# embeddings_queue

created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: ffed9d9d-0729-4988-a1e4-d3e279d96bf6
encoding: FLOAT32
metadata:
{"original_content": "Diagnosis is usually based on thyroid function and imaging test findings (see p.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 51, "type": "hypothetical_questions", "chroma:document": "1. What are the common symptoms associated with thyroid dysfunction due to nutritional disorders?\n2. How can dietary deficiencies contribute to the development of thyroid-related health conditions?\n3. What imaging tests are typically used to diagnose nutritional disorders affecting thyroid function?\n4. What dietary changes can help manage symptoms of thyroid disorders linked to nutritional imbalances?\n5. How do metabolic disorders influence the effectiveness of certain vitamins and minerals in the body?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 8fdf66c9-132a-4dc2-adcc-0710a5c6f5a7
encoding: FLOAT32
metadata:
{"original_content": "776\n), which are\ncorrelated with clinical data. Iodine excretion may be more specific but is not usually measured.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 51, "type": "hypothetical_questions", "chroma:document": "1. What are the common symptoms associated with iodine deficiency in individuals?\n2. How can iodine excretion levels be correlated with clinical data in diagnosing nutritional disorders?\n3. What dietary changes can help prevent iodine deficiency and its related health issues?\n4. What are the potential health consequences of long-term iodine deficiency?\n5. How does iodine deficiency affect metabolic processes in the body?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: e46fa521-a3cb-4c2e-8060-ae87210e2c49
encoding: FLOAT32
metadata:
{"original_content": "Treatment\nconsists of correcting thyroid abnormalities and, if intake is excessive, dietary modification. Iron\nIron (Fe) is a component of hemoglobin, myoglobin, and many enzymes in the body.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 51, "type": "hypothetical_questions", "chroma:document": "1. What are the symptoms of iron deficiency anemia and how can it be treated?\n2. How does excessive iron intake affect thyroid function and what dietary modifications are recommended?\n3. What role does iron play in the body, and how can its deficiency impact overall health?\n4. What are the common causes of iron deficiency and how can they be addressed through diet?\n5. How can correcting thyroid abnormalities improve symptoms associated with iron deficiency?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: f106eaf9-a711-4333-b7c0-9f70ee1aa82f
encoding: FLOAT32
metadata:
{"original_content": "Heme iron, contained\nmainly in animal products, is absorbed much better than nonheme iron (eg, in plants and grains), which\naccounts for > 85% of iron in the average diet. However, absorption of nonheme iron is increased when it\nis consumed with animal protein and vitamin C. Deficiency:\n Iron deficiency is one of the most common mineral deficiencies in the world. It may result\nfrom the following:\n\u2022 Inadequate iron intake, common in infants, adolescent girls, and pregnant women\n\u2022 Malabsorption (eg, celiac sprue)\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n104", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 51, "type": "hypothetical_questions", "chroma:document": "1. What are the primary dietary sources of heme iron and nonheme iron, and how do they differ in absorption rates?\n2. What are the common symptoms associated with iron deficiency, and who is most at risk for developing this condition?\n3. How does the presence of vitamin C and animal protein influence the absorption of nonheme iron in the diet?\n4. What are some underlying health conditions that can lead to malabsorption of iron, such as celiac sprue?\n5. What dietary changes or supplements can be recommended to address iron deficiency in at-risk populations like pregnant women and adolescent girls?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 946caa34-0219-4e61-bb49-a3584d1cf1eb
encoding: FLOAT32
metadata:
{"original_content": "\u2022 Chronic bleeding\nChronic bleeding due to colon cancer is a serious cause in middle-aged people and the elderly. When deficiency is advanced, microcytic anemia develops (see p.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 52, "type": "hypothetical_questions", "chroma:document": "1. What are the nutritional implications of chronic bleeding due to colon cancer in middle-aged and elderly individuals?\n2. How does chronic bleeding lead to microcytic anemia, and what are the symptoms associated with this condition?\n3. What dietary changes can be implemented to address deficiencies caused by chronic bleeding?\n4. What are the potential treatments for microcytic anemia resulting from chronic bleeding?\n5. How can early detection of chronic bleeding impact nutritional health and overall treatment outcomes?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 29b898cf-dbf9-40ab-80d0-affc680112c6
encoding: FLOAT32
metadata:
{"original_content": "924\n). In addition to anemia, iron deficiency may cause pica (a craving for nonfoods) and spoon nails and is\nassociated with restless leg syndrome. Rarely, iron deficiency causes dysphagia due to postcricoid\nesophageal web. Diagnosis involves CBC, serum ferritin, and possibly measurement of transferrin saturation (iron\ncapacity).", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 52, "type": "hypothetical_questions", "chroma:document": "1. What are the common symptoms associated with iron deficiency anemia?\n2. How can pica be related to iron deficiency, and what does it entail?\n3. What diagnostic tests are used to confirm iron deficiency in patients?\n4. What are the potential complications of untreated iron deficiency, such as dysphagia?\n5. How does iron deficiency relate to conditions like restless leg syndrome?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: daa670db-c220-4105-a9bf-fdad2adca00e
encoding: FLOAT32
metadata:
{"original_content": "All people with moderate or severe iron deficiency and some people with mild deficiency require iron\nsupplementation. Toxicity:\n Iron may accumulate in the body because of\n\u2022 Iron therapy given in excessive amounts or for too long\n\u2022 Repeated blood transfusions\n\u2022 Chronic alcoholism\n\u2022 Overdose of iron\nIron overload can also result from an inherited iron overload disease (hemochromatosis\u2014see p. 1032\n), a\npotentially fatal but easily treatable genetic disorder in which too much iron is absorbed. Hemochromatosis affects > 1 million Americans. An overdose of iron is toxic (see p. 3341\n), causing vomiting, diarrhea, and damage to the intestine and\nother organs. Diagnosis is similar to that for iron deficiency.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 52, "type": "hypothetical_questions", "chroma:document": "1. What are the potential causes of iron overload in the body?\n2. What symptoms might indicate an iron overdose?\n3. How can chronic alcoholism contribute to iron toxicity?\n4. What treatment options are available for individuals diagnosed with hemochromatosis?\n5. How does the body typically respond to excessive iron supplementation?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 852a4076-e7b9-425f-b6d0-9fa73d179f5e
encoding: FLOAT32
metadata:
{"original_content": "Treatment often involves deferoxamine, which binds with iron and is excreted in urine. Manganese\nManganese (Mn), necessary for healthy bone structure, is a component of several enzyme systems,\nincluding manganese-specific glycosyltransferases and phosphoenolpyruvate carboxykinase. Median\nintake is between 1.6 and 2.3 mg/day; absorption is 5 to 10%.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 52, "type": "hypothetical_questions", "chroma:document": "1. What role does manganese play in the body's enzyme systems and overall health?\n2. What are the symptoms of manganese deficiency?\n3. How does deferoxamine treatment help in managing iron overload conditions?\n4. What is the recommended daily intake of manganese for adults?\n5. What are the potential health risks associated with excessive manganese intake?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: bf4c8d29-da9f-4e76-a309-4b5b1c55ee6c
encoding: FLOAT32
metadata:
{"original_content": "Deficiency has not been conclusively documented, although one experimental case in a volunteer\nresulted in transient dermatitis, hypocholesterolemia, and increased alkaline phosphatase levels. Toxicity is usually limited to people who mine and refine ore; prolonged exposure causes neurologic\nsymptoms resembling those of parkinsonism or Wilson's disease. Molybdenum\nMolybdenum (Mo) is a component of coenzymes necessary for the activity of xanthine oxidase, sulfite\noxidase, and aldehyde oxidase. Genetic and nutritional deficiencies of molybdenum have been reported but are rare. Genetic sulfite\noxidase deficiency was described in 1967 in a child. It resulted from the inability to form the molybdenum\ncoenzyme despite the presence of adequate molybdenum. The deficiency caused intellectual disability,\nseizures, opisthotonus, and lens dislocation. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 52, "type": "hypothetical_questions", "chroma:document": "1. What are the potential symptoms associated with molybdenum deficiency?\n2. How does prolonged exposure to molybdenum affect neurological health?\n3. What coenzymes require molybdenum for their activity, and what role do they play in metabolism?\n4. Can genetic factors contribute to molybdenum deficiency, and if so, how?\n5. What are the treatment options for individuals with genetic sulfite oxidase deficiency associated with molybdenum?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 08fa8f8e-b4d3-4339-9289-7fd8ba8ca8dc
encoding: FLOAT32
metadata:
{"original_content": "Mineral Deficiency & Toxicity\n105", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 52, "type": "hypothetical_questions", "chroma:document": "1. What are the symptoms associated with a deficiency in essential minerals such as zinc or magnesium?  \n2. How can mineral toxicity affect overall health and what are its common symptoms?  \n3. What dietary changes can help prevent mineral deficiencies in populations at risk?  \n4. What are the primary causes of vitamin and mineral imbalances in children and adults?  \n5. How do metabolic disorders influence the body's ability to absorb essential nutrients?  "}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: b2c2a736-a706-4575-99e3-381647639ce4
encoding: FLOAT32
metadata:
{"original_content": "Molybdenum deficiency resulting in sulfite toxicity occurred in a patient receiving long-term TPN. Symptoms were tachycardia, tachypnea, headache, nausea, vomiting, and coma. Laboratory tests\nshowed high levels of sulfite and xanthine and low levels of sulfate and uric acid in the blood and urine. Ammonium molybdate 300 \n\u03bc\ng/day IV caused dramatic recovery. A case of molybdenum toxicity may have occurred in 1961; it caused goutlike symptoms and\nabnormalities of the GI tract, liver, and kidneys. Selenium\nSelenium (Se) is a part of the enzyme glutathione peroxidase, which metabolizes hydro-peroxides formed\nfrom polyunsaturated fatty acids.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "type": "hypothetical_questions", "chroma:document": "1. What are the symptoms associated with molybdenum deficiency and sulfite toxicity in patients on long-term TPN?\n2. How can high levels of sulfite and low levels of sulfate in the blood indicate a molybdenum deficiency?\n3. What treatment options are available for patients suffering from molybdenum deficiency?\n4. Can selenium deficiency impact the metabolism of polyunsaturated fatty acids, and if so, how?\n5. What were the clinical manifestations of molybdenum toxicity reported in the 1961 case?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: b6e1f8d6-39c4-46f1-bbc6-86f107117296
encoding: FLOAT32
metadata:
{"original_content": "Selenium is also a part of the enzymes that deiodinate thyroid\nhormones. Generally, selenium acts as an antioxidant that works with vitamin E. Some epidemiologic\nstudies associate low selenium levels with cancer. In children with Down syndrome, selenium\nsupplements may help prevent bacterial infections. Plasma levels vary from 8 to 25 \n\u03bc\ng/dL, depending on\nselenium intake.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "type": "hypothetical_questions", "chroma:document": "1. What role does selenium play in the metabolism of thyroid hormones?\n2. How might low selenium levels be associated with cancer risk?\n3. In what ways can selenium supplements benefit children with Down syndrome?\n4. What are the typical plasma selenium levels, and how do they relate to dietary intake?\n5. How does selenium interact with vitamin E in the body?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: b5675988-0096-4243-b91f-cbd8c335d2a0
encoding: FLOAT32
metadata:
{"original_content": "Diagnosis is usually clinical; sometimes blood glutathione peroxidase is measured. Deficiency:\n Deficiency is rare, even in New Zealand and Finland, where selenium intake \nis 30 to 50\n\u03bc\ng/day, compared with 100 to 250 \n\u03bc\ng/day in the US and Canada. In certain areas of China, where intake\naverages 10 to 15 \n\u03bc\ng/day, selenium deficiency predisposes patients to Keshan disease, an endemic viral\ncardiomyopathy affecting primarily children and young women. This cardiomyopathy can be prevented\nbut not cured by sodium selenite supplements of 50 \n\u03bc\ng/day po. Patients receiving long-term TPN have\ndeveloped selenium deficiency with muscle pain and tenderness that responded to a selenomethionine\nsupplement. In Siberian Russia and China, growing children with selenium deficiency may develop\nchronic osteoarthropathy (Kashin-Beck disease).", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "type": "hypothetical_questions", "chroma:document": "1. What are the clinical symptoms associated with selenium deficiency?\n2. How does selenium deficiency lead to the development of Keshan disease?\n3. What dietary sources can help prevent selenium deficiency?\n4. What is the recommended treatment for individuals experiencing selenium deficiency related to long-term TPN?\n5. In what regions are children particularly at risk for chronic osteoarthropathy due to selenium deficiency?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: aa3df3a0-fb68-4139-8dca-7b7bfd5d5aa5
encoding: FLOAT32
metadata:
{"original_content": "Selenium deficiency may contribute synergistically with\niodine deficiency to the development of goiter and hypothyroidism. Diagnosis is made clinically or sometimes by measuring glutathione peroxidase activity or plasma\nselenium, but neither of these tests is readily available.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "type": "hypothetical_questions", "chroma:document": "1. How does selenium deficiency interact with iodine deficiency in relation to thyroid health?\n2. What clinical symptoms might indicate a deficiency in selenium or iodine?\n3. What methods are available for diagnosing selenium deficiency, despite the challenges in testing?\n4. What role does glutathione peroxidase activity play in assessing selenium levels?\n5. What are the potential health consequences of untreated goiter and hypothyroidism related to nutrient deficiencies?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 21469e91-47ef-4870-9aa9-69ba33734965
encoding: FLOAT32
metadata:
{"original_content": "Treatment consists of sodium selenite 100 \n\u03bc\ng/day\npo. Toxicity:\n At high doses (> 900 \n\u03bc\ng/day), selenium causes toxicity. Manifestations include hair loss,\nabnormal nails, dermatitis, peripheral neuropathy, nausea, diarrhea, fatigue, irritability, and a garlic odor of\nthe breath. Toxic levels of plasma selenium are not well defined. Zinc\nZinc (Zn) is contained mainly in bones, teeth, hair, skin, liver, muscle, leukocytes, and testes. Zinc is a\ncomponent of several hundred enzymes, including many nicotinamide adenine dinucleotide (NADH)\ndehydrogenases, RNA and DNA polymerases, and DNA transcription factors as well as alkaline\nphosphatase, superoxide dismutase, and carbonic anhydrase. A diet high in fiber and phytate (eg, in\nwhole-grain bread) reduces zinc absorption.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "type": "hypothetical_questions", "chroma:document": "1. What are the symptoms of selenium toxicity and at what dosage does it typically occur?\n2. How does a high-fiber diet impact zinc absorption in the body?\n3. What are the primary functions of zinc in human metabolism?\n4. What dietary sources are high in selenium and how can they be incorporated into a daily diet?\n5. What role does zinc play in enzyme function and why is it crucial for overall health?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 78844fda-12a4-4157-a963-6ee766c6e8fc
encoding: FLOAT32
metadata:
{"original_content": "Deficiency:\n Dietary deficiency is unlikely in healthy people. Secondary zinc deficiency can develop in the\nfollowing:\n\u2022 Some patients with hepatic insufficiency (because the ability to retain zinc is lost)\n\u2022 Patients taking diuretics\n\u2022 Patients with diabetes mellitus, sickle cell disease, chronic renal failure, or malabsorption\n\u2022 Patients with stressful conditions (eg, sepsis, burns, head injury)\n\u2022 Elderly institutionalized and homebound patients (common)\nMaternal zinc deficiency may cause fetal malformations and low birth weight. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "type": "hypothetical_questions", "chroma:document": "1. What are the potential causes of secondary zinc deficiency in patients with chronic renal failure?\n2. How can maternal zinc deficiency impact fetal development during pregnancy?\n3. What role do diuretics play in the development of zinc deficiency in patients?\n4. Which populations are most at risk for developing zinc deficiency due to stressful conditions?\n5. How does hepatic insufficiency contribute to the loss of zinc retention in the body?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: d2ef4e5f-ed3c-44bf-959e-b17b3aa1d07d
encoding: FLOAT32
metadata:
{"original_content": "Mineral Deficiency & Toxicity\n106", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "type": "hypothetical_questions", "chroma:document": "1. What are the common symptoms associated with mineral deficiencies, and how can they impact overall health?\n2. What dietary changes can help prevent mineral toxicity and its associated health complications?\n3. How do specific vitamin and mineral imbalances contribute to the development of metabolic disorders?\n4. What are the underlying causes of obesity related to nutritional disorders, and how can they be addressed?\n5. What treatment options are available for individuals suffering from mineral deficiencies or toxicities?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: a7eccf7b-b94b-4643-b8b2-1ceaf4b7374f
encoding: FLOAT32
metadata:
{"original_content": "Zinc deficiency in children causes impaired growth and impaired taste (hypogeusia). Other symptoms and\nsigns in children include delayed sexual maturation and hypogonadism. In children or adults, symptoms\ninclude hypogonadism, alopecia, impaired immunity, anorexia, dermatitis, night blindness, anemia,\nlethargy, and impaired wound healing. Zinc deficiency should be suspected in undernourished patients with typical symptoms or signs. However,\nbecause many of the symptoms and signs are nonspecific, clinical diagnosis of mild zinc deficiency is\ndifficult. Laboratory diagnosis is also difficult. Low albumin levels, common in zinc deficiency, make serum\nzinc levels difficult to interpret; diagnosis usually requires the combination of low levels of zinc in serum\nand increased urinary zinc excretion. If available, isotope studies can measure zinc status more\naccurately.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 54, "type": "hypothetical_questions", "chroma:document": "1. What are the primary symptoms of zinc deficiency in children?\n2. How can zinc deficiency impact growth and sexual maturation in children?\n3. What laboratory tests are most effective in diagnosing zinc deficiency?\n4. What are the potential consequences of zinc deficiency on immune function?\n5. How can dietary changes help prevent or treat zinc deficiency in undernourished patients?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 9885bc8b-227c-4b9f-b550-7f12040fb200
encoding: FLOAT32
metadata:
{"original_content": "Treatment consists of elemental zinc 15 to 120 mg/day po until symptoms and signs resolve. Acrodermatitis enteropathica\n (a rare, once fatal autosomal recessive disorder) causes malabsorption\nof zinc. Psoriasiform dermatitis develops around the eyes, nose, and mouth; on the buttocks; and in an\nacral distribution. The disorder also causes hair loss, paronychia, impaired immunity, recurrent infection,\nimpaired growth, and diarrhea.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 54, "type": "hypothetical_questions", "chroma:document": "1. What are the key symptoms of acrodermatitis enteropathica related to zinc deficiency?  \n2. How does acrodermatitis enteropathica affect the immune system?  \n3. What is the recommended dosage of elemental zinc for treating acrodermatitis enteropathica?  \n4. Can acrodermatitis enteropathica lead to growth impairments in children?  \n5. What are the potential complications of untreated zinc malabsorption disorders?  "}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: bbfd8a95-5572-4093-afc6-0ce48cbf5591
encoding: FLOAT32
metadata:
{"original_content": "Symptoms and signs usually develop after infants are weaned from breast\nmilk.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 54, "type": "hypothetical_questions", "chroma:document": "1. What nutritional disorder is commonly associated with symptoms developing after weaning from breast milk in infants?\n2. What are the potential dietary deficiencies that can arise in infants who are weaned too early from breast milk?\n3. How do the signs and symptoms of nutritional disorders manifest in infants following the cessation of breastfeeding?\n4. What treatments are recommended for infants experiencing nutritional disorders after weaning from breast milk?\n5. What are the long-term health implications of not addressing nutritional deficiencies in infants after they are weaned from breast milk?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 1a027c10-e74c-4c29-8191-5925619e0721
encoding: FLOAT32
metadata:
{"original_content": "In such cases, doctors suspect the diagnosis. If deficiency is diagnosed, zinc sulfate 30 to 150\nmg/day po usually results in complete remission. Toxicity:\n The recommended upper limit for zinc intake is 40 mg/day. Toxicity is rare. Ingesting doses of\nelemental zinc ranging from 100 to 150 mg/day for prolonged periods interferes with copper metabolism\nand causes low blood copper levels, RBC microcytosis, neutropenia, and impaired immunity; higher\ndoses should be given only for short periods of time and the patient should be followed closely. Ingesting\nlarger amounts (200 to 800 mg/day), usually by consuming acidic food or drink from a galvanized (zinc-\ncoated) container, can cause anorexia, vomiting, and diarrhea. Metal fume fever, also called brass-\nfounders' ague or zinc shakes, is caused by inhaling industrial zinc oxide fumes; it results in neurologic\ndamage. Symptoms usually resolve after 12 to 24 h in a zinc-free environment.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 54, "type": "hypothetical_questions", "chroma:document": "1. What are the symptoms of zinc deficiency and how is it diagnosed?\n2. What is the recommended daily intake of zinc for adults, and what are the potential consequences of exceeding this limit?\n3. How does prolonged high intake of zinc affect copper metabolism and what are the resulting health issues?\n4. What are the signs and symptoms of zinc toxicity, and what immediate actions should be taken if they occur?\n5. What is metal fume fever, and what are the potential long-term effects of exposure to zinc oxide fumes?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: 0f770c91-7a29-490d-a574-805688656214
encoding: FLOAT32
metadata:
{"original_content": "The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 54, "type": "hypothetical_questions", "chroma:document": "1. What are the common symptoms associated with vitamin D deficiency and how can it be treated?\n2. What dietary changes can help manage metabolic syndrome effectively?\n3. What are the primary causes of iron deficiency anemia and what are the recommended interventions?\n4. How does obesity affect the risk of developing nutritional disorders, and what strategies can be implemented for weight management?\n5. What are the signs of malnutrition in children and what nutritional interventions are recommended?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: f2238a39-87a9-41fe-bc63-21d2460dcc75
encoding: FLOAT32
metadata:
{"original_content": "Mineral Deficiency & Toxicity\n107", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 54, "type": "hypothetical_questions", "chroma:document": "1. What are the common symptoms associated with mineral deficiencies in adults?\n2. How can mineral toxicity affect overall health and what are its potential consequences?\n3. What dietary changes can help prevent mineral deficiencies in at-risk populations?\n4. What are the primary causes of vitamin and mineral imbalances in individuals with obesity?\n5. What treatments are available for addressing specific mineral deficiencies and their associated health issues?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: bedd2d95-e26c-4ac5-850a-123db0ba954c
encoding: FLOAT32
metadata:
{"original_content": "Chapter 6. Obesity and the Metabolic Syndrome\nObesity\nObesity is excess body fat; consequences depend not only on the absolute amount but also on\nthe distribution of the fat. Complications include cardiovascular disorders, diabetes mellitus,\nmany cancers, cholelithiasis, fatty liver and cirrhosis, osteoarthritis, reproductive disorders in\nmen and women, psychologic disorders, and premature death.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "type": "hypothetical_questions", "chroma:document": "1. What are the health complications associated with obesity beyond cardiovascular disorders and diabetes mellitus?\n2. How does the distribution of body fat influence the severity of obesity-related health issues?\n3. What psychological disorders are commonly linked to obesity, and how do they manifest in affected individuals?\n4. What dietary changes can help mitigate the risk of developing metabolic syndrome in obese individuals?\n5. How can obesity lead to reproductive disorders in both men and women?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
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{"original_content": "Diagnosis is based on body\nmass index (BMI\u2014calculated from height and weight) and waist circumference. BP, fasting\nplasma glucose, and lipid levels should be measured. Treatment includes physical activity,\ndietary and behavioral modification, and sometimes drugs or surgery.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "type": "hypothetical_questions", "chroma:document": "1. What measurements are used to diagnose nutritional disorders related to body composition and metabolic health?\n2. How can lifestyle modifications, such as diet and exercise, impact the treatment of obesity-related nutritional disorders?\n3. What role do BP, fasting plasma glucose, and lipid levels play in assessing nutritional disorders?\n4. In what cases might medication or surgery be necessary for treating nutritional disorders?\n5. What are the potential consequences of untreated nutritional disorders on overall health?"}


created_at: 2025-08-16 05:08:50
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{"original_content": "Prevalence of obesity in the US is high and is increasing, particularly among children and adolescents\n(see\nTable 6-1\n). Prevalence is more than twice as high at age 55 as at age 20. Obesity is twice as common among women\nin a lower socioeconomic group as among those in a higher group. Prevalence among black and white\nmen does not differ significantly, but it is higher among black women than white women. More than 50%\nof black women \u2265 40 yr are obese; > 80% are overweight. In the US, obesity and its complications cause as many as 300,000 premature deaths each year, making\nit second only to cigarette smoking as a preventable cause of death.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "type": "hypothetical_questions", "chroma:document": "1. What demographic factors contribute to the higher prevalence of obesity among women in lower socioeconomic groups compared to those in higher groups?\n2. How does the prevalence of obesity differ between black women and white women in the US?\n3. What are the health complications associated with obesity that lead to premature deaths in the US?\n4. At what age does the prevalence of obesity significantly increase, particularly in the context of children and adolescents?\n5. What measures can be taken to reduce obesity rates among populations most at risk, such as black women over 40 years old?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
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{"original_content": "[\nTable 6-1. Changes in Prevalence of Obesity According to Nhanes]\nEtiology\nAlmost all cases of obesity result from a combination of genetic predisposition and a chronic imbalance\nbetween energy intake, energy utilization for basic metabolic processes, and energy expenditure from\nphysical activity. Genetic factors:\n Heritability of BMI is about 66%. Genetic factors may affect the many signaling\nmolecules and receptors used by parts of the hypothalamus and GI tract to regulate food intake (see\nSidebar 6-1\n). Rarely, obesity results from abnormal levels of peptides that regulate food intake (eg, leptin)\nor abnormalities in their receptors (eg, melanocortin-4 receptor). Genetic factors also regulate energy expenditure, including BMR, diet-induced thermogenesis, and\nnonvoluntary activity-associated thermogenesis. Genetic factors may have a greater effect on the\ndistribution of body fat, particularly abdominal fat (see \nMetabolic Syndrome\n on p. 64\n), than on the amount\nof body fat.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "type": "hypothetical_questions", "chroma:document": "1. What role do genetic factors play in the development of obesity and its prevalence in the population?\n2. How does the heritability of Body Mass Index (BMI) influence individual risk for obesity?\n3. What are the signaling molecules involved in regulating food intake, and how can genetic factors affect their function?\n4. In what ways do genetic predispositions affect the distribution of body fat, particularly in relation to metabolic syndrome?\n5. How do abnormalities in peptides like leptin or their receptors contribute to obesity in rare cases?"}


created_at: 2025-08-16 05:08:50
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: baef533c-182b-4554-aa69-c4fc2c56e3ac
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{"original_content": "Environmental factors:\n Weight is gained when caloric intake exceeds energy needs. Important\ndeterminants of energy intake include portion sizes and the energy density of the food. High-fat foods,\nprocessed foods, and diets high in refined carbohydrates, soft drinks, fruit juices, and alcohol promote\nweight gain. Diets high in fresh fruit and vegetables, fiber, and complex carbohydrates, with water as the\nmain fluid consumed, minimize weight gain. A sedentary lifestyle promotes weight gain. Regulatory factors:\n Prenatal maternal obesity, prenatal maternal smoking, intrauterine growth\nrestriction, and insufficient sleep can disturb weight regulation. About 15% of women permanently gain \u2265\n20 lb with each pregnancy.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "type": "hypothetical_questions", "chroma:document": "1. What role do portion sizes play in the regulation of caloric intake and weight management?\n2. How does a diet high in processed foods contribute to weight gain compared to a diet rich in fresh fruits and vegetables?\n3. What environmental factors are associated with the development of obesity during and after pregnancy?\n4. How does a sedentary lifestyle impact energy balance and weight gain?\n5. In what ways can prenatal maternal obesity influence weight regulation in offspring?"}


created_at: 2025-08-16 05:08:51
topic: persistent://default/default/c7b40b83-87aa-4ab1-9a82-e92325faba56
id: d5448050-6869-4285-bec7-8f85844d83fd
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{"original_content": "Obesity that persists beyond early childhood makes weight loss in later life\nmore difficult. Drugs, including corticosteroids, lithium, traditional antidepressants (tricyclics, tetracyclics, and\nmonoamine oxidase inhibitors [MAOIs]), benzodiazepines, and antipsychotic drugs, often cause weight\ngain. Uncommonly, weight gain is caused by one of the following disorders:\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 6.", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "type": "hypothetical_questions", "chroma:document": "1. What are the common medications that can contribute to weight gain in individuals with obesity?\n2. How does obesity in early childhood affect weight loss efforts later in life?\n3. What are some uncommon medical disorders that can lead to weight gain?\n4. What role do corticosteroids play in causing weight gain, and what alternatives exist for managing their side effects?\n5. How can individuals manage weight gain associated with traditional antidepressant medications?"}


created_at: 2025-08-16 05:08:51
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{"original_content": "Obesity & the Metabolic Syndrome\n108", "source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "type": "hypothetical_questions", "chroma:document": "1. What are the primary causes of obesity and how do they contribute to the development of metabolic syndrome?\n2. What dietary changes can help individuals with metabolic syndrome manage their symptoms effectively?\n3. What are the common symptoms associated with obesity and metabolic syndrome?\n4. How does a deficiency in specific vitamins and minerals influence the risk of developing obesity?\n5. What treatment options are available for individuals diagnosed with metabolic syndrome?"}


created_at: 2025-08-16 05:09:01
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{"original_content": "[['Food', 'Glycemic Index'], ['Glucose', '100'], ['Sucrose', '65'], ['Starches', 'Variable'], ['Fiber', '0']]", "source": "Nutritional Disorders.pdf", "page": 1, "type": "hypothetical_table_question", "chroma:document": "1. How does the glycemic index of different foods impact blood sugar levels in individuals with diabetes?\n2. What are the potential health risks associated with consuming high-glycemic index foods like glucose and sucrose?\n3. In what ways can dietary fiber intake influence metabolic disorders and obesity?\n4. How can understanding the glycemic index of starches help in managing weight loss or dietary plans for those with nutritional disorders?\n5. What role does glycemic index play in the treatment and prevention of conditions related to vitamin and mineral imbalances?"}


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created_at: 2025-08-16 05:09:01
topic: persistent://default/default/6685475d-ceaa-4f8f-ae89-b8696fb1e1d8
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{"original_content": "[['Inadequate absorption', 'Decreased acid secretion in the elderly'], ['Blind loop syndrome', 'Overgrowth of bacteria'], ['Fish tapeworm infestation', 'Bacteria or parasites use ingested vitamin B12'], ['Ileal absorptive site destruction', 'Inflammatory bowel disease'], ['Surgical removal of ileum', ''], ['Chronic pancreatitis', ''], ['Gastric surgery', ''], ['Malabsorption syndromes', ''], ['AIDS', ''], ['Use of certain drugs', '(e.g., antacids, metformin)'], ['Repeated exposure to nitrous oxide', ''], ['Genetic disorder', 'Imerslund-Graesbeck syndrome']]", "source": "Nutritional Disorders.pdf", "page": 35, "type": "hypothetical_table_question", "chroma:document": "1. What are the potential causes of vitamin B12 deficiency in individuals with gastrointestinal issues?\n2. How does chronic pancreatitis impact nutrient absorption and lead to nutritional disorders?\n3. What role does bacterial overgrowth play in malabsorption syndromes, and what are the implications for treatment?\n4. How can surgical removal of the ileum affect vitamin and mineral absorption in patients?\n5. What are the effects of certain medications, such as metformin, on nutrient absorption and dietary deficiencies?"}


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1 - Nutritional Disorders
Chapter 1. Nutrition: General Considerations
Introduction
Nutrition is the science of food and its relationship to health. Nutrients are chemicals in foods that are
used by the body for growth, maintenance, and energy.


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Nutrients that cannot be synthesized by the body
and thus must be derived from the diet are considered essential. They include vitamins, minerals, some
amino acids, and some fatty acids. Nutrients that the body can synthesize from other compounds,
although they may also be derived from the diet, are considered nonessential. Macronutrients are
required by the body in relatively large amounts; micronutrients are needed in minute amounts. Lack of nutrients can result in deficiency syndromes (eg, kwashiorkor, pellagra) or other disorders (see p.


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9
). Excess intake of macronutrients can lead to obesity (see p. 56
) and related disorders; excess intake of
micro-nutrients can be toxic. Also, the balance of various types of nutrients, such as how much
usaturated vs saturated fat is consumed, can influence the development of disorders. Macronutrients
Macronutrients constitute the bulk of the diet and supply energy and many essential nutrients. Carbohydrates, proteins (including essential amino acids), fats (including essential fatty acids),
macrominerals, and water are macronutrients. Carbohydrates, fats, and proteins are interchangeable as
sources of energy; fats yield 9 kcal/g (37.8 kJ/g); proteins and carbohydrates yield 4 kcal/g (16.8 kJ/g). Carbohydrates:
 Dietary carbohydrates are broken down into glucose and other monosaccharides.


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Carbohydrates increase blood glucose levels, supplying energy. Simple carbohydrates are composed of
small molecules, generally monosaccharides or disaccharides, which increase blood glucose levels
rapidly. Complex carbohydrates are composed of larger molecules, which are broken down into
monosaccharides. Complex carbohydrates increase blood glucose levels more slowly but for a longer
time. Glucose and sucrose are simple carbohydrates; starches and fiber are complex carbohydrates. The glycemic index measures how rapidly consumption of a carbohydrate increases plasma glucose
levels. Values range from 1 (the slowest increase) to 100 (the fastest increase, equivalent to pure glucose
—see
Table 1-1
). However, the actual rate of increase also depends on what foods are consumed with the
carbohydrate.


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Carbohydrates with a high glycemic index may increase plasma glucose to high levels rapidly. It is
hypothesized that, as a result, insulin levels increase, inducing hypoglycemia and hunger, which tends to
lead to consumption of excess calories and weight gain. Carbohydrates with a low glycemic index
increase plasma glucose levels slowly, resulting in lower postprandial insulin levels and less hunger,
which probably makes consumption of excess calories less likely. These effects are predicted to result in
a more favorable lipid profile and a decreased risk of obesity, diabetes mellitus, and complications of
diabetes if present.


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Proteins are required for
tissue maintenance, replacement, function, and growth. However, if the body is not getting enough
calories from dietary sources or tissue stores (particularly of fat), protein may be used for energy. As the body uses dietary protein for tissue production, there is a net gain of protein (positive nitrogen
balance). During catabolic
[
Table 1-1. Glycemic Index of Some Foods]
states (eg, starvation, infections, burns), more protein may be used (because body tissues are broken
down) than is absorbed, resulting in a net loss of protein (negative nitrogen balance). Nitrogen balance is
best determined by subtracting the amount of nitrogen excreted in urine and feces from the amount of
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1.


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nitrogen consumed. Of the 20 amino acids, 9 are essential amino acids (EAAs); they cannot be synthesized and must be
obtained from the diet. All people require 8 EAAs; infants also require histidine. The weight-adjusted requirement for dietary protein correlates with growth rate, which decreases from
infancy until adulthood. The daily dietary protein requirement decreases from 2.2 g/kg in 3-mo-old infants
to 1.2 g/kg in 5-yr-old children and to 0.8 g/kg in adults. Protein requirements correspond to EAA
requirements (see
Table 1-2
).


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Adults trying to increase muscle mass need very little extra protein beyond the requirements in
the table.


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The amino acid composition of protein varies widely. Biological value (BV) reflects the similarity in amino
acid composition of protein to that of animal tissues; thus, BV indicates what percentage of a dietary
protein provides EAAs for the body. A perfect match is egg protein, with a value of 100. Animal proteins in
milk and meat have a high BV (~90); proteins in cereal and vegetables have a lower BV (~40), and some
derived proteins (eg, gelatin) have a BV of 0. The extent to which dietary proteins supply each other's
missing amino acids (complementarity) determines the overall BV of the diet. The recommended daily
allowances (RDA) for protein assumes that the average mixed diet has a BV of 70. Fats:
 Fats are broken down into fatty acids and glycerol.


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Fats are required for tissue growth and hormone
production. Saturated fatty acids, common in animal fats, tend to be solid at room temperature. Except for
palm and coconut oils, fats derived from plants tend to be liquid at room temperature; these fats contain
high levels of monounsaturated fatty acids or polyunsaturated fatty acids (PUFAs). Partial hydrogenation of unsaturated fatty acids (as occurs during food manufacturing) produces trans
fatty acids, which are solid or semisolid at room temperature. In the US, the main dietary source of trans
fatty acids is partially hydrogenated vegetable oils, used in manufacturing certain foods (eg, cookies,
crackers, chips) to prolong shelf-life. Trans fatty acids may elevate LDL cholesterol and lower HDL; they
may also independently increase the risk of coronary artery disease. Essential fatty acids (EFAs) are linoleic acid, an 
ω
-6 (n-6) fatty acid, and linolenic acid, an 
ω
-3 (n-3) fatty
acid. Other 
ω
-6 acids (eg, arachidonic acid) and other 
ω
-3 fatty acids (eg, eicosapentaenoic acid,
docosahexaenoic acid) are required by the body but can be synthesized from EFAs. EFAs (see also p. 19
) are needed for the formation of various eicosanoids (biologically active lipids),
including prostaglandins, thromboxanes, prostacyclins, and leukotrienes. Consumption of 
ω
-3 fatty acids
may decrease the risk of coronary artery disease.


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Essential Amino Acid Requirements in mg/kg Body Weight]
Requirements for EFAs vary by age. Adults require amounts of linoleic acid equal to at least 2% of total
caloric needs and linolenic acid equal to at least 0.5%. Vegetable oils provide linoleic acid and linolenic
acid. Oils made from safflower, sunflower, corn, soya, primrose, pumpkin, and wheat germ provide large
amounts of linoleic acid. Marine fish oils and oils made from flax-seeds, pumpkin, soy, and canola provide
large amounts of linolenic acid. Marine fish oils also provide some other 
ω
-3 fatty acids in large amounts. Macrominerals:
 Na, Cl, K, Ca, P, and Mg are required in relatively large amounts per day (see
Tables 1-3
,
1-4
, and
5-2
).


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Water:
 Water is considered a macronutrient because it is required in amounts of 1 mL/kcal (0.24 mL/kJ)
of energy expended, or about 2500 mL/day. Needs vary with fever, physical activity, and changes in
climate and humidity.


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Macrominerals]
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations
54


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[
Table 1-4. Recommended Dietary Reference Intakes* for Some Macronutrients, Food and Nutrition
Board, Institute of Medicine of the National Academies]
Micronutrients
Vitamins and minerals required in minute amounts (trace minerals) are micronutrients (see 
Chs. 4
 and 
5
).


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Water-soluble vitamins
 are vitamin C (ascorbic acid) and 8 members of the vitamin B complex: biotin,
folate, niacin, pantothenic acid, riboflavin (vitamin B
2
), thiamin (vitamin B
1
), vitamin B
6
 (pyridoxine), and
vitamin B
12
 (cobalamin). Fat-soluble vitamins
 are vitamins A (retinol), D (cholecalciferol and ergocalciferol), E (
α
-tocopherol), and
K (phylloquinone and menaquinone). Only vitamins A, E, and B
12
 are stored to any significant extent in the body; the other vitamins must be
consumed regularly to maintain tissue health. Essential trace minerals
 include chromium, copper, iodine, iron, manganese, molybdenum, selenium,
and zinc. Except for chromium, each of these is incorporated into enzymes or hormones required in
metabolism. Except for deficiencies of iron and zinc, micromineral deficiencies are uncommon in
developed countries (see 
Ch. 5
).


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Other minerals (eg, aluminum, arsenic, boron, cobalt, fluoride, nickel, silicon, vanadium) have not been
proved essential for people. Fluoride, although not essential, helps prevent tooth decay by forming a
compound with Ca (CaF
2
), which stabilizes the mineral matrix in teeth. All trace minerals are toxic at high levels, and some (arsenic, nickel, and chromium) may cause cancer. Other Dietary Substances
The daily human diet typically contains as many as 100,000 chemicals (eg, coffee contains 1000). Of
these, only 300 are nutrients, only some of which are essential.


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However, many nonnutrients in foods are
useful. For example, food additives (eg, preservatives, emulsifiers, antioxidants, stabilizers) improve the
production and stability of foods. Trace components (eg, spices, flavors, odors, colors, phytochemicals,
many other natural products) improve appearance and taste. Fiber:
 Fiber occurs in various forms (eg, cellulose, hemicellulose, pectin, gums). It 
increases GI motility,
prevents constipation, and helps control diverticular disease. Fiber is thought to accelerate the elimination
of cancer-causing substances produced by bacteria in the large intestine. Epidemiologic evidence
suggests an association between colon cancer and low fiber intake and a beneficial effect of fiber in
patients with functional bowel disorders, Crohn's disease, obesity, and hemorrhoids. Soluble fiber
(present in fruits, vegetables, oats, barley, and legumes) reduces the postprandial increase in blood
glucose and insulin and can reduce cholesterol levels. The typical Western diet is low in fiber (about 12 g/day) because of a high intake of highly refined wheat
flour and a low intake of fruits and vegetables.


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Increasing fiber intake to about 30 g/day by consuming
more vegetables, fruits, and high-fiber cereals and grains is generally recommended. However, very high
fiber intake may reduce absorption of certain minerals. Nutritional Requirements
Good nutrition aims to achieve and maintain a desirable body composition and high potential for physical
and mental work.


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Balancing energy intake with energy expenditure is necessary for a desirable body
weight. Energy expenditure depends on age, sex, weight (see 
Table 1-4
), and metabolic and physical
activity. If energy intake exceeds expenditure, weight is gained. Taking in about 100 calories/day more
than needed results in a weight gain of about 4 to 5 kg in a year. If energy intake is less than expenditure,
weight is lost.


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Daily dietary requirements for essential nutrients also depend on age, sex, weight, and metabolic and
physical activity. Every 5 yr, the Food and Nutrition Board of the National Academy of Sciences/National
Research Council and the US Department of Agriculture (USDA) issues the dietary reference intakes
(DRIs) for protein, energy, and some vitamins and minerals (see 
Tables 1-4
,
4-1
, and 
5-2
). For vitamins and minerals about which less is known, safe and adequate daily dietary
intakes are estimated.


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2608
) and infants (see p. 2703
) have special nutritional needs. The USDA publishes the Food Guide Pyramid, which specifies the number of recommended daily
servings of various food groups. The recommendations are individualized based on age, sex, and
physical activity (see
Table 1-5
). Generally, the recommended intake decreases with aging because physical activity tends to
decrease, resulting in less energy expended. The new Food Guide Pyramid emphasizes the following:
• Increasing consumption of whole grains
• Increasing consumption of vegetables and fruits
• Substituting fat-free or low-fat milk products (or equivalents) for whole-fat milk products
• Reducing consumption of saturated fats and trans fatty acids
• Exercising regularly
Adequate fluid intake is also important. Fats should constitute ≤ 30% of total calories, and saturated and trans fatty acids should constitute <
10%.


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Excess intake of saturated fats contributes to atherosclerosis. Substituting polyunsaturated fatty
acids for saturated fats can decrease the risk of atherosclerosis. Routine use of nutritional supplements is
not necessary or beneficial; some supplements can be harmful.


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For example, excess vitamin A can lead to
hypervitaminosis A, with headaches, osteoporosis, and rash. Nutrition in Clinical Medicine
Nutritional deficiencies can often worsen health outcomes (whether a disorder is present or not), and
some disorders (eg, malabsorption) can cause nutritional deficiencies. Also, many patients (eg, elderly
patients during acute hospitalization) have unsuspected nutritional deficiencies that require treatment. Many medical centers have multi-disciplinary nutrition support teams of physicians, nurses, dietitians, and
pharmacists to help the clinician prevent, diagnose, and treat occult nutritional deficiencies. Overnutrition may contribute to chronic disorders, such as cancer, hypertension, obesity, diabetes
mellitus, and coronary artery disease. Dietary restrictions are necessary in many hereditary metabolic
disorders (eg, galactosemia, phenylketonuria). Evaluation of Nutritional Status
Indications for nutritional evaluation include undesirable body weight or body composition, suspicion of
specific deficiencies or toxicities
[
Table 1-5. Recommended Dietary Intake for 40-yr-Olds with Moderate Physical Activity*]
of essential nutrients, and, in infants and children, insufficient growth or development. Nutritional status
should be evaluated routinely as part of the clinical examination for infants and children, the elderly,
people taking several drugs, people with psychiatric disorders, and people with systemic disorders that
last longer than several days. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1.


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Evaluating general nutritional status includes history, physical examination, and sometimes tests. If
undernutrition is suspected, laboratory tests (eg, albumin levels) and skin tests for delayed
hypersensitivity may be done (see p. 13
). Body composition analysis (eg, skinfold measurements, bioelectrical impedance analysis) is used to
estimate percentage of body fat and to evaluate obesity (see p. 58
).


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History includes questions about dietary intake, weight change, and risk factors for nutritional deficiencies
and a focused review of systems (see
Table 2-1
 on p. 11
). A dietitian can obtain a more detailed dietary history. It usually includes a list of foods
eaten within the previous 24 h and a food questionnaire. A food diary may be used to record all foods
eaten. The weighed ad libitum diet, in which the patient weighs and writes down all foods consumed, is
the most accurate record. A complete physical examination, including measurement of height and weight and distribution of body
fat, should be done. Body mass index (BMI)—weight(kg)/height(m)
2
, which adjusts weight for height (see
Table 6-2
 on p. 59
), is more accurate than height and weight tables.


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Distribution of body fat is important. Disproportionate truncal obesity (ie, waist/hip ratio > 0.8) is
associated with cardiovascular and cerebrovascular disorders, hypertension, and diabetes mellitus more
often than fat located elsewhere. Measuring waist circumference in patients with a BMI of < 35 helps
determine whether they have truncal obesity and helps predict risk of diabetes, hypertension,
hypercholesterolemia, and cardiovascular disorders. Risk is increased if waist circumference is > 102 cm
(> 40 in) in men or > 88 cm (> 35 in) in women. Nutrient-Drug Interactions
Nutrition can affect the body's response to drugs; conversely, drugs can affect the body's nutrition.


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Foods can enhance, delay, or decrease drug absorption. Foods impair absorption of many antibiotics. They can alter metabolism of drugs; eg, high-protein diets can accelerate metabolism of certain drugs by
stimulating 
cytochrome P-450. Eating grapefruit can inhibit cytochrome P-450 34A, slowing metabolism of
some drugs (eg, amiodarone, carbamazepine, cyclosporine, certain Ca channel blockers). Diets that alter
the bacterial flora may markedly affect the overall metabolism of certain drugs.


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Some foods affect the
body's response to drugs. For example, tyramine, a component of cheese and a potent vasoconstrictor,
can cause hypertensive crisis in some patients who take monoamine oxidase inhibitors and eat cheese. Nutritional deficiencies can affect drug absorption and metabolism. Severe energy and protein
deficiencies reduce enzyme tissue concentrations and may impair the response to drugs by reducing
absorption or protein binding and causing liver dysfunction. Changes in the GI tract can impair absorption
and affect the response to a drug. Deficiency of Ca, Mg, or zinc may impair drug metabolism. Vitamin C
deficiency decreases activity of drug-metabolizing enzymes, especially in the elderly. Many drugs affect appetite, food absorption, and tissue metabolism (see
Table 1-6
).


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Some drugs (eg, metoclopramide) increase GI motility, decreasing food absorption. Other
drugs (eg, opioids, anticholinergics) decrease GI motility. Some drugs are better tolerated if taken with
food.


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Certain drugs affect mineral metabolism. For example, diuretics, especially thiazides, and corticosteroids
can deplete body K, increasing susceptibility to digoxin-induced cardiac arrhythmias. Repeated use of
laxatives may deplete K. Cortisol, desoxycorticosterone, and aldosterone cause marked Na and water
retention, at least temporarily; retention is much less with prednisone, prednisolone, and some other
corticosteroid analogs. Sulfonylureas and lithium can impair the uptake or release of iodine by the thyroid.


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Oral contraceptives can lower blood zinc levels and increase copper levels. Certain antibiotics (eg,
tetracyclines) reduce iron absorption, as can certain foods (eg, vegetables, tea, bran).


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Certain drugs affect vitamin absorption or metabolism. Ethanol impairs thiamin utilization, and isoniazid
interferes with niacin and pyridoxine metabolism. Ethanol and oral contraceptives inhibit folate (folic acid)
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations
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absorption. Most patients receiving phenytoin, phenobarbital, primidone, or phenothiazines develop folate
deficiency, probably because hepatic microsomal drug-metabolizing enzymes are affected. Folate
supplements may
[
Table 1-6. Effects of Some Drugs on Nutrition]
make phenytoin less effective. Anticonvulsants can cause vitamin D deficiency. Malabsorption of vitamin
B
12
 can occur with use of aminosalicylic acid, slow-release K iodide, colchicine, trifluoperazine, ethanol,
and oral contraceptives. Oral contraceptives with a high progestin dose can cause depression, probably
because of metabolically induced tryptophan deficiency.


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Food Additives and Contaminants
Additives:
 Chemicals are often combined with foods to facilitate their processing and preservation or to
enhance their desirability.


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Only amounts of additives shown to be safe by laboratory tests are permitted in
commercially prepared foods. Weighing the benefits of additives (eg, reduced waste, increased variety of available foods, protection
against food-borne illness) against the risks is often complex. For example, nitrite, which is used in cured
meats, inhibits the growth of 
Clostridium botulinum
 and improves flavor. However, nitrite converts to
nitrosamines, which are carcinogens in animals. On the other hand, the amount of nitrite added to cured
meat is small compared with the amount from naturally occurring food nitrates converted to nitrite by the
salivary glands. Dietary vitamin C can reduce nitrite formation in the GI tract. Rarely, some additives (eg,
sulfites) cause food hypersensitivity (allergy) reactions.


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Most of these reactions are caused by ordinary
foods (see p. 1118
). Contaminants:
 Sometimes limited amounts of contaminants are allowed in foods because the
contaminants cannot be completely eliminated without damaging the foods. Common contaminants are
pesticides, heavy metals (lead, cadmium, mercury), nitrates (in green leafy vegetables), aflatoxins (in nuts
and milk), growth-promoting hormones (in dairy products and meat), animal hairs and feces, and insect
parts. FDA-estimated safe levels are levels that have not caused illness or adverse effects in people.


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However,
demonstrating a causal relationship between extremely low level exposures and adverse effects is
difficult; long-term adverse effects, although unlikely, are still possible. Safe levels are often determined
by consensus rather than by hard evidence.


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The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations
58


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Chapter 2. Undernutrition
Introduction
Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition—see 
Ch. 6
). Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired
metabolism, loss of nutrients due to diarrhea, or increased nutritional requirements (as occurs
in cancer or infection). Undernutrition progresses in stages; each stage usually takes
considerable time to develop. First, nutrient levels in blood and tissues change, followed by
intracellular changes in biochemical functions and structure. Ultimately, symptoms and signs
appear. Risk Factors
Undernutrition is associated with many disorders and circumstances, including poverty and social
deprivation. Risk is also greater at certain times (ie, during infancy, early childhood, adolescence,
pregnancy, breastfeeding, and old age).


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Infancy and childhood:
 Infants and children are particularly susceptible to undernutrition because of
their high demand for energy and essential nutrients. Because vitamin K does not readily cross the
placenta, neonates may be deficient, so all are given a single injection of vitamin K within 1 h of birth to
prevent hemorrhagic disease of the newborn, a life-threatening disorder (see pp. 46
 and
2783
).


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Infants fed only breast milk, which is typically low in vitamin D, are given supplemental vitamin D;
they can develop vitamin B
12
 deficiency if the mother is a vegan. Inadequately fed infants and children
are at risk of protein-energy undernutrition (PEU—previously called protein-energy malnutrition) and
deficiencies of iron, folate (folic acid), vitamins A and C, copper, and zinc. During adolescence, nutritional
requirements increase because the growth rate accelerates.


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Pregnancy and breastfeeding:
 Requirements for nutrients increase during pregnancy and
breastfeeding. Aberrations of diet, including pica (consumption of nonnutritive substances, such as clay
and charcoal), may occur during 
pregnancy. Anemia due to iron deficiency is common, as is anemia due
to folate deficiency, especially among women who have taken oral contraceptives.


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Vitamin D deficiency is
common during late pregnancy, predisposing the child to decreased bone mass. Old age:
 Aging—even when disease or dietary deficiency is absent—leads to sarcopenia (progressive
loss of lean body mass), starting after age 40 and eventually amounting to a muscle loss of about 10 kg
(22 lb) in men and 5 kg (11 lb) in women. Undernutrition contributes to sarcopenia, and sarcopenia
accounts for many of the complications of undernutrition (eg, decreased nitrogen balance, increased
susceptibility to infections). Causes of sarcopenia include the following:
• Decreased physical activity
• Decreased food intake
• Increased levels of cytokines (particularly interleukin-6)
• Decreased levels of growth hormone and mechano growth factor (insulin-like growth factor-3)
• In men, decreasing androgen levels
Aging decreases basal metabolic rate (due mainly to decreased fat-free mass), total body weight, height,
and skeletal mass; aging increases mean body fat (as a percentage of body weight) to about 30% (from
20%) in men and to 40% (from 27%) in women. From age 20 to 80, food intake decreases, especially in men.


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Anorexia due to aging itself has many
causes, including reduced adaptive relaxation of the stomach's fundus, increased release and activity of
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition
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cholecystokinin (which produces satiation), and increased leptin (an anorectic hormone produced by fat
cells). Diminished taste and smell can decrease eating pleasure but usually decrease food intake only
slightly. Anorexia may have other causes (eg, loneliness, inability to shop or prepare meals, dementia,
some chronic disorders, use of certain drugs).


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Depression is a common cause. Occasionally, anorexia
nervosa (sometimes called anorexia tardive in the elderly), paranoia, or mania interferes with eating. Dental problems limit the ability to chew and subsequently to digest foods. Swallowing difficulties (eg, due
to strokes, other neurologic disorders, esophageal candidiasis, or xerostomia) are common. Poverty or
functional impairment limits access to nutrients. The institutionalized elderly are at particular risk of PEU. They are often confused and may be unable to
express hunger or preferences for foods.


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Chewing or
swallowing may be very slow, making it tedious for another person to feed them enough food. In the elderly, particularly the institutionalized elderly, inadequate intake and often decreased absorption
or synthesis of vitamin D, increased demand for vitamin D, and inadequate exposure to sunshine
contribute to osteomalacia (see p. 41
).


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Disorders and medical procedures:
 Diabetes, some chronic disorders that affect the GI tract, intestinal
resection, and certain other GI surgical procedures tend to impair absorption of fat-soluble vitamins,
vitamin B
12
, Ca, and iron. Gluten enteropathy, pancreatic insufficiency, or other disorders can result in
malabsorption. Decreased absorption possibly contributes to iron deficiency and osteoporosis. Liver
disorders impair storage of vitamins A and B
12
 and interfere with metabolism of protein and energy
sources. Renal insufficiency predisposes to protein, iron, and vitamin D deficiencies. Anorexia causes
some patients with cancer or depression and many with AIDS to consume inadequate amounts of food. Infections, trauma, hyperthyroidism, extensive burns, and prolonged fever increase metabolic demands. Any condition that increases cytokines may be accompanied by muscle loss, lipolysis, low albumin levels,
and anorexia. Vegetarian diets:
 Iron deficiency can occur in ovo-lacto vegetarians (although such a diet can be
compatible with good health). Vegans may develop vitamin B
12
 deficiency unless they consume yeast
extracts or Asian-style fermented foods. Their intake of Ca, iron, and zinc also tends to be low.


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A fruit-only
diet is not recommended because it is deficient in protein, Na, and many micronutrients. Fad diets:
 Some fad diets result in vitamin, mineral, and protein deficiencies; cardiac, renal, and
metabolic disorders; and sometimes death. Very low calorie diets (< 400 kcal/day) cannot sustain health
for long. Drugs and nutritional supplements:
 Many drugs (eg, appetite suppressants, digoxin) decrease
appetite; others impair nutrient absorption or metabolism. Some drugs (eg, stimulants) have catabolic
effects. Certain drugs can impair absorption of many nutrients; eg, anticonvulsants can impair absorption
of vitamins. Alcohol or drug dependency:
 Patients with alcohol or drug dependency may neglect their nutritional
needs. Absorption and metabolism of nutrients may also be impaired. IV drug addicts typically become
undernourished, as do
[
Table 2-1. Symptoms and Signs of Nutritional Deficiency]
alcoholics who consume ≥ 1 quart of hard liquor/day. Alcoholism can cause deficiencies of Mg, zinc, and
certain vitamins, including thiamin. Symptoms and Signs
Symptoms vary depending on the cause and type of undernutrition (see p.


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Diagnosis is based on results of medical and diet histories, physical examination, body composition
analysis (see p. 58
), and selected laboratory tests.


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History:
 History should include questions about dietary intake (see
Fig. 2-1
), recent changes in weight, and risk factors for undernutrition, including drug and alcohol use. Unintentional loss of ≥ 10% of usual body weight during a 3-mo period indicates a high probability of
undernutrition. Social history should include questions about whether money is available for food and
whether the patient can shop and cook. Review of systems should focus on symptoms of nutritional deficiencies (see 
Table 2-1
). For example,
impaired night vision may indicate vitamin A deficiency. Physical examination:
 Physical examination should include measurement of height and weight,
inspection of body fat distribution, and anthropometric measurements of lean body mass.


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Body mass
index (BMI = weight(kg)/height(m)
2
) adjusts weight for height (see
Table 6-2
 on p. 59
). If weight is < 80% of what is predicted for the patient's height or if BMI is ≤ 18,
undernutrition should be suspected. Although these findings are useful in diagnosing undernutrition and
are acceptably sensitive, they lack specificity.


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2-1. Mini nutritional assessment.]
The mid upper arm muscle area estimates lean body mass. This area is derived from the triceps skinfold
thickness (TSF) and mid upper arm circumference. Both are measured at the same site, with the patient's
right arm in a relaxed position. The average mid upper arm circumference is about 32 ± 5 cm for men and
28 ± 6 cm for women. The formula for calculating the mid upper arm muscle area in cm
2
 is as follows:
This formula corrects the upper arm area for fat and bone. Average values for the mid upper arm muscle
area are 54 ± 11 cm
2
 for men and 30 ± 7 cm
2
 for women. A value < 75% of this standard (depending on
age) indicates depletion of lean body mass (see
Table 2-2
).


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This measurement may be affected by physical activity, genetic factors, and age-related
muscle loss.


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Physical examination should focus on signs of specific nutritional deficiencies. Signs of PEU (eg, edema,
muscle wasting, skin changes) should be sought. Examination should also focus on signs of conditions
that could predispose to nutritional deficiencies, such as dental problems. Mental status should be
assessed, because depression and cognitive impairment can lead to weight loss. The widely used Subjective Global Assessment (SGA) uses information from the patient history (eg,
weight loss, change in intake, GI symptoms), physical examination findings (eg, loss of muscle and
subcutaneous fat, edema, ascites), and the clinician's judgment of the patient's nutritional status. The
Mini Nutritional Assessment (MNA) has been validated and is widely used, especially for elderly patients
(see 
Fig. 2-1
). The Simplified Nutrition Assessment Questionnaire (SNAQ), a simple, validated method of
predicting future weight loss, may be used (see
Fig. 2-2
).


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Testing:
 The extent of laboratory testing needed is unclear and may depend on the patient's
circumstances. If the cause is obvious and correctable (eg, a wilderness survival situation), testing is
probably of little benefit.


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Other patients may require more detailed evaluation. Serum albumin measurement is the laboratory test most often used. Decreases in albumin and other
proteins (eg, prealbumin [transthyretin], transferrin, retinol-binding protein) may indicate protein deficiency
or PEU. As undernutrition progresses, albumin decreases slowly; prealbumin, transferrin, and retinol-
binding protein decrease rapidly. Albumin measurement is inexpensive and predicts morbidity and
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mortality better than measurement of the other proteins. However, the correlation of albumin with
morbidity and mortality may be related to nonnutritional as well as nutritional factors. Inflammation
produces cytokines that cause albumin and other nutritional protein markers to extravasate, decreasing
serum levels. Because prealbumin, transferrin, and retinol-binding protein decrease more rapidly during
starvation than does albumin, their measurements are sometimes used to diagnose or assess the severity
of acute starvation. However, whether they are more sensitive or specific than albumin is unclear. Total lymphocyte count, which often decreases as undernutrition progresses, may be determined. Undernutrition causes a marked decline in CD4+ T lymphocytes, so this count may not be useful in
patients who have AIDS. Skin tests using antigens can detect impaired cell-mediated immunity in PEU and in some other disorders
of undernutrition (see p. 1098
).


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Other laboratory tests, such as measuring vitamin and mineral levels, are used selectively to diagnose
specific deficiencies.


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Mid Upper Arm Muscle Area in Adults]
[
Figure 2-2. Simplified Nutrition Assessment Questionnaire (SNAQ).]
Protein-Energy Undernutrition
Protein-energy undernutrition (PEU), previously called protein-energy malnutrition, is an energy
deficit due to chronic deficiency of all macronutrients. It commonly includes deficiencies of
many micronutrients.


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PEU can be sudden and total (starvation) or gradual. Severity ranges from
subclinical deficiencies to obvious wasting (with edema, hair loss, and skin atrophy) to
starvation.


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Diagnosis usually involves laboratory
testing, including serum albumin. Treatment consists of correcting fluid and electrolyte deficits
with IV solutions, then gradually replenishing nutrients, orally if possible. In developed countries, PEU is common among the institutionalized elderly (although often not suspected)
and among patients with disorders that decrease appetite or impair nutrient digestion, absorption, or
metabolism. In developing countries, PEU affects children who do not consume enough calories or
protein. Classification and Etiology
PEU is graded as mild, moderate, or severe. Grade is determined by calculating weight as a percentage
of expected weight for length or height using international standards (normal, 90 to 110%; mild PEU, 85 to
90%; moderate, 75 to 85%; severe, <75%). PEU may be primary or secondary.


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Primary PEU is caused by inadequate nutrient intake. Secondary PEU
results from disorders or drugs that interfere with nutrient use. Primary PEU:
 Worldwide, primary PEU occurs mostly in children and the elderly who lack access to
nutrients, although a common cause in the elderly is depression. PEU can also result from fasting or
anorexia nervosa. Child or elder abuse may be a cause. In children, chronic primary PEU has 2 common forms: marasmus and kwashiorkor. The form depends on
the balance of nonprotein and protein sources of energy. Starvation is an acute severe form of primary
PEU. Marasmus (also called the dry form of PEU) causes weight loss and depletion of fat and muscle. In
developing countries, marasmus is the most common form of PEU in children. Kwashiorkor (also called the wet, swollen, or edematous form) is associated with premature abandonment
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition
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of breastfeeding, which typically occurs when a younger sibling is born, displacing the older child from the
breast. So children with kwashiorkor tend to be older than those with marasmus. Kwashiorkor may also
result from an acute illness, often gastroenteritis or another infection (probably secondary to cytokine
release), in a child who already has PEU. A diet that is more deficient in protein than energy may be more
likely to cause kwashiorkor than marasmus. Less common than marasmus, kwashiorkor tends to be
confined to specific parts of the world, such as rural Africa, the Caribbean, and the Pacific islands. In
these areas, staple foods (eg, yams, cassavas, sweet potatoes, green bananas) are low in protein and
high in carbohydrates. In kwashiorkor, cell membranes leak, causing extravasation of intravascular fluid
and protein, resulting in peripheral edema. Starvation is a complete lack of nutrients.


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It occasionally occurs when food is available (as in fasting or
anorexia nervosa) but usually occurs because food is unavailable (eg, during famine or wilderness
exposure). Secondary PEU:
 This type most commonly results from the following:
• Disorders that affect GI function: These disorders can interfere with digestion (eg, pancreatic
insufficiency), absorption (eg, enteritis, enteropathy), or lymphatic transport of nutrients (eg,
retroperitoneal fibrosis, Milroy's disease). • Wasting disorders: In wasting disorders (eg, AIDS, cancer) and renal failure, catabolism causes cytokine
excess, resulting in undernutrition via anorexia and cachexia (wasting of muscle and fat). End-stage
heart failure can cause cardiac cachexia, a severe form of undernutrition; mortality rate is particularly
high. Factors contributing to cardiac cachexia may include passive hepatic congestion (causing
anorexia), edema of the intestinal tract (impairing absorption), and, in advanced disease, increased O
2
requirement due to anaerobic metabolism. Wasting disorders can decrease appetite or impair
metabolism of nutrients.


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• Conditions that increase metabolic demands: These conditions include infections, hyperthyroidism,
pheochromocytoma, other endocrine disorders, burns, trauma, surgery, and other critical illnesses. Pathophysiology
The initial metabolic response is decreased metabolic rate.


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To supply energy, the body first breaks down
adipose tissue. However, later when these tissues are depleted, the body may use protein for energy,
resulting in a negative nitrogen balance. Visceral organs and muscle are broken down and decrease in
weight.


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Loss of organ weight is greatest in the liver and intestine, intermediate in the heart and kidneys,
and least in the nervous system. Symptoms and Signs
Symptoms of moderate PEU can be constitutional or involve specific organ systems. Apathy and irritability
are common.


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Cognition and sometimes
consciousness are impaired. Temporary lactose deficiency and achlorhydria develop. Diarrhea is common
and can be aggravated by deficiency of intestinal disaccharidases, especially lactase (see p. 157
).


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Gonadal tissues atrophy. PEU can cause amenorrhea in women and loss of libido in men and women. Wasting of fat and muscle is common in all forms of PEU. In adult volunteers who fasted for 30 to 40
days, weight loss was marked (25% of initial weight). If starvation is more prolonged, weight loss may
reach 50% in adults and possibly more in children. In adults, cachexia is most obvious in areas where prominent fat depots normally exist. Muscles shrink
and bones protrude. The skin becomes thin, dry, inelastic, pale, and cold. The hair is dry and falls out
easily, becoming sparse. Wound healing is impaired.


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In elderly patients, risk of hip fractures and pressure
(decubitus) ulcers increases. With acute or chronic severe PEU, heart size and cardiac output decrease; pulse slows
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition
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[
Table 2-3. Values Commonly Used to Grade the Severity of Protein-Energy Undernutrition]
and BP falls. Respiratory rate and vital capacity decrease.


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Body temperature falls, sometimes contributing
to death. Edema, anemia, jaundice, and petechiae can develop. Liver, kidney, or heart failure may occur. Cell-mediated immunity is impaired, increasing susceptibility to infections. Bacterial infections (eg,
pneumonia, gastroenteritis, otitis media, UTIs, sepsis) are common in both forms of PEU. Infections result
in release of cytokines, which cause anorexia, worsen muscle wasting, and cause a marked decrease in
serum albumin levels. Marasmus in infants causes hunger, weight loss, growth retardation, and wasting of subcutaneous fat
and muscle. Ribs and facial bones appear prominent.


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Loose, thin skin hangs in folds. Kwashiorkor is characterized by peripheral and periorbital edema. The abdomen protrudes because
abdominal muscles are weakened, the intestine is distended, the liver enlarges, and ascites is present. The skin is dry, thin, and wrinkled; it can become hyperpigmented and fissured and later hypopigmented,
friable, and atrophic.


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Skin in different areas of the body may be affected at different times. The hair can
become thin, reddish brown, or gray. Scalp hair falls out easily, eventually becoming sparse, but eyelash
hair may grow excessively. Alternating episodes of undernutrition and adequate nutrition may cause the
hair to have a dramatic "striped flag" appearance. Affected children may be apathetic but become irritable
when held.


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Total starvation is fatal in 8 to 12 wk. Thus, certain symptoms of PEU do not have time to develop. Diagnosis
• Diagnosis usually based on history
• To determine severity: BMI, serum albumin, total lymphocyte count, CD4+ count, serum transferrin
• To diagnose complications and consequences: CBC, electrolytes, BUN, glucose, Ca, Mg, phosphate
Diagnosis can be based on history when dietary intake is markedly inadequate. The cause of inadequate
intake, particularly in children, needs to be identified.


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In children and adolescents, child abuse and
anorexia nervosa should be considered. Physical examination findings can usually confirm the diagnosis.


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Laboratory tests are required if dietary
history does not clearly indicate inadequate caloric intake. Measurement of serum albumin, total
lymphocyte count, CD4+ T lymphocytes, transferrin, and response to skin antigens may help determine
the severity of PEU (see 
Table 2-3
) or confirm the diagnosis in borderline cases. Many other test results
may be abnormal: eg, decreased levels of hormones, vitamins, lipids, cholesterol, prealbumin, insulin
growth factor-1, fibronectin, and retinol-binding protein. Urinary creatine and methylhistidine levels can be
used to gauge the degree of muscle wasting. Because protein catabolism slows, urinary urea level also
decreases.


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These findings rarely affect treatment. Laboratory tests are required to identify causes of suspected secondary PEU. C-reactive protein or
soluble interleukin-2 receptor should be measured when the cause of undernutrition 
is unclear; these
measurements can help determine whether there is cytokine excess. Thyroid function tests may also be
done.


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Other laboratory tests can detect associated abnormalities that may require treatment. Serum
electrolytes, BUN, glucose, and possibly levels of Ca, Mg, and phosphate should be measured. Levels of
serum glucose, electrolytes (especially K, occasionally Na), phosphate, Ca, and Mg are usually low. BUN
is often low unless renal failure is present. Metabolic acidosis may be present. CBC is usually obtained;
normocytic anemia (usually due to protein deficiency) or microcytic anemia (due to simultaneous iron
deficiency) is usually present. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2.


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Stool cultures should be obtained and checked for ova and parasites if diarrhea is severe or does not
resolve with treatment. Sometimes urinalysis, urine culture, blood cultures, tuberculin testing, and a chest
x-ray are used to diagnose occult infections because people with PEU may have a muted response to
infections. Prognosis
Children:
 In children, mortality varies from 5 to 40%.


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Mortality rates are lower in children with mild PEU
and those given intensive care. Death in the first days of treatment is usually due to electrolyte deficits,
sepsis, hypothermia, or heart failure. Impaired consciousness, jaundice, petechiae, hyponatremia, and
persistent diarrhea are ominous signs.


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Resolution of apathy, edema, and anorexia is a favorable sign. Recovery is more rapid in kwashiorkor than in marasmus. Long-term effects of PEU in children are not fully documented. Some children develop chronic
malabsorption and pancreatic insufficiency. In very young children, mild intellectual disability may develop
and persist until at least school age. Permanent cognitive impairment may occur, depending on the
duration, severity, and age at onset of PEU. Adults:
 In adults, PEU can result in morbidity and mortality (eg, progressive weight loss increases
mortality rate for elderly patients in nursing homes). In elderly patients, PEU increases the risk of
morbidity and mortality due to surgery, infections, or other disorders.


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Except when organ failure occurs,
treatment is uniformly successful. Treatment
• Usually, oral feeding
• Possibly avoidance of lactose (eg, if persistent diarrhea suggests lactose intolerance)
• Supportive care (eg, environmental changes, assistance with feeding, orexigenic drugs)
• For children, feeding delayed 24 to 48 h
Worldwide, the most important preventive strategy is to reduce poverty and improve nutritional education
and public health measures. Mild or moderate PEU, including brief starvation, can be treated by providing a balanced diet, preferably
orally. Liquid oral food supplements (usually lactose-free) can be used when solid food cannot be
adequately ingested.


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Diarrhea often complicates oral feeding because starvation makes the GI tract more
likely to move bacteria into Peyer's patches, facilitating infectious diarrhea. If diarrhea persists
(suggesting lactose intolerance), yogurt-based rather than milk-based formulas are given because people
with lactose intolerance can tolerate yogurt. Patients should also be given a multivitamin supplement.


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Severe PEU or prolonged starvation requires treatment in a hospital with a controlled diet. The first
priority is to correct fluid and electrolyte abnormalities (see 
Ch.


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97
) and treat infections. Next is to supply
macronutrients orally or, if necessary (eg, when swallowing is difficult), through a feeding tube, a
nasogastric tube (usually), or a gastrostomy tube. Parenteral nutrition is indicated if malabsorption is
severe (see p. 23
).


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Other treatments may be needed to correct specific deficiencies, which may become evident as weight
increases. To avoid deficiencies, patients should take micronutrients at about twice the recommended
daily allowance (RDA) until recovery is complete. Children:
 Underlying disorders should be treated. For children with diarrhea, feeding may be delayed 24
to 48 h to avoid making the diarrhea worse; during this interval, children require oral or IV rehydration. Feedings are given often (6 to 12 times/day) but, to avoid overwhelming the limited intestinal absorptive
capacity, are limited to small amounts (< 100 mL). During the first week, milk-based formulas with
supplements added are usually given in progressively increasing amounts; after a week, the full amounts
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of 175 kcal/kg and 4 g of protein/kg can be given. Twice the RDA of micronutrients should be given,
using commercial multivitamin supplements. After 4 wk, the formula can be replaced with whole milk plus
cod liver oil and solid foods, including eggs, fruit, meats, and yeast. Energy distribution among macronutrients should be about 16% protein, 50% fat, and 34% carbohydrate. An example is a combination of powdered cow's skimmed milk (110 g), sucrose (100 g), vegetable oil (70
g), and water (900 mL). Many other formulas (eg, whole [full-fat] fresh milk plus corn oil and maltodextrin)
can be used. Milk powders used in formulas are diluted with water. Usually, supplements should be added to formulas:
• Mg 0.4 mEq/kg/day IM is given for 7 days. • B-complex vitamins at twice the RDA are given parenterally for the first 3 days, usually with vitamin A,
phosphorus, zinc, manganese, copper, iodine, fluoride, molybdenum, and selenium. • Because absorption of oral iron is poor in children with PEU, oral or IM iron supplementation may be
necessary. Parents are taught about nutritional requirements.


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Adults:
 Underlying disorders should be treated. For example, if AIDS or cancer results in excess cytokine
production, megestrol acetate or medroxyprogesterone may improve food intake. However, because
these drugs dramatically decrease testosterone in men (possibly causing muscle loss), testosterone
should be replaced. Because these drugs can cause adrenal insufficiency, they should be used only
short-term (< 3 mo).


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In patients with functional limitations, home delivery of meals and feeding assistance are key. An orexigenic drug, such as the cannabis extract dronabinol, should be given to patients with anorexia
when no cause is obvious or to patients at the end of life when anorexia impairs quality of life. An
anabolic steroid (eg, enanthate, nandrolone, testosterone) or growth hormone can benefit patients with
cachexia due to renal failure and possibly elderly patients (eg, by increasing lean body mass or possibly
by improving function). Correction of PEU in adults generally resembles that in children; feedings are often limited to small
amounts.


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A commercial formula for oral
feeding can be used. Daily nutrient supply should be given at a rate of 60 kcal/kg and 1.2 to 2 g of
protein/kg. If liquid oral supplements are used with solid food, they should be given at least 1 h before
meals so that the amount of food eaten at the meal is not reduced. Treatment of institutionalized elderly patients with PEU requires multiple interventions:
• Environmental measures (eg, making the dining area more attractive)
• Feeding assistance
• Changes in diet (eg, use of food enhancers and caloric supplements between meals)
• Treatment of depression and other underlying disorders
• Use of orexigenics, anabolic steroids, or both
The long-term use of gastrostomy tube feeding is essential for patients with severe dysphagia; its use in
patients with dementia is controversial. Increasing evidence supports the avoidance of unpalatable
therapeutic diets (eg, low salt, diabetic, low cholesterol) in institutionalized patients because these diets
decrease food intake and may cause severe PEU. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2.


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Complications of treatment:
 Treatment of PEU can cause complications (refeeding syndrome),
including fluid overload, electrolyte deficits, hyperglycemia, cardiac arrhythmias, and diarrhea. Diarrhea is
usually mild and resolves; however, diarrhea in patients with severe PEU occasionally causes severe
dehydration or death. Causes of diarrhea (eg, sorbitol used in elixir tube feedings, 
Clostridium difficile
 if
the patient has received an antibiotic) may be correctable. Osmotic diarrhea due to excess calories is rare
in adults and should be considered only when other causes have been excluded. Because PEU can impair cardiac and renal function, hydration can cause intravascular volume overload. Treatment decreases extra-cellular K and Mg.


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Depletion of K or Mg may cause arrhythmias. Carbohydrate metabolism that occurs during treatment stimulates insulin release, which drives phosphate
into cells. Hypophosphatemia can cause muscle weakness, paresthesias, seizures, coma, and
arrhythmias. Because phosphate levels can change rapidly during parenteral feeding, levels should be
measured regularly. During treatment, endogenous insulin may become ineffective, leading to hyperglycemia.


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Fatal ventricular arrhythmias can develop, possibly caused by a
prolonged QT interval. Carnitine Deficiency
Carnitine deficiency results from inadequate intake of or inability to metabolize the amino acid
carnitine. It can cause a heterogeneous group of disorders.


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Muscle metabolism is impaired,
causing myopathy, hypoglycemia, or cardiomyopathy. Infants typically present with
hypoglycemic, hypoketotic encephalopathy. Most often, treatment consists of dietary L-
carnitine. The amino acid carnitine is required for the transport of long-chain fatty acyl coenzyme A (CoA) esters
into myocyte mitochondria, where they are oxidized for energy. Carnitine is obtained from foods,
particularly animal-based foods, and via endogenous synthesis. Causes of carnitine deficiency include the following:
• Inadequate intake (eg, due to fad diets, lack of access, or long-term TPN)
• Inability to metabolize carnitine due to enzyme deficiencies (eg, carnitine palmitoyltransferase deficiency,
methylmalonicaciduria, propionicacidemia, isovalericacidemia)
• Decreased endogenous synthesis of carnitine due to a severe liver disorder
• Excess loss of carnitine due to diarrhea, diuresis, or hemodialysis
• A hereditary disorder in which carnitine leaks from renal tubules
• Increased requirements for carnitine when ketosis is present or demand for fat oxidation is high (eg,
during a critical illness such as sepsis or major burns; after major surgery of the GI tract)
• Decreased muscle carnitine levels due to mitochondrial impairment (eg, due to use of zidovudine)
• Use of valproate
The deficiency may be generalized (systemic) or may affect mainly muscle (myopathic). Symptoms and Signs
Symptoms and the age at which symptoms appear depend on the cause. Carnitine deficiency may cause
muscle necrosis, myoglobinuria, lipid-storage myopathy, hypoglycemia, fatty liver, and hyperammonemia
with muscle aches, fatigue, confusion, and cardiomyopathy. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2.


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Diagnosis
In neonates, carnitine palmitoyltransferase deficiency is diagnosed using mass spectrometry to screen
blood. Prenatal diagnosis may be possible using amniotic villous cells. In adults, the definitive diagnosis is
based on acylcarnitine levels in serum, urine, and tissues (muscle and liver for systemic deficiency;
muscle only for myopathic deficiency). Treatment
• Avoidance of fasting and strenuous exercise
• Dietary interventions, based on cause
Carnitine deficiency due to inadequate dietary intake, increased requirements, excess losses, decreased
synthesis, or (sometimes) enzyme deficiencies can be treated by giving L-carnitine 25 mg/kg po q 6 h. All patients must avoid fasting and strenuous exercise.


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Consuming uncooked cornstarch at bedtime
prevents early morning hypoglycemia. Some patients require supplementation with medium-chain
triglycerides and essential fatty acids (eg, linoleic acid, linolenic acid).


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Patients with a fatty acid oxidation
disorder require a high-carbohydrate, low-fat diet. Essential Fatty Acid Deficiency
Essential fatty acid (EFA) deficiency is rare, occurring most often in infants fed diets deficient in
EFAs. Signs include scaly dermatitis, alopecia, thrombocytopenia, and, in children, growth
retardation.


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Dietary replenishment of EFAs reverses the deficiency. The EFAs linoleic and linolenic acid are substrates for the endogenous synthesis of other fatty acids that
are needed for many physiologic processes, including maintaining the integrity of skin and cell
membranes and synthesizing prostaglandins and leukotrienes. For example, eicosapentaenoic acid and
docosahexaenoic acid, synthesized from EFAs, are important components of the brain and retina. For EFA deficiency to develop, dietary intake must be very low.


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Even small amounts of EFAs can prevent
EFA deficiency. Cow's milk has only about 25% of the linoleic acid in human milk, but when ingested in
normal amounts, it has enough linoleic acid to prevent EFA deficiency. Total fat intake of people in many
developing countries may be very low, but the fat is often vegetable based, with large amounts of linoleic
acid and enough linolenic acid to prevent EFA deficiency. Babies fed a formula low in linoleic acid, such as a skim-milk formula, can develop EFA deficiency. EFA
deficiency used to result from long-term TPN if fat was not included. But now, most TPN solutions include
fat emulsions to prevent EFA deficiency. In patients with fat malabsorption or increased metabolic needs
(eg, because of surgery, multiple trauma, or burns), laboratory evidence of EFA deficiency may be
present without clinical signs. Dermatitis due to EFA deficiency is generalized and scaly; in infants, it can resemble congenital
ichthyosis. The dermatitis increases water loss from the skin. Diagnosis is usually clinical; however, laboratory assays are now available in large research centers. Treatment consists of dietary EFAs, reversing the deficiency. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2.


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Chapter 3. Nutritional Support
Introduction
Many undernourished patients need nutritional support, which aims to increase lean body mass. Oral
feeding can be difficult for some patients with anorexia or with eating or absorption problems. Behavioral
measures that sometimes enhance oral intake include the following:
• Encouraging patients to eat
• Heating or seasoning foods
• Providing favorite or strongly flavored foods
• Encouraging patients to eat small portions
• Scheduling around meals
• Assisting patients with feeding
If behavioral measures are ineffective, nutritional support—oral, enteral tube, or parenteral nutrition—is
indicated, except sometimes for dying or severely demented patients (see p. 25
).


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Predicting Nutritional Requirements
Nutritional requirements are predicted so that interventions can be planned. Requirements can be
estimated by formulas or measured by indirect calorimetry. Indirect calorimetry requires use of a metabolic
cart (a closed rebreathing system that determines energy expenditure based on total CO
2
 production),
which requires special expertise and is not always available. Thus, total energy expenditure (TEE) and
protein requirements usually are estimated. Energy expenditure:
 TEE varies based on the patient's weight, activity level, and degree of metabolic
stress (metabolic demands); TEE ranges from 25 kcal/kg/day for people who are sedentary and not under
stress to about 40 kcal/kg/day for people who are critically ill. TEE equals the sum of
• Resting metabolic rate (RMR, or resting energy expenditure rate), which is normally about 70% of TEE
• Energy dissipated by metabolism of food (10% of TEE)
• Energy expended during physical activity (20% of TEE)
Undernutrition can decrease RMR up to 20%. Conditions that increase metabolic stress (eg, critical
illness, infection, inflammation, trauma, surgery) can increase RMR but rarely by > 50%.


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The Mifflin-St. Jeor equation estimates RMR more precisely and with fewer errors than the commonly
used Harris-Benedict equation, usually providing results that are within 20% of those measured by
indirect calorimetry. The Mifflin-St. Jeor equation estimates RMR as follows:
Men
: kcal / day = 66 + (13.7 × wt[kg]) + (5 × height[cm]) - (6.8 × age)
Women
: kcal / day = 665 + (9.6 × wt[kg]) + (1.8 × height[cm]) - (4.7 × age)
TEE can be estimated by adding about 10% (for sedentary people) to about 40% (for people who are
critically ill) to RMR. Protein requirements:
 For healthy people, protein requirements are estimated at 0.8 g/kg/day.


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However, for patients with metabolic stress or kidney failure and for elderly patients, requirements may be
higher (see
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3.


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Table 3-1
). Assessing Response to Nutritional Support
There is no gold standard to assess response. Clinicians commonly use indicators of lean body mass
such as the following:
• Body mass index (BMI)
• Body composition analysis
• Body fat distribution (see pp. 11
 and 
58
)
Nitrogen balance, response to skin antigens, muscle strength measurement, and indirect calorimetry can
also be used.


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[
Table 3-1. Estimated Adult Daily Protein Requirement]
Nitrogen balance,
 which reflects the balance between protein needs and supplies, is the difference
between amount of nitrogen ingested and amount lost. A positive balance (ie, more ingested than lost)
implies adequate intake. Precise measurement is impractical, but estimates help assess response to
nutritional support. Nitrogen intake is estimated from protein intake: nitrogen (g) equals protein (g)/6.25. Estimated nitrogen losses consist of urinary nitrogen losses (estimated by measuring urea nitrogen
content of an accurately obtained 24-h urine collection) plus stool losses (estimated at 1 g/day if stool is
produced; negligible if stool is not produced) plus insensible and other unmeasured losses (estimated at
3 g). Response to skin antigens
, a measure of delayed hypersensitivity, often increases to normal as
undernourished patients respond to nutritional support.


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However, other factors can affect response to
skin antigens. Muscle strength
 indirectly reflects increases in lean body mass.


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It can be measured quantitatively, by
hand-grip dynamometry, or electrophysiologically (typically by stimulating the ulnar nerve with an
electrode). Levels of acute-phase reactant
 serum proteins (particularly short-lived proteins such as prealbumin
[transthyretin], retinol-binding protein, and transferrin) sometimes correlate with improved nutritional
status, but these levels correlate better with inflammatory conditions. Enteral Tube Nutrition
Enteral tube nutrition is indicated for patients who have a functioning GI tract but cannot ingest enough
nutrients orally because they are unable or unwilling to take oral feedings.


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Compared with parenteral
nutrition, enteral nutrition has the following advantages:
• Better preservation of the structure and function of the GI tract
• Lower cost
• Probably fewer complications, particularly infections
Specific indications
 for enteral nutrition include the following:
• Prolonged anorexia
• Severe protein-energy undernutrition
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support
70


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• Coma or depressed sensorium
• Liver failure
• Inability to take oral feedings due to head or neck trauma or neurologic disorders
• Critical illnesses (eg, burns) causing metabolic stress
Other indications may include bowel preparation for surgery in seriously ill or undernourished patients,
closure of enterocutaneous fistulas, and small-bowel adaptation after massive intestinal resection or in
disorders that may cause malabsorption (eg, Crohn's disease). Procedure:
 If tube feeding is needed for ≤ 4 to 6 wk, a small-caliber, soft nasogastric or nasoenteric (eg,
nasoduodenal) tube made of silicone or polyurethane is usually used.


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If a nasal injury or deformity makes
nasal placement difficult, an orogastric or other oroenteric tube can be placed. Tube feeding for > 4 to 6 wk usually requires a gastrostomy or jejunostomy tube, placed endoscopically,
surgically, or radiologically. Choice depends on physician capabilities and patient preference. Jejunostomy tubes are useful for patients with contraindications to gastrostomy (eg, gastrectomy, bowel
obstruction proximal to the jejunum). However, these tubes do not pose less risk of tracheobronchial
aspiration than gastrostomy tubes, as is often thought. Jejunostomy tubes are easily dislodged and are
usually used only for inpatients. Feeding tubes are surgically placed if endoscopic and radiologic placement is unavailable, technically
impossible, or unsafe (eg, because of overlying bowel).


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Open or laparoscopic techniques can be used. Formulas:
 Liquid formulas commonly used include feeding modules and polymeric or other specialized
formulas.


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Feeding modules
 are commercially available products that contain a single nutrient, such as proteins,
fats, or carbohydrates. Feeding modules may be used individually to treat a specific deficiency or
combined with other formulas to completely satisfy nutritional requirements. Polymeric formulas
 (including blenderized food and milk-based or lactose-free commercial formulas)
are commercially available and generally provide a complete, balanced diet. For oral or tube feedings,
they are usually preferred to feeding modules. In hospitalized patients, lactose-free formulas are the most
commonly used polymeric formulas. However, milk-based formulas tend to taste better than lactose-free
formulas. Patients with lactose intolerance may be able to tolerate milk-based formulas given slowly by
continuous infusion. Specialized formulas
 include hydrolyzed protein or sometimes amino acid formulas, which are used for
patients who have difficulty digesting complex proteins.


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However, these formulas are expensive and
usually unnecessary. Most patients with pancreatic insufficiency, if 
given enzymes, and most patients with
malabsorption can digest complex proteins. Other specialized formulas (eg, calorie- and protein-dense
formulas for patients whose fluids are restricted, fiber-enriched formulas for constipated patients) may be
helpful. Administration:
 Patients should be sitting upright at 30 to 45° during tube feeding and for 1 to 2 h
afterward to minimize incidence of nosocomial aspiration pneumonia and to allow gravity to help propel
the food. Tube feedings are given in boluses several times a day or by continuous infusion.


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Bolus feeding
is more physiologic and may be preferred for patients with diabetes. Continuous infusion is necessary if
boluses cause nausea.


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[
Table 3-2. Complications of Enteral Tube Nutrition]
For bolus feeding, total daily volume is divided into 4 to 6 separate feedings, which are injected through
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support
71


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the tube with a syringe or infused by gravity from an elevated bag. After feedings, the tube is flushed with
water to prevent clogging. Nasogastric or nasoduodenal tube feeding
 often causes diarrhea initially; thus, feedings are usually
started with small amounts of dilute preparations and increased as tolerated. Most formulas contain 0.5,
1, or 2 kcal/mL.


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Formulas with higher caloric concentration (less water per calorie) may cause decreased
gastric emptying and thus higher gastric residuals than when more dilute formulas with the same number
of calories are used. Initially, a 1-kcal/mL commercially prepared solution may be given undiluted at 50
mL/h or, if patients have not been fed for a while, at 25 mL/h.


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Usually, these solutions do not supply
enough water, particularly if vomiting, diarrhea, sweating, or fever has increased water loss. Extra water
is supplied as boluses via the feeding tube or IV. After a few days, the rate or concentration can be
increased as needed to meet caloric and water needs. Jejunostomy tube feeding
 requires greater dilution and smaller volumes. Feeding usually begins at a
concentration of ≤ 0.5 kcal/mL and a rate of 25 mL/h.


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After a few days, concentrations and volumes can
be increased to eventually meet caloric and water needs. Usually, the maximum that can be tolerated is
0.8 kcal/mL at 125 mL/h, providing 2400 kcal/day. Complications:
 Complications are common and can be serious (see 
Table 3-2
).


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Total Parenteral Nutrition
Parenteral nutrition is by definition given IV. Partial parenteral nutrition
 supplies only part of daily nutritional requirements, supplementing oral
intake. Many hospitalized patients are given dextrose or amino acid solutions by this method. Total parenteral nutrition
 (TPN) supplies all daily nutritional requirements. TPN can be used in the
hospital or at home. Because TPN solutions are concentrated and can cause thrombosis of peripheral
veins, a central venous catheter is usually required. Parenteral nutrition should not be used routinely in patients with an intact GI tract.


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Compared with enteral
nutrition, it causes more complications, does not preserve GI tract structure and function as well, and is
more expensive. Indications:
 TPN may be the only feasible option for patients who do not have a functioning GI tract or
who have disorders requiring complete bowel rest, such as the following:
• Some stages of Crohn's disease or ulcerative colitis
• Bowel obstruction
• Certain pediatric GI disorders (eg, congenital GI anomalies, prolonged diarrhea regardless of its cause)
• Short bowel syndrome due to surgery
Nutritional content:
 TPN requires water (30 to 40 mL/kg/day), energy (30 to 60 kcal/kg/day, depending
on energy expenditure), amino acids (1 to 2.0 g/kg/day, depending on the degree of catabolism), essential
fatty acids, vitamins, and minerals (see
Table 3-3
). Children who need TPN may have different fluid requirements and need more energy (up to
120 kcal/kg/day) and amino acids (up to 2.5 or 3.5 g/kg/day). Basic TPN solutions are prepared using sterile techniques, usually in liter batches according to standard
formulas. Normally, 2 L/day of the standard solution is needed.


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Solutions may be modified based on
laboratory results, underlying disorders, hypermetabolism, or other factors. Most calories are supplied as carbohydrate. Typically, about 4 to 5 mg/kg/day of dextrose is given. Standard solutions contain up to about 25% dextrose, but the amount and concentration depend on other
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support
72


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factors, such as metabolic needs and the proportion of caloric needs that are supplied by lipids. Commercially available lipid emulsions are often added to supply essential fatty acids and triglycerides;
20 to 30% of total calories are usually supplied as lipids. However, withholding lipids and their calories
may help obese patients mobilize endogenous fat stores, increasing insulin sensitivity. Solutions:
 Many solutions are commonly used.


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Electrolytes can be added to meet the patient's needs. Solutions vary depending on other disorders present and patient age, as for the following:
• For renal insufficiency not being treated with dialysis or for liver failure: Reduced protein content and a
high percentage of essential amino acids
• For heart or kidney failure: Limited volume (liquid) intake
• 
For respiratory failure: A lipid emulsion that provides most of nonprotein calories to minimize CO
2
production by carbohydrate metabolism
• For neonates: Lower dextrose concentrations (17 to 18%)
Beginning TPN administration:
 Because the central venous catheter needs to remain in place for a
long time, strict sterile technique must be used during insertion and maintenance. The TPN line should
not be used for any other purpose.


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External tubing should be changed every 24 h with the first bag of the
day. In-line filters have not been shown to decrease complications. Dressings should be kept sterile and
are usually changed every 48 h using strict sterile techniques. If TPN is given outside the hospital,
patients must be taught to recognize symptoms of infection, and qualified home nursing must be
arranged. The solution is started slowly at 50% of the calculated requirements, using 5% dextrose to make up the
balance of fluid requirements. Energy and nitrogen should be given simultaneously. The amount of
regular insulin given (added directly to the TPN solution) depends on the plasma glucose level; if the
level is normal and the final solution contains 25% dextrose, the usual starting dose is 5 to 10 units of
regular insulin/L of TPN fluid. Monitoring:
 Progress should be followed on a flowchart.


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An interdisciplinary nutrition team, if available,
should monitor patients. Weight, CBC, electrolytes, and BUN should be monitored often (eg, daily for
inpatients). Plasma glucose should be monitored every 6 h until patients and glucose levels become
stable. Fluid intake and output should be monitored continuously. When patients become stable, blood
tests can be done much less often. Liver function tests should be done. Plasma proteins (eg, serum albumin, possibly transthyretin or retinol-
binding protein), PT, plasma and urine osmolality, and Ca, Mg, and phosphate should be measured
twice/wk. Changes in transthyretin and retinol-binding protein reflect overall clinical status rather than
nutritional status alone. If possible, blood tests should not be done during glucose infusion.


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Full nutritional
assessment (including BMI calculation and anthropometric measurements—see pp. 11
 and 
58
) should be
repeated at 2-wk intervals.


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[
Table 3-3. Basic Adult Daily Requirements for Total Parenteral Nutrition]
Catheter-related sepsis occurs in about ≥ 50% of patients. Glucose abnormalities (hyperglycemia or
hypoglycemia) or liver dysfunction occurs in > 90% of patients.


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Glucose abnormalities
 are common. Hyperglycemia can be avoided by monitoring plasma glucose
often, adjusting the insulin dose in the TPN solution and giving subcutaneous insulin as needed. Hypoglycemia can be precipitated by suddenly stopping constant concentrated dextrose infusions. Treatment depends on the degree of hypoglycemia. Short-term hypoglycemia may be reversed with 50%
dextrose IV; more prolonged hypoglycemia may require infusion of 5 or 10% dextrose for 24 h before
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support
73


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resuming TPN via the central venous catheter. Hepatic complications
 include liver dysfunction, painful hepatomegaly, and hyperammonemia. They can
develop at any age but are most common among infants, particularly premature ones (whose liver is
immature). • Liver dysfunction may be transient, evidenced by increased transaminases, bilirubin, and alkaline
phosphatase; it commonly occurs when TPN is started. Delayed or persistent elevations may result
from excess amino acids.


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Pathogenesis is unknown, but cholestasis and inflammation may contribute. Progressive fibrosis occasionally develops. Reducing protein delivery may help. • Painful hepatomegaly suggests fat accumulation; carbohydrate delivery should be reduced. • Hyperammonemia can develop in infants, causing lethargy, twitching, and generalized seizures. Arginine
supplementation at 0.5 to 1.0 mmol/kg/day can correct it. If infants develop any hepatic complication, limiting amino acids to 1.0 g/kg/day may be necessary. Abnormalities of serum electrolytes and minerals
 should be corrected by modifying subsequent
infusions or, if correction is urgently required, by beginning appropriate peripheral vein infusions.


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Vitamin
and mineral deficiencies are rare when solutions are given correctly. Elevated BUN may reflect
dehydration, which can be corrected by giving free water as 5% dextrose via a peripheral vein. Volume overload
 (suggested by > 1 kg/day weight gain) may occur when patients have high daily
energy requirements and thus require large fluid volumes. Metabolic bone disease
, or bone demineralization (osteoporosis or osteomalacia), develops in some
patients given TPN for > 3 mo.


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The mechanism is unknown. Advanced disease can cause severe
periarticular, lower-extremity, and back pain. Temporarily or permanently stopping TPN is the only known
treatment. Adverse reactions to lipid emulsions
 (eg, dyspnea, cutaneous allergic reactions, nausea, headache,
back pain, sweating, dizziness) are uncommon but may occur early, particularly if lipids are given at > 1.0
kcal/kg/h. Temporary hyperlipidemia may occur, particularly in patients with kidney or liver failure;
treatment is usually not required. Delayed adverse reactions to lipid emulsions include hepatomegaly, mild
elevation of liver enzymes, splenomegaly, thrombocytopenia, leukopenia, and, especially in premature
infants with respiratory distress syndrome, pulmonary function abnormalities. Temporarily or permanently
slowing or stopping lipid emulsion infusion may prevent or minimize these adverse reactions. Gallbladder complications
 include cholelithiasis, gallbladder sludge, and cholecystitis. These
complications can be caused or worsened by prolonged gallbladder stasis. Stimulating contraction by
providing about 20 to 30% of calories as fat and stopping glucose infusion several hours a day is helpful.


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Treatment with metronidazole, ursodeoxycholic acid, phenobarbital, or
cholecystokinin helps some patients with cholestasis. Nutritional Support for Dying or Severely Demented Patients
Anorexia or loss of appetite is common among dying patients (see p.


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Behavioral measures (eg,
using flexible feeding schedules, feeding slowly, giving small portions or favorite or strongly flavored
foods) can often increase oral intake. A small amount of a favorite alcoholic drink, given 30 min before
meals, may also help. Certain antidepressants, megestrol acetate, and dronabinol may stimulate appetite. Metoclopramide enhances gastric emptying, but it may take 1 to 2 wk to reach peak effectiveness. Advanced dementia eventually leads to inability to eat; sometimes affected patients are given tube
feedings.


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However, there is no convincing evidence that tube feedings prolong life, provide comfort,
improve function, or prevent complications (eg, aspiration, pressure ulcers). Tube feedings and parenteral nutrition cause discomfort and are usually not indicated for patients who
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support
74


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are dying or too demented to eat. Forgoing nutritional support may be difficult for family members to
accept, but they should understand that patients are usually more comfortable eating and drinking as they
choose. Sips of water and easy-to-swallow foods may be useful. Supportive care, including good oral
hygiene (eg, brushing the teeth, moistening the oral cavity with swabs and ice chips as needed, applying
lip salve), can physically and psychologically comfort the patients and the family members who provide
the care. Counseling may help family members who are dealing with anxieties about whether to use invasive
nutritional support.


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Chapter 4. Vitamin Deficiency, Dependency, and Toxicity
Introduction
Vitamins may be fat soluble (vitamins A, D, E, and K) or water soluble (B vitamins and vitamin C). The B
vitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B
2
), thiamin (B
1
), B
6
 (eg, pyridoxine),
and B
12
 (cobalamins). For dietary requirements, sources, functions, effects of deficiencies and toxicities,
blood levels, and usual therapeutic dosages for vitamins, see
Tables 4-1
 and
4-2
.


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Dietary requirements for vitamins (and other nutrients) are expressed as daily recommended intake (DRI). There are 3 types of DRI:
• 
Recommended daily allowance (RDA):
 RDAs are set to meet the needs of 97 to 98% of healthy
people. • 
Adequate intake (AI):
 When data to calculate an RDA are insufficient, AIs are based on observed or
experimentally determined estimates of nutrient intake by healthy people. • 
Tolerable upper intake level (UL):
 ULs are the largest amount of a nutrient that most adults can
ingest daily without risk of adverse health effects. In developed countries, vitamin deficiencies result mainly from poverty, food faddism, drugs (see p.


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7
 and
Table 4-3
), alcoholism, or prolonged and inadequately supplemented parenteral feeding. Mild vitamin
deficiency is common among frail and institutionalized elderly people who have protein-energy
undernutrition. In developing countries, deficiencies can result from lack of access to nutrients.


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Deficiencies of water-soluble vitamins (except vitamin B
12
) may develop after weeks to months of
undernutrition. Deficiencies of fat-soluble vitamins and of vitamin B
12
 take > 1 yr to develop because the
body stores them in relatively large amounts. Intake of vitamins sufficient to prevent classic vitamin
deficiencies (like scurvy or beriberi) may not be adequate for optimum health. This area remains one of
controversy and active research. Vitamin dependency results from a genetic defect involving metabolism of a vitamin. In some cases,
vitamin doses as high as 1000 times the DRI improve function of the altered metabolic pathway. Vitamin
toxicity (hypervitaminosis) usually results from taking megadoses of vitamin A, D, C, B
6
, or niacin. Because many people eat irregularly, foods alone may provide suboptimal amounts of some vitamins.


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Because of this risk, routine
daily multivitamin supplements are sometimes recommended. Biotin and Pantothenic Acid
Biotin acts as a coenzyme for carboxylation reactions essential to fat and carbohydrate metabolism. Adequate intake for adults is 30 
μ
g/day. Pantothenic acid is widely distributed in foods; it is an essential
component of coenzyme A. Adults probably require about 5 mg/day. A beneficial role for pantothenic acid
supplementation in lipid metabolism, RA, or athletic performance remains unproved. Isolated deficiency of
biotin or pantothenic acid virtually never occurs. Folate
Folate (folic acid) is now added to enriched grain foods in the US. Folate is also plentiful in various plant
foods and meats, but its bioavailability is greater when it is in supplements
[
Table 4-1. Recommended Daily Intakes for Vitamins]
or enriched foods than when it occurs naturally in food.


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Folates are involved in RBC maturation and synthesis of purines and pyrimidines. They are required for
development of the fetal nervous system. Absorption occurs in the duodenum and upper jejunum. Enterohepatic circulation of folate occurs.


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Folate supplements
[
Table 4-2. Sources, Functions, and Effects of Vitamins]
do not protect against coronary artery disease or stroke (by lowering homocysteine levels); their role in
reducing the risk of various cancers is unclear. The upper limit for folate intake is 1000 
μ
g; higher doses
(up to 5 mg) are recommended for women who have had a baby with a neural tube defect. Folate is
essentially nontoxic.


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Folate Deficiency
Folate deficiency is common. It may result from inadequate intake, malabsorption, or use of various drugs. Deficiency causes megaloblastic anemia (indistinguishable from that due to vitamin B
12
 deficiency). Maternal deficiency increases the risk of neural tube birth defects.


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Diagnosis requires laboratory testing
to confirm. Measurement of neutrophil hypersegmentation is sensitive and readily available. Treatment
with oral folate is usually successful.


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Etiology and Pathophysiology
The most common causes are inadequate intake (usually in patients with undernutrition or alcoholism),
increased demand (eg, due to pregnancy or breastfeeding), and impaired absorption (eg, in tropical
sprue, due to certain drugs). Deficiency can also result from inadequate bioavailability and increased
excretion (see
Table 4-4
). Prolonged cooking destroys folate, predisposing to inadequate intake. Intake is sometimes barely
adequate (eg, in alcoholics). Liver stores provide only a several-month supply. Alcohol interferes with folate absorption, metabolism, renal excretion, and enterohepatic reabsorption, as
well as intake. 5-Fluorouracil, metformin, methotrexate, phenobarbital, phenytoin, sulfasalazine,
triamterene, and trimethoprim impair folate metabolism. In the US, many dietary staples (eg, cereals, grain products) are routinely enriched with folate, tending to
reduce risk of deficiency.


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[
Table 4-3. Potential Vitamin-Drug Interactions]
Symptoms and Signs
Folate deficiency may cause glossitis, diarrhea, depression, and confusion. Anemia may develop
insidiously and, because of compensatory mechanisms, be more severe than symptoms suggest.


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Folate deficiency during pregnancy increases the risk of fetal neural tube defects and perhaps other brain
defects (see p. 2992
). Diagnosis
• CBC and serum vitamin B
12
 and folate levels
CBC may indicate megaloblastic anemia indistinguishable from that of vitamin B
12
 deficiency. If serum
folate is < 3 
μ
g/L or ng/mL (< 7 nmol/L), deficiency is likely.


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Serum folate reflects folate status unless
intake has recently increased or decreased. If intake has changed, erythrocyte (RBC) folate level better
reflects tissue stores. A level of < 140 
μ
g/L or ng/mL (< 305 nmol/L) indicates inadequate status. Also, an
increase in the homocysteine level suggests tissue folate deficiency (but the level is also affected by
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
77


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vitamin B
12
 and vitamin B
6
 levels, renal insufficiency, and genetic factors). A normal methylmalonic acid
(MMA) level may differentiate folate deficiency from vitamin B
12
 deficiency because MMA levels rise in
vitamin B
12
 deficiency but not in folate deficiency. Treatment
• Supplemental oral folate
Folate 400 to 1000 
μ
g po once/day replenishes tissues and is usually successful even if deficiency has
resulted from malabsorption.


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[
Table 4-4. Causes of Folate Deficiency]
(CAUTION: 
In patients with megaloblastic anemia, vitamin B
12
 deficiency must be ruled out before
treating with folate. If vitamin B
12
 deficiency is present, folate supplementation can alleviate the
anemia but does not reverse and may even worsen neurologic deficits
.) For pregnant women, the
recommended daily allowance (RDA) is 600 
μ
g/day. For women who have had a fetus or infant with a
neural tube defect, the recommended dose is 1000 to 5000 
μ
g/day.


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Niacin
Niacin (nicotinic acid, nicotinamide) derivatives include nicotinamide adenine dinucleotide (NAD) and
nicotinamide adenine dinucleotide phosphate (NADP), which are coenzymes in oxidation-reduction
reactions.


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They are vital in cell metabolism. Because dietary tryptophan can be metabolized to niacin,
foods rich in tryptophan (eg, dairy products) can compensate for inadequate dietary niacin. Niacin Deficiency
Dietary niacin deficiency (causing pellagra) is uncommon in developed countries. Clinical
manifestations include the "three Ds": localized pigmented rash (dermatitis); gastroenteritis
(diarrhea); and widespread neurologic deficits, including cognitive decline (dementia). Diagnosis is usually clinical, and dietary supplementation (oral or, if needed, IM) is usually
successful. Etiology
Primary deficiency results from extremely inadequate intake of both niacin and tryptophan, which usually
occurs in areas where maize (Indian corn) constitutes a substantial part of the diet. Bound niacin, found in
maize, is not assimilated in the GI tract unless it has been previously treated with alkali, as when tortillas
are prepared. Corn protein is also deficient in tryptophan. The high incidence of pellagra in India among
people who eat millet with a high leucine content has led to the hypothesis that amino acid imbalance may
contribute to deficiency. Deficiencies of protein and many B vitamins commonly accompany primary niacin
deficiency.


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Secondary deficiency may be due to diarrhea, cirrhosis, or alcoholism. Pellagra also may occur in
carcinoid syndrome (tryptophan is diverted to form 5-hydroxytryptophan and serotonin) and in Hartnup
disease (absorption of tryptophan by the intestine and kidneys is defective). Symptoms and Signs
Pellagra is characterized by skin, mucous membrane, CNS, and GI symptoms. Advanced pellagra can
cause a symmetric photosensitive rash, stomatitis, glossitis, diarrhea, and mental aberrations. Symptoms
may appear alone or in combination.


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Skin symptoms
 include several types of lesions, which are usually bilaterally symmetric. The distribution
of lesions—at pressure points or sun-exposed skin—is more pathognomonic than the form of the lesions. Lesions can develop in a glovelike distribution on the hands (pellagrous glove) or in a boot-shaped
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
78


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distribution on the feet and legs (pellagrous boot). Sunlight causes Casal's necklace and butterfly-shaped
lesions on the face. Mucous membrane symptoms
 affect primarily the mouth but may also affect the vagina and urethra.


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Glossitis and stomatitis characterize acute deficiency. As the deficiency progresses, the tongue and oral
mucous membranes become reddened, followed by pain in the mouth, increased salivation, and edema of
the tongue. Ulcerations may appear, especially under the tongue, on the mucosa of the lower lip, and
opposite the molar teeth. GI symptoms
 early in the deficiency include burning in the pharynx and esophagus and abdominal
discomfort and distention. Constipation is common.


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Diarrhea is often bloody because of bowel hyperemia and ulceration. CNS symptoms
 include psychosis, encephalopathy (characterized by impaired consciousness), and
cognitive decline (dementia). Psychosis is characterized by memory impairment, disorientation, confusion,
and confabulation; the predominant symptom may be excitement, depression, mania, delirium, or
paranoia. Diagnosis
• Clinical evaluation
Diagnosis is clinical and may be straightforward when skin and mouth lesions, diarrhea, delirium, and
dementia occur simultaneously.


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More often, the presentation is not so specific. Differentiating the CNS
changes from those in thiamin deficiency is difficult. A history of a diet lacking niacin and tryptophan may
help establish the diagnosis. A favorable response to treatment with niacin can usually 
confirm it.


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If
available, laboratory testing can help confirm the diagnosis, particularly when the diagnosis is otherwise
unclear. Urinary excretion of N
1
-methylnicotinamide (NMN) is decreased; < 0.8 mg/day (< 5.8 
μ
mol/day)
suggests a niacin deficiency. Treatment
• Nicotinamide and other nutrients
Because multiple deficiencies are common, a balanced diet, including other B vitamins (particularly
riboflavin and pyridoxine), is needed. Nicotinamide is usually used to treat deficiency, because
nicotinamide, unlike nicotinic acid (the most common form of niacin), does not cause flushing, itching,
burning, or tingling sensations. Nicotinamide is given in doses ranging from 40 to 250 mg/day po in
divided doses 3 to 4 times a day. Niacin Toxicity
Niacin (nicotinic acid) in large amounts is sometimes used to lower low-density lipoprotein
(LDL) cholesterol and triglyceride levels and to increase high-density lipoprotein (HDL)
cholesterol levels. Symptoms may include flushing and, rarely, hepatotoxicity. Immediate- and sustained-release preparations of niacin (but not nicotinamide) may improve lipid levels. Flushing, which is prostaglandin-mediated, is more common with immediate-release preparations. It may
be more intense after alcohol ingestion, aerobic activity, sun exposure, and consumption of spicy foods. Flushing is minimized if niacin is taken after meals or if aspirin (325 mg) is taken 30 to 45 min before
niacin. The chance of severe flushing can be reduced by starting immediate-release niacin at a low dose
(eg, 50 mg tid) and increasing it very slowly. At intermediate doses (1000 mg/day), triglyceride levels
decrease 15 to 20%, and HDL cholesterol levels increase 15 to 30%. Reductions in LDL cholesterol are
modest (< 10%). Higher doses of niacin (3000 mg/day) reduce LDL cholesterol 15 to 20% but may cause
jaundice, abdominal discomfort, blurred vision, worsening of hyperglycemia, and precipitation of
preexisting gout. People with a liver disorder probably should not take high-dose niacin.


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Some authorities
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
79


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recommend checking levels of uric acid, serum glucose, and plasma transaminases every 6 to 8 wk until
the dose of niacin has been stabilized. Riboflavin
Riboflavin (vitamin B
2
) is involved in carbohydrate metabolism as an essential coenzyme in many
oxidation-reduction reactions.


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Riboflavin Deficiency
Riboflavin deficiency usually occurs with other B-vitamin deficiencies. Symptoms and signs
include sore throat, lesions of the lips and mucosa of the mouth, glossitis, conjunctivitis,
seborrheic dermatitis, and normochromicnormocytic anemia. Diagnosis is usually clinical. Treatment consists of oral or, if needed, IM riboflavin. Primary riboflavin deficiency results from inadequate intake of fortified cereals, milk, and other animal
products. The most common causes of secondary deficiency are chronic diarrhea, malabsorption
syndromes, liver disorders, hemodialysis, peritoneal dialysis, long-term use of barbiturates, and chronic
alcoholism. Symptoms and Signs
The most common signs are pallor and maceration of the mucosa at the angles of the mouth (angular
stomatitis) and vermilion surfaces of the lips (cheilosis), eventually replaced by superficial linear fissures. The fissures can become infected with 
Candida albicans
, causing grayish white lesions (perleche). The
tongue may appear magenta. Seborrheic dermatitis develops, usually affecting the nasolabial folds, ears,
eyelids, and scrotum or labia majora. These areas become red, scaly, and greasy.


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Rarely, neovascularization and keratitis of the cornea occur, causing lacrimation and photophobia. Diagnosis
The lesions characteristic of riboflavin deficiency are nonspecific. Riboflavin deficiency should be
suspected if characteristic signs develop in a patient with other B vitamin deficiencies. Diagnosis can be
confirmed by a therapeutic trial or laboratory testing, usually by measuring urinary excretion of riboflavin. Treatment
Riboflavin 5 to 10 mg/day po is given until recovery. Other water-soluble vitamins should also be given.


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Thiamin
Thiamin (vitamin B
1
) is widely available in the diet. Thiamin is involved in carbohydrate, fat, amino acid,
glucose, and alcohol metabolism. Thiamin is essentially nontoxic. Thiamin Deficiency
Thiamin deficiency (causing beriberi) is most common among people subsisting on white rice
or highly refined carbohydrates in developing countries and among alcoholics. Symptoms
include diffuse polyneuropathy, high-output heart failure, and Wernicke-Korsakoff syndrome. Thiamin is given to help diagnose and treat the deficiency. Etiology
Primary thiamin deficiency is caused by inadequate intake of thiamin. It is commonly due to a diet of
highly refined carbohydrates (eg, polished rice, white flour, white sugar). It also develops when intake of
other nutrients is inadequate; it often occurs with other B vitamin deficiencies.


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Secondary thiamin deficiency is caused by increased demand (eg, due to hyperthyroidism, pregnancy,
breastfeeding, strenuous exercise, or fever), impaired absorption (eg, due to prolonged diarrhea), or
impaired metabolism (eg, due to hepatic insufficiency). In alcoholics, many mechanisms contribute to
thiamin deficiency; they include decreased intake, impaired absorption and use, increased demand, and
possibly an apoenzyme defect. Pathophysiology
Deficiency causes degeneration of peripheral nerves, thalamus, mammillary bodies, and cerebellum. Cerebral blood flow is markedly reduced, and vascular resistance is increased.


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The heart may become dilated; muscle fibers become swollen, fragmented, and vacuolized, with
interstitial spaces dilated by fluid. Vasodilation occurs and can result in edema in the feet and legs. Arteriovenous shunting of blood increases. Eventually, high-output heart failure may occur.


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Symptoms and Signs
Early symptoms are nonspecific: fatigue, irritability, poor memory, sleep disturbances, precordial pain,
anorexia, and abdominal discomfort. Dry beriberi
 refers to peripheral neurologic deficits due to thiamin deficiency. These deficits are bilateral
and roughly symmetric, occurring in a stocking-glove distribution.


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They affect predominantly the lower
extremities, beginning with paresthesias in the toes, burning in the feet (particularly severe at night),
muscle cramps in the calves, pains in the legs, and plantar dysesthesias. Calf muscle tenderness,
difficulty rising from a squatting position, and decreased vibratory sensation in the toes are early signs. Muscle wasting occurs. Continued deficiency worsens polyneuropathy, which can eventually affect the
arms. Wernicke-Korsakoff syndrome,
 which combines Wernicke's encephalopathy (see p.


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1522
) and
Korsakoff's psychosis (see p. 1523
), occurs in some alcoholics who do not consume foods fortified with
thiamin. Wernicke's encephalopathy consists of psychomotor slowing or apathy, nystagmus, ataxia,
ophthalmoplegia, impaired consciousness, and, if untreated, coma and death. It probably results from
severe acute deficiency superimposed on chronic deficiency. Korsakoff's psychosis consists of mental
confusion, dysphonia, and confabulation with impaired memory of recent events. It probably results from
chronic deficiency and may develop after repeated episodes of Wernicke's encephalopathy. Cardiovascular (wet) beriberi
 is myocardial disease due to thiamin deficiency. The first effects are
vasodilation, tachycardia, a wide pulse pressure, sweating, warm skin, and lactic acidosis.


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Vasodilation can continue,
sometimes resulting in shock. Infantile beriberi
 occurs in infants (usually by age 3 to 4 wk) who are breastfed by thiamin-deficient
mothers. Heart failure (which may occur suddenly), aphonia, and absent deep tendon reflexes are
characteristic. Because thiamin is necessary for glucose metabolism, glucose infusions may precipitate or worsen
symptoms of deficiency in thiamin-deficient people. Diagnosis
• Favorable response to thiamin
Diagnosis is usually based on a favorable response to treatment with thiamin in a patient with symptoms
or signs of deficiency. Similar bilateral lower-extremity polyneuropathies due to other disorders (eg,
diabetes, alcoholism, vitamin B
12
 deficiency, heavy metal poisoning) do not respond to thiamin. Single-
nerve neuritides (mononeuropathies—eg, sciatica) and multiple mononeuropathies (mononeuritis
multiplex) are unlikely to result from thiamin deficiency. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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Electrolytes, including Mg, should be measured to exclude other causes. For confirmation in equivocal
cases, erythrocyte transketolase activity and 24-h urinary thiamin excretion may be measured. Diagnosis of cardiovascular beriberi can be difficult if other disorders that cause heart failure are present. A therapeutic trial of thiamin can help.


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Treatment
• Supplemental thiamin, with dose based on clinical manifestations
Ensuring that dietary supplies of thiamin are adequate is important regardless of symptoms. Because IV
glucose can worsen thiamin deficiency, alcoholics and others at risk of thiamin deficiency should receive
IV thiamin 100 mg before receiving IV glucose solutions. For mild polyneuropathy, thiamin 10 to 20 mg po once/day is given for 2 wk. For moderate or advanced
neuropathy, the dose is 20 to 30 mg/day; it should be continued for several weeks after symptoms
disappear. For edema and congestion due to cardiovascular beriberi, thiamin 100 mg IV once/day is given
for several days. Heart failure is also treated. For Wernicke-Korsakoff syndrome, thiamin 50 to 100 mg IM or IV bid must usually be given for several
days, followed by 10 to 20 mg once/day until a therapeutic response is obtained. Anaphylactic reactions
to IV thiamin are rare. Symptoms of ophthalmoplegia may resolve in a day; improvement in patients with
Korsakoff psychosis may take 1 to 3 mo. Recovery from neurologic deficits is often incomplete in
Wernicke-Korsakoff syndrome and in other forms of thiamin deficiency. Because thiamin deficiency often occurs with other B vitamin deficiencies, multiple water-soluble vitamins
are usually given for several weeks. Patients should continue to consume a nutritious diet, supplying 1 to
2 times the daily recommended intake of vitamins; all alcohol intake should stop.


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Vitamin A
Vitamin A (retinol) is required for the formation of rhodopsin, a photoreceptor pigment in the retina. Vitamin
A helps maintain epithelial tissues. Normally, the liver stores 80 to 90% of the body's vitamin A.


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To use
vitamin A, the body releases it into the circulation bound to prealbumin (transthyretin) and retinol-binding
protein. β
-Carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables
and deep- or bright-colored fruits, are converted to vitamin A. Carotenoids are absorbed better from
vegetables when they are cooked or homogenized and served with some fats or oils. Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A
activity than preformed vitamin A; 1 
μ
g retinol = 3.33 IU. Synthetic vitamin analogs (retinoids) are being used increasingly in dermatology.


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The possible protective
role of 
β
-carotene, retinol, and retinoids against some epithelial cancers is under study. However, risk of
certain cancers may be increased after 
β
-carotene supplementation. Vitamin A Deficiency
Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders.


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Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects
(eg, xerophthalmia, night blindness). Diagnosis is based on typical ocular findings and low
vitamin A levels. Treatment consists of vitamin A given orally or, if symptoms are severe or
malabsorption is the cause, parenterally. Etiology
Primary vitamin A deficiency is usually caused by prolonged dietary deprivation. It is endemic in areas
such as southern and eastern Asia, where rice, devoid of 
β
-carotene, is the staple food.


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Xerophthalmia
due to primary deficiency is a common cause of blindness among young children in developing countries. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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Secondary vitamin A deficiency may be due to decreased bioavailability of provitamin A carotenoids or to
interference with absorption, storage, or transport of vitamin A. Interference with absorption or storage is
likely in sprue, cystic fibrosis, pancreatic insufficiency, duodenal bypass, chronic diarrhea, bile duct
obstruction, giardiasis, and cirrhosis. Vitamin A deficiency is common in prolonged protein-energy
undernutrition not only because the diet is deficient but also because vitamin A storage and transport is
defective. In children with complicated measles, vitamin A can shorten the duration of the disorder and
reduce the severity of symptoms and risk of death. Symptoms and Signs
Impaired dark adaptation of the eyes, which can lead to night blindness, is an early symptom.


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Xerophthalmia (which is nearly pathognomonic) results from keratinization of the eyes. It involves drying
(xerosis) and thickening of the conjunctivae and corneas. Superficial foamy patches composed of
epithelial debris and secretions on the exposed bulbar conjunctiva (Bitot's spots) develop. In advanced
deficiency, the cornea becomes hazy and can develop erosions, which can lead to its destruction
(keratomalacia). Keratinization of the skin and of the mucous membranes in the respiratory, GI, and urinary tracts can
occur.


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Immunity
is generally impaired. The younger the patient, the more severe are the effects of vitamin A deficiency. Growth retardation and
infections are common among children. Mortality rate can exceed 50% in children with severe vitamin A
deficiency. Diagnosis
• Serum retinol levels, clinical evaluation, and response to vitamin A
Ocular findings suggest the diagnosis. Dark adaptation can be impaired in other disorders (eg, zinc
deficiency, retinitis pigmentosa, severe refractive errors, cataracts, diabetic retinopathy). If dark
adaptation is impaired, rod scotometry and electroretinography are done to determine whether vitamin A
deficiency is the cause. Serum levels of retinol are measured. Normal range is 28 to 86 
μ
g/dL (1 to 3 
μ
mol/L). However, levels
decrease only after the deficiency is advanced because the liver contains large stores of vitamin A. Also,
decreased levels may result from acute infection, which causes retinol-binding protein and transthyretin
(also called prealbumin) levels to decrease transiently. A therapeutic trial of vitamin A may help confirm
the diagnosis.


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Prevention
The diet should include dark green leafy vegetables, deep- or bright-colored fruits (eg, papayas,
oranges), carrots, and yellow vegetables (eg, squash, pumpkin). Vitamin A-fortified milk and cereals, liver,
egg yolks, and fish liver oils are helpful.


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Carotenoids are absorbed better when consumed with some
dietary fat. If milk allergy is suspected in infants, they should be given adequate vitamin A in formula
feedings. In developing countries, prophylactic supplements of vitamin A palmitate in oil 60,000 RAE
(200,000 IU) po every 6 mo are advised for all children between 1 and 5 yr of age; infants < 6 mo can be
given a one-time dose of 15,000 RAE (50,000 IU), and those aged 6 to 12 mo can be given a one-time
dose of 30,000 RAE (100,000 IU). Treatment
• Vitamin A palmitate
Dietary deficiency is traditionally treated with vitamin A palmitate in oil 60,000 IU po once/day for 2 days,
followed by 4500 IU po once/day. If vomiting or malabsorption is present or xerophthalmia is probable, a
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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dose of 50,000 IU for infants < 6 mo, 100,000 IU for infants 6 to 12 mo, or 200,000 IU for children > 12 mo
and adults should be given for 2 days, with a third dose at least 2 wk later. The same doses are
recommended for infants and children with complicated measles. Infants born of HIV-positive mothers
should receive 50,000 IU (15,000 RAE) within 48 h of birth. Prolonged daily administration of large doses,
especially to infants, must be avoided because toxicity may result. For pregnant or breastfeeding women, prophylactic or therapeutic doses should not exceed 10,000 IU
(3000 RAE)/day to avoid possible damage to the fetus or infant. Vitamin A Toxicity
Vitamin A toxicity can be acute (usually due to accidental ingestion by children) or chronic. Both
types usually cause headache and increased intracranial pressure. Acute toxicity also causes
nausea and vomiting. Chronic toxicity also causes changes in skin, hair, and nails; abnormal
liver test results; and, in a fetus, birth defects. Diagnosis is usually clinical.


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Unless birth defects
are present, adjusting the dose almost always leads to complete recovery. Acute vitamin A toxicity in children may result from taking large doses (> 100,000 RAE [> 300,000 IU]),
usually accidentally. In adults, acute toxicity has occurred when arctic explorers ingested polar bear or
seal livers, which contain several million units of vitamin A. Chronic toxicity in older children and adults usually develops after doses of > 30,000 RAE (> 100,000
IU)/day have been taken for months. Megavitamin therapy is a possible cause, as are massive daily
doses (50,000 to 120,000 RAE [150,000 to 350,000 IU]) of vitamin A 
or its metabolites, which are
sometimes given for nodular acne or other skin disorders. Adults who consume > 1500 RAE (> 4500
IU)/day of vitamin A may develop osteoporosis. Infants who are given excessive doses (6,000 to 20,000
RAE [18,000 to 60,000 IU]/day) of water-miscible vitamin A may develop toxicity within a few weeks. Birth
defects occur in children of women receiving isotretinoin (which is related to vitamin A) for acne treatment
during pregnancy. Although carotene is converted to vitamin A in the body, excessive ingestion of carotene causes
carotenemia, not vitamin A toxicity.


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Carotenemia is usually asymptomatic but may lead to carotenodermia,
in which the skin becomes yellow. When taken as a supplement, 
β
-carotene has been associated with
increased cancer risk; risk does not seem to increase when carotenoids are consumed in fruits and
vegetables. Symptoms and Signs
Although symptoms may vary, headache and rash usually develop during acute or chronic toxicity.


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Acute
toxicity causes increased intracranial pressure. Drowsiness, irritability, abdominal pain, nausea, and
vomiting are common. Sometimes the skin subsequently peels. Early symptoms of chronic toxicity are sparsely distributed, coarse hair; alopecia of the eyebrows; dry,
rough skin; dry eyes; and cracked lips. Later, severe headache, pseudotumor cerebri, and generalized
weakness develop.


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Cortical hyperostosis of bone and arthralgia may occur, especially in children. Fractures may occur easily, especially in the elderly. In children, toxicity can cause pruritus, anorexia, and
failure to thrive.


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Hepatomegaly and splenomegaly may occur. In carotenodermia, the skin (but not the sclera) becomes deep yellow, especially on the palms and soles. Diagnosis
• Clinical evaluation
Diagnosis is clinical.


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However, if clinical diagnosis is
equivocal, laboratory testing may help. In vitamin A toxicity, fasting serum retinol levels may increase from
normal (28 to 86 
μ
g/dL [1 to 3 
μ
mol/L]) to > 100 
μ
g/dL (> 3.49 
μ
mol/L), sometimes to > 2000 
μ
g/dL (> 69.8
μ
mol/L). Hypercalcemia is common.


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The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
84


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Differentiating vitamin A toxicity from other disorders may be difficult. Carotenodermia may also occur in
severe hypothyroidism and anorexia nervosa, possibly because carotene is converted to vitamin A more
slowly. Prognosis
Complete recovery usually occurs if vitamin A ingestion stops.


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Symptoms and signs of chronic toxicity
usually disappear within 1 to 4 wk. However, birth defects in the fetus of a mother who has taken
megadoses of vitamin A are not reversible.


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Treatment
Vitamin A is stopped. Vitamin B
6
Vitamin B
6
 includes a group of closely related compounds: pyridoxine, pyridoxal, and pyridoxamine. They
are metabolized in the body to pyridoxal phosphate, which acts as a coenzyme in many important
reactions in blood, CNS, and skin metabolism. Vitamin B
6
 is important in heme and nucleic acid
biosynthesis and in lipid, carbohydrate, and amino acid metabolism. Vitamin B
6
 Deficiency and Dependency
Because vitamin B
6
 is present in most foods, dietary deficiency is rare.


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Secondary deficiency
may result from various conditions. Symptoms can include peripheral neuropathy, a pellagra-
like syndrome, anemia, and seizures, which, particularly in infants, may not resolve when
treated with anticonvulsants. Impaired metabolism (dependency) is rare; it causes various
symptoms, including seizures, intellectual disability, and anemia. Diagnosis is usually clinical;
no laboratory test readily assesses vitamin B
6
 status.


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Treatment consists of giving oral vitamin
B
6
 and, when possible, treating the cause. Dietary deficiency, though rare, can develop because extensive processing can deplete foods of vitamin
B
6
. Secondary deficiency most often results from protein-energy undernutrition, malabsorption,
alcoholism, use of pyridoxine-inactivating drugs (eg, anticonvulsants, isoniazid, cycloserine, hydralazine,
corticosteroids, penicillamine), or excessive loss. Rarely, it results from increased metabolic demand (eg,
in hyperthyroidism). Rare inborn errors of metabolism can affect pyridoxine metabolism. The role of vitamin B
6
 deficiency in increasing plasma homocysteine levels and in contributing to vascular
disorders is under study. Symptoms and Signs
Deficiency causes a pellagra-like syndrome, with seborrheic dermatitis, glossitis, and cheilosis, and, in
adults, can cause depression, confusion, EEG abnormalities, and seizures. Rarely, deficiency or
dependency causes seizures in infants.


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Seizures, particularly in infants, may be refractory to treatment
with anticonvulsants. Normocytic, microcytic, or sideroblastic anemia can also develop. Diagnosis
• Clinical evaluation
Vitamin B
6
 deficiency should be considered in any infant who has seizures, any patient who has seizures
refractory to treatment with anticonvulsants, and any patient with deficiencies of other B vitamins,
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
85


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Diagnosis is usually clinical. There is no single accepted laboratory test of vitamin B
6
 status; measurement of serum pyridoxal
phosphate is most common. Treatment
• Pyridoxine
• Elimination of risk factors when possible
For secondary deficiency, causes (eg, use of pyridoxine-inactivating drugs, malabsorption) should be
corrected if possible. Usually, pyridoxine 50 to 100 mg po once/day corrects the deficiency in adults. Most
people taking isoniazid should also be given pyridoxine 30 to 50 mg/day. For deficiency due to increased
metabolic demand, amounts larger than the daily recommended intake may be required. For most cases
of inborn errors of metabolism, high doses of pyridoxine may be effective. Vitamin B
6
 Toxicity
The ingestion of megadoses (> 500 mg/day) of pyridoxine (eg, taken to treat carpal tunnel syndrome or
premenstrual syndrome although efficacy is unproved) may cause peripheral neuropathy with deficits in a
stocking-glove distribution, including progressive sensory ataxia and severe impairment of position and
vibration senses. Senses of touch, temperature, and pain are less affected.


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Diagnosis is clinical. Treatment is to stop taking vitamin B
6
. Recovery is slow and, for some patients,
incomplete. Vitamin B
12
Cobalamin is a general term for compounds with biologic vitamin B
12
 activity. These compounds are
involved in nucleic acid metabolism, methyl transfer, and myelin synthesis and repair.


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They are necessary
for the formation of normal RBCs. Food-bound vitamin B
12
 is released in the stomach's acid environment and is bound to R protein
(haptocorrin). Pancreatic enzymes cleave this B
12
 complex (B
12
-R protein) in the small intestine. After
cleavage, intrinsic factor, secreted by parietal cells in the gastric mucosa, binds with vitamin B
12
. Intrinsic
factor is required for absorption of vitamin B
12
, which takes place in the terminal ileum. Vitamin B
12
 in plasma is bound to transcobalamins I and II.


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Transcobalamin II is responsible for delivering
vitamin B
12
 to tissues. The liver stores large amounts of vitamin B
12
. Enterohepatic reabsorption helps
retain vitamin B
12
. Liver vitamin B
12
 stores can normally sustain physiologic needs for 3 to 5 yr if B
12
intake stops (eg, in people who become vegans) and for months to 1 yr if enterohepatic reabsorption
capacity is absent. Large amounts of vitamin B
12
 seem to be nontoxic but are not recommended for regular use (ie, as a
general tonic).


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Vitamin B
12
 Deficiency
Dietary vitamin B
12
 deficiency usually results from inadequate absorption, but deficiency can
develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic
anemia, damage to the white matter of the spinal cord and brain, and peripheral neuropathy. Diagnosis is usually made by measuring serum vitamin B
12
 levels.


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The Schilling test helps
determine etiology. Treatment consists of oral or parenteral vitamin B
12
. Folate (folic acid)
should not be used instead of vitamin B
12
 because folate may alleviate the anemia but allow
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
86


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neurologic deficits to progress. Etiology
Inadequate vitamin B
12
 intake is possible in vegans but is otherwise unlikely. Breastfed babies of vegan
mothers may develop vitamin B
12
 deficiency by age 4 to 6 mo because their
[
Table 4-5. Causes of Vitamin B
12
 Deficiency]
liver stores (which are normally extensive) are limited and their rapid growth rate results in high demand.


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Vitamin B
12
 deficiency usually results from inadequate absorption (see 
Table 4-5
 and p. 153
), which, in
the elderly, most commonly results from decreased acid secretion. In such cases, crystalline vitamin B
12
(such as that available in vitamin supplements) can be absorbed, but food-bound vitamin B
12
 is not
liberated and absorbed normally. Inadequate absorption may occur in blind loop syndrome (with
overgrowth of bacteria) or fish tapeworm infestation; in these cases, bacteria or parasites use ingested
vitamin B
12
 so that less is available for absorption. Vitamin B
12
 absorption may be inadequate if ileal
absorptive sites are destroyed by inflammatory bowel disease or are surgically removed. Less common
causes of inadequate vitamin B
12
 absorption include chronic pancreatitis, gastric surgery, malabsorption
syndromes, AIDS, use of certain drugs (eg, antacids, metformin), repeated exposure to nitrous oxide, and
a genetic disorder causing malabsorption in the ileum (Imerslund-Graesbeck syndrome). Pernicious anemia
 is often used synonymously with vitamin B
12
 deficiency. However, pernicious
anemia specifically refers to anemia resulting from vitamin B
12
 deficiency caused by an autoimmune
metaplastic atrophic gastritis with loss of intrinsic factor (see p. 133
).


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Patients with classic pernicious
anemia, most commonly younger adults, are at increased risk of stomach and other GI cancers. Subacute combined degeneration
 refers to degenerative changes in the nervous system due to
vitamin B
12
 deficiency; they affect mostly brain and spinal cord white matter. Demyelinating or axonal
peripheral neuropathies can occur.


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It is often more severe than its symptoms indicate because its slow
evolution allows physiologic adaptation. Occasionally, splenomegaly and hepatomegaly occur. Various GI
symptoms, including weight loss and poorly localized abdominal pain, may occur. Glossitis, usually
described as burning of the tongue, is uncommon. Neurologic symptoms develop independently from and often without hematologic abnormalities.


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In early
stages, decreased position and vibratory sensation in the extremities is accompanied by mild to moderate
weakness and hyporeflexia. In later stages, spasticity, extensor plantar responses, greater loss of position
and vibratory sensation in the lower extremities, and ataxia emerge. These deficits may develop in a
stocking-glove distribution. Tactile, pain, and temperature sensations are usually spared but may be
difficult to assess in the elderly.


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Some patients are also irritable and mildly depressed. Paranoia (megaloblastic madness), delirium,
confusion, spastic ataxia, and, at times, postural hypotension may occur in advanced cases. The
confusion may be difficult to differentiate from age-related dementias, such as Alzheimer's disease. Diagnosis
• CBC and vitamin B
12
 and folate levels
• Sometimes methylmalonic acid levels or Schilling test
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
87


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Diagnosis is based on CBC and vitamin B
12
 and folate levels. It is important to remember that severe
neurologic disease may occur without anemia or macrocytosis. CBC detects megaloblastic anemia.


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Tissue deficiency and macrocytic indexes may precede the
development of anemia. A vitamin B
12
 level < 200 pg/mL (< 145 pmol/L) indicates vitamin B
12
 deficiency. The folate level is measured because vitamin B
12
 deficiency must be differentiated from folate deficiency
as a cause of megaloblastic anemia; folate supplementation can mask vitamin B
12
 deficiency and may
alleviate megaloblastic anemia but allow the neurologic deficits to progress or even accelerate. When clinical judgment suggests vitamin B
12
 deficiency but the vitamin B
12
 level is low-normal (200 to
350 pg/mL [145 to 260 pmol/L]) or hematologic indexes are normal, other tests can be done. Measuring
serum methylmalonic acid (MMA) levels may be useful. An elevated MMA level supports vitamin B
12
deficiency but may be due to renal failure. MMA levels can also be used to monitor the response to
treatment. MMA levels remain normal in folate deficiency; homocysteine levels may be elevated with
either vitamin B
12
 or folate deficiency. Less commonly, holotranscobalamin II (transcobalamin II-B
12
complex) content is measured; when holotranscobalamin II is < 40 pg/mL (< 30 pmol/L), vitamin B
12
 is
deficient. After deficiency is diagnosed, additional tests may be indicated for younger adults but usually not for the
elderly. Unless dietary vitamin B
12
 is obviously inadequate, measurement of serum gastrin levels or
autoantibodies to intrinsic factor may be done; sensitivity and specificity of these tests may be poor. Schilling test:
 The Schilling test is useful only if diagnosing intrinsic factor deficiency is important, as in
classic pernicious anemia. This test is not necessary for most elderly patients.


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The Schilling test
measures absorption of free radiolabeled vitamin B
12
. Radiolabeled vitamin B
12
 is given orally, followed
in 1 to 6 h by 1000 
μ
g (1 mg) of parenteral vitamin B
12
, which reduces uptake of radiolabeled vitamin
B
12
 by the liver. Absorbed radiolabeled vitamin B
12
 is excreted in urine, which is collected for 24 h. The
amount excreted is measured, and the percentage of total radiolabeled vitamin B
12
 is determined. If
absorption is normal, ≥ 9% of the dose given appears in the urine. Reduced urinary excretion (< 5% if
kidney function is normal) indicates inadequate vitamin B
12
 absorption. Improved absorption with the
subsequent addition of intrinsic factor to radiolabeled vitamin B
12
 confirms the diagnosis of pernicious
anemia. The test is often difficult to do or interpret because of incomplete urine collection or renal
insufficiency. In addition, because the Schilling test does not measure absorption of protein-bound vitamin
B
12
, the test does not detect defective liberation of vitamin B
12
 from foods, which is common among the
elderly. The Schilling test repletes vitamin B
12
 and can mask deficiency, so it should be done only after all
other diagnostic tests and therapeutic trials. If malabsorption is identified, the Schilling test can be repeated after a 2-wk trial of an oral antibiotic. If
antibiotic therapy corrects malabsorption, the likely cause is intestinal overgrowth of bacteria (eg, blind-
loop syndrome). Treatment
• Supplemental vitamin B
12
Vitamin B
12
 1000 to 2000 
μ
g po can be given once/day to patients who do not have severe deficiency or
neurologic symptoms or signs.


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If the MMA level
(sometimes used to monitor treatment) does not decrease, patients may not be taking vitamin B
12
. For
more severe deficiency, vitamin B
12
 1 mg IM is usually given 1 to 4 times/wk for several weeks until
hematologic abnormalities are corrected; then it is given once/mo. Although hematologic abnormalities are usually corrected within 6 wk (reticulocyte count should improve
within 1 wk), resolution of neurologic symptoms may take much longer.


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for months or years become irreversible. In most elderly people with vitamin B
12
 deficiency and dementia,
cognition does not improve after treatment. Vitamin B
12
 treatment must be continued for life unless the
pathophysiologic mechanism for the deficiency is corrected. Infants of vegan mothers should receive supplemental vitamin B
12
 from birth. Vitamin C
Vitamin C (ascorbic acid) plays a role in collagen, carnitine, hormone, and amino acid formation. It is
essential for wound healing and facilitates recovery from burns. Vitamin C is also an antioxidant, supports
immune function, and facilitates the absorption of iron. Vitamin C Deficiency
In developed countries, vitamin C deficiency can occur as part of general undernutrition, but
severe deficiency (causing scurvy) is uncommon. Symptoms include fatigue, depression, and
connective tissue defects (eg, gingivitis, petechiae, rash, internal bleeding, impaired wound
healing).


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Diagnosis is usually clinical. Treatment consists of oral vitamin C. Severe deficiency results in scurvy, a disorder characterized by hemorrhagic manifestations and abnormal
osteoid and dentin formation. Etiology
In adults, primary deficiency is usually due to inadequate diet. The need for dietary vitamin C is increased
by febrile illnesses, inflammatory disorders (particularly diarrheal disorders), achlorhydria, smoking,
thyrotoxicosis, iron deficiency, cold or heat stress, surgery, burns, and protein deficiency. Heat (eg,
sterilization of formulas, cooking) can destroy some of the vitamin C in food. Pathophysiology
Formation of intercellular cement substances in connective tissues, bones, and dentin is defective,
resulting in weakened capillaries with subsequent hemorrhage and defects in bone and related
structures.


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Bone tissue formation becomes impaired, which, in children, causes bone lesions and poor bone growth. Fibrous tissue forms between the diaphysis and the epiphysis, and costochondral junctions enlarge. Densely calcified fragments of cartilage are embedded in the fibrous tissue. Subperiosteal hemorrhages,
sometimes due to small fractures, may occur in children or adults. Symptoms and Signs
In adults, symptoms develop after weeks to months of vitamin C depletion. Lassitude, weakness,
irritability, weight loss, and vague myalgias and arthralgias may develop early.


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Later, symptoms related to defects in connective tissues develop. Follicular hyperkeratosis, coiled hair,
and perifollicular hemorrhages may develop. Gums may become swollen, purple, spongy, and friable; they
bleed easily in severe deficiency. Eventually, teeth become loose and avulsed.


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Secondary infections may
develop. Wounds heal poorly and tear easily, and spontaneous hemorrhages may occur, especially as
ecchymoses in the skin of the lower limbs or as bulbar conjunctival hemorrhage. Other symptoms and signs include femoral neuropathy due to hemorrhage into femoral sheaths (which
may mimic deep venous thrombosis), lower-extremity edema, and painful bleeding or effusions within
joints. Diagnosis
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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• Usually, skin or gingival findings and risk factors
Diagnosis is usually made clinically in a patient who has skin or gingival signs and is at risk of vitamin C
deficiency. Laboratory confirmation may be available.


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Bleeding, coagulation, and PT
are normal. Skeletal x-rays can help diagnose childhood (but not adult) scurvy. Changes are most evident at the ends
of long bones, particularly at the knee.


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Early changes resemble atrophy. Loss of trabeculae results in a
ground-glass appearance. The cortex thins. A line of calcified, irregular cartilage (white line of Fraenkel)
may be visible at the metaphysis. A zone of rarefaction or a linear fracture proximal and parallel to the
white line may be visible as only a triangular defect at the bone's lateral margin but is specific. The
epiphysis may be compressed.


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Healing subperiosteal hemorrhages may elevate and calcify the
periosteum. Laboratory diagnosis, which requires measuring blood ascorbic acid, is sometimes done at academic
centers. Levels of < 0.6 mg/dL (< 34 
μ
mol/L) are considered marginal; levels of < 0.2 mg/dL (< 11 
μ
mol/L)
indicate vitamin C deficiency. Measurement of ascorbic acid levels in the WBC-platelet layer of
centrifuged blood is not widely available or standardized. In adults, scurvy must be differentiated from arthritis, hemorrhagic disorders, gingivitis, and protein-energy
undernutrition. Hyperkeratotic hair follicles with surrounding hyperemia or hemorrhage are almost
pathognomonic. Bleeding gums, conjunctival hemorrhages, most petechiae, and ecchymoses are
nonspecific. Treatment
• Nutritious diet with supplemental ascorbic acid
For scurvy in adults, ascorbic acid 100 to 500 mg po tid is given for 1 to 2 wk, until signs disappear, and
followed by a nutritious diet supplying 1 to 2 times the daily recommended intake. In scurvy, therapeutic
doses 
of ascorbic acid restore the functions of vitamin C in a few days. The symptoms and signs usually
disappear over 1 to 2 wk.


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Chronic gingivitis with extensive subcutaneous hemorrhage persists longer. Prevention
Vitamin C 75 mg po once/day for women and 90 mg po once/day for men prevents deficiency. Smokers
should consume an additional 35 mg/day.


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Five servings of most fruits and vegetables (recommended
daily) provide > 200 mg of vitamin C. Vitamin C Toxicity
The upper limit for vitamin C intake is 2000 mg/day. Up to 10 g/day of vitamin C are sometimes taken for
unproven health benefits, such as preventing or shortening the duration of viral infections or slowing or
reversing the progression of cancer or atherosclerosis. Such doses may acidify the urine, cause nausea
and diarrhea, interfere with the healthy antioxidant-prooxidant balance in the body, and, in patients with
thalassemia or hemochromatosis, promote iron overload. Intake below the upper limit does not have toxic
effects in healthy adults. Vitamin D
Vitamin D has 2 main forms: D
2
 (ergocalciferol) and D
3
 (cholecalciferol); the latter is the naturally
occurring form and the form used for low-dose supplementation. Vitamin D
3
 is synthesized in skin by
exposure to direct sunlight (ultraviolet B radiation) and obtained in the diet chiefly in fish liver oils and salt
water fish. In some developed countries, milk and other foods are fortified with vitamin D. Human breast
milk is low in vitamin D, containing an average of only 10% of the amount in fortified cow's milk. Requirements for vitamin D increase with age because skin synthesis declines.


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Sunscreen use and dark
skin pigmentation also reduce skin synthesis of vitamin D. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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Vitamin D is a prohormone with several active metabolites that act as hormones. Vitamin D is metabolized
by the liver to 25(OH)D, which is then converted by the kidneys to 1,25(OH)
2
D (1,25-
dihydroxycholecalciferol, calcitriol, or active vitamin D hormone). 25(OH)D, the major circulating form, has
some metabolic activity, but 1,25(OH)
2
D is the most metabolically active. The conversion to 1,25(OH)
2
D
is regulated by its own concentration, parathyroid hormone (PTH), and serum concentrations of Ca and
phosphate. [
Table 4-6. Actions of Vitamin D and its Metabolites]
Vitamin D affects many organ systems (see 
Table 4-6
), but mainly it increases Ca and phosphate
absorption from the intestine and promotes normal bone formation and mineralization. Vitamin D and
related analogs may be used to treat psoriasis, hypoparathyroidism, renal osteodystrophy, and possibly
leukemia and breast, prostate, and colon cancers; they may also be used for immunosuppression. Vitamin D Deficiency and Dependency
Inadequate exposure to sunlight predisposes to vitamin D deficiency.


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Deficiency impairs bone
mineralization, causing rickets in children and osteomalacia in adults and possibly contributing
to osteoporosis. Treatment usually consists of oral vitamin D; Ca and phosphate are
supplemented as needed.


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Rarely, hereditary disorders cause
impaired metabolism of vitamin D (dependency). Vitamin D deficiency is a common cause of rickets and osteomalacia, but these disorders may also result
from other conditions, such as various renal tubular disorders, familial hypophosphatemic (vitamin D-
resistant) rickets (see p. 2991
), chronic metabolic acidosis, hypoparathyroidism (which reduces vitamin D
absorption), inadequate dietary Ca, and disorders or drugs that impair the mineralization of bone matrix. Vitamin D deficiency causes hypocalcemia, which stimulates production of PTH, causing
hyperparathyroidism. Hyperparathyroidism increases absorption, bone mobilization, and renal
conservation of Ca but increases excretion of phosphate. As a result, the serum level of Ca may be
normal, but because of hypophosphatemia, bone mineralization is impaired. Etiology
Vitamin D deficiency may result from the following.


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Inadequate exposure or intake:
 Inadequate direct sunlight exposure (or sunscreen use) and
inadequate intake usually occur simultaneously to result in clinical deficiency. Susceptible people include
the elderly (who are often undernourished and are not exposed to enough sunlight), and certain
communities (eg, women and children who are confined to the home or who wear clothing that covers the
entire body and face). Inadequate vitamin D stores are common among the elderly, particularly those who
are house-bound, institutionalized, or hospitalized or who have had a hip fracture. Recommended direct
sunlight exposure is 5 to 15 min (suberythemal dose) to arms and legs, or face, arms and hands, at least
3 times a week. Reduced absorption:
 Malabsorption can deprive the body of dietary vitamin D; only a small amount of
25(OH)D is recirculated enterohepatically.


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Abnormal metabolism:
 Vitamin D deficiency may result from defects in the production of 25(OH)D or
1,25(OH)
2
D. People with a chronic renal disorder commonly develop rickets or osteomalacia because
renal production of 1,25 (OH)
2
D is decreased and phosphate levels are elevated. Hepatic dysfunction
can also interfere with production of active vitamin D metabolites. Type I hereditary vitamin D-dependent rickets is an autosomal recessive disorder characterized by absent
or defective conversion of 25(OH)D to 1,25(OH)
2
D in the kidneys. X-linked familial hypophosphatemia
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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reduces vitamin D synthesis in the kidneys. Many anticonvulsants and glucocorticoid use increase the
need for vitamin D supplementation. Resistance to effects of vitamin D:
 Type II hereditary vitamin D-dependent rickets has several forms
and is due to mutations in the 1,25(OH)
2
D receptor.


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In this disorder, 1,25(OH)
2
D is abundant but ineffective because the receptor is not
functional. Symptoms and Signs
Vitamin D deficiency can cause muscle aches, muscle weakness, and bone pain at any age. Vitamin D deficiency in a pregnant woman causes deficiency in the fetus. Occasionally, deficiency severe
enough to cause maternal osteomalacia results in rickets with metaphyseal lesions in neonates. In young
infants, rickets causes softening of the entire skull (craniotabes). When palpated, the occiput and
posterior parietal bones feel like a ping pong ball. In older infants with rickets, sitting and crawling are
delayed, as is fontanelle closure; there is bossing of the skull and costochondral thickening. Costochondral thickening can look like beadlike prominences along the lateral chest wall (rachitic rosary). In children 1 to 4 yr, epiphyseal cartilage at the lower ends of the radius, ulna, tibia, and fibula enlarges;
kyphoscoliosis develops, and walking is delayed.


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In older children and adolescents, walking is painful; in
extreme cases, deformities such as bowlegs and knock-knees develop. Tetany is caused by hypocalcemia and may accompany infantile or adult vitamin D deficiency. Tetany may
cause paresthesias of the lips, tongue, and fingers; carpopedal and facial spasm; and, if very severe,
seizures. Maternal deficiency can cause tetany in neonates. Osteomalacia predisposes to fractures.


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In the elderly, hip fractures may result from only minimal trauma. Diagnosis
• Levels of 25(OH)D (D
2
+D
3
)
Diagnosis may be suspected based on any of the following:
• A history of inadequate sunlight exposure or dietary intake
• Symptoms and signs of rickets, osteomalacia, or neonatal tetany
• Characteristic bone changes seen on x-ray
X-rays of the radius and ulna plus serum levels of Ca, phosphate, alkaline phosphatase, PTH, and
25(OH)D are needed to differentiate vitamin D deficiency from other causes of bone demineralization. Assessment of vitamin D status and serologic tests for syphilis can be considered for infants with
craniotabes based on the history and physical, but most cases of craniotabes resolve spontaneously. Rickets can be distinguished from chondrodystrophy because the latter is characterized by a large head,
short extremities, thick bones, and normal serum Ca, phosphate, and alkaline phosphatase levels. Tetany due to infantile rickets may be clinically indistinguishable from seizures due to other causes. Blood
tests and clinical history may help distinguish them.


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Bone changes, seen on x-rays, precede clinical signs. In rickets, changes are most evident at the lower
ends of the radius and ulna. The diaphyseal ends lose their sharp, clear outline; they are cup-shaped and
show a spotty or fringy rarefaction. Later, because the ends of the radius and ulna have become
noncalcified and radiolucent, the distance between them and the metacarpal bones appears increased. The bone matrix elsewhere also becomes more radiolucent. Characteristic deformities result from the
bones bending at the cartilage-shaft junction because the shaft is weak. As healing begins, a thin white
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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line of calcification appears at the epiphysis, becoming denser and thicker as calcification proceeds. Later, the bone matrix becomes calcified and opacified at the subperiosteal level. In adults, bone demineralization, particularly in the spine, pelvis, and lower extremities, can be seen on x-
rays; the fibrous lamellae can also be seen, and incomplete ribbonlike areas of demineralization
(pseudofractures, Looser's lines, Milkman's syndrome) appear in the cortex. Because levels of serum 25(OH)D reflect body stores of vitamin D and correlate with symptoms and signs
of vitamin D deficiency better than levels of other vitamin D metabolites, 25(OH)D (D
2
+D
3
) measurement
is generally considered the best way to diagnose deficiency.


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Goal 25(OH)D levels are 30 to 40 ng/mL
(about 75 to 100 nmol/L); whether higher levels may be beneficial remains uncertain. If the diagnosis is unclear, serum levels of 1,25(OH)
2
D and urinary Ca concentration can be measured. In
severe deficiency, serum 1,25(OH)
2
D is abnormally low, usually undetectable. Urinary Ca is low in all
forms of the deficiency except those associated with acidosis. In vitamin D deficiency, serum Ca may be low or, because of secondary hyperparathyroidism, may be
normal. Serum phosphate usually decreases, and serum alkaline phosphatase usually increases. Serum
PTH is elevated. Type I hereditary vitamin D-dependent rickets results in normal serum 25(OH)D, low serum 1,25(OH)
2
D
and Ca, and normal or low serum phosphate. Treatment
• Correction of Ca and phosphate deficiencies
• Supplemental vitamin D
Ca deficiency (which is common) and phosphate deficiency should be corrected. As long as Ca and
phosphate intake is adequate, adults with osteomalacia and children with uncomplicated rickets can be
cured by giving vitamin D 40 
μ
g (1600 IU) po once/day. Serum 25(OH)D and 1,25(OH)
2
D begin to
increase within 1 or 2 days.


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Serum Ca and phosphate increase and serum alkaline phosphatase
decreases within about 10 days. During the 3rd wk, enough Ca and phosphate are deposited in bones to
be visible on x-rays. After about 1 mo, the dose can usually be reduced gradually to the usual
maintenance level of 10 to 15 
μ
g (400 to 600 IU) once/day. If tetany is present, vitamin D should be
supplemented with IV Ca salts for up to 1 wk (see p. 841
).


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Elderly patients may need 25 to ≥ 50 
μ
g (1000
to ≥ 2000 IU) daily to maintain a 25(OH)D level > 30 ng/mL (> 75 nmol/L); this dose is higher than the
recommended daily allowance (RDA) for people > 70 yr (600 IU) and may exceed the current upper limit
of 2000 IU/day. Because rickets and osteomalacia due to defective production of vitamin D metabolites are vitamin D-
resistant, they do not respond to the doses usually effective for rickets due to inadequate intake.


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Endocrinologic evaluation is required because treatment depends on the specific defect. When 25(OH)D
production is defective, vitamin D 50 
μ
g (2000 IU) once/day increases serum levels and results in clinical
improvement. Patients with kidney disorders often need 1,25(OH)
2
D supplementation. Type I hereditary vitamin D-dependent rickets responds to 1,25(OH)
2
D 1 to 2 
μ
g po once/day. Some
patients with type II hereditary vitamin D-dependent rickets respond to very high doses (eg, 10 to 24
μ
g/day) of 1,25(OH)
2
D; others require long-term infusions of Ca. Prevention
Dietary counseling is particularly important in communities whose members are at risk of vitamin D
deficiency. Fortifying unleavened chapati flour with vitamin D (125 
μ
g/kg) has been effective among Indian
immigrants in Britain. The benefits of sunlight exposure for vitamin D status must be weighed against the
increased skin damage and skin cancer risks.


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increased skin damage and skin cancer risks. All breastfed infants should be given supplemental vitamin D 5 
μ
g (200 IU) once/day from birth to 6 mo; at
6 mo, a more diversified diet is available. For adolescents at risk, a single IM dose of ergocalciferol 2.5
mg (100,000 IU) given in the fall can maintain adequate 25(OH)D levels throughout the winter. The
recommended daily allowance (RDA) for vitamin D is 400 IU for people aged 51 to 70 and 
600 IU for
those >70; many consider this intake too low, and the 2005 Dietary Guidelines for Americans
recommends that healthy older adults consume 1000 IU/day. Vitamin D Toxicity
Usually, vitamin D toxicity results from taking excessive amounts.


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Marked hypercalcemia
commonly causes symptoms. Diagnosis is typically based on elevated blood levels of 25(OH)D. Treatment consists of stopping vitamin D, restricting dietary Ca, restoring intravascular volume
deficits, and, if toxicity is severe, giving corticosteroids or bisphosphonates. Because synthesis of 1,25(OH)
2
D (the most active metabolite of vitamin D) is tightly regulated, vitamin D
toxicity usually occurs only if excessive doses (prescription or megavitamin) are taken. Vitamin D 1000 
μ
g
(40,000 IU)/day causes toxicity within 1 to 4 mo in infants. In adults, taking 1250 
μ
g (50,000 IU)/day for
several months can cause toxicity. Vitamin D toxicity can occur iatrogenically when hypoparathyroidism is
treated too aggressively (see p.


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Symptoms and Signs
The main symptoms result from hypercalcemia. Anorexia, nausea, and vomiting can develop, often
followed by polyuria, polydipsia, weakness, nervousness, pruritus, and eventually renal failure. Proteinuria, urinary casts, azotemia, and metastatic calcifications (particularly in the kidneys) can develop. Diagnosis
• Hypercalcemia plus risk factors or elevated serum 25(OH)D levels
A history of excessive vitamin D intake may be the only clue differentiating vitamin D toxicity from other
causes of hypercalcemia. Elevated serum Ca levels of 12 to 16 mg/dL (3 to 4 mmol/L) are a constant
finding when toxic symptoms occur. Serum 25(OH)D levels are usually elevated > 150 ng/mL (> 375
nmol/L). Levels of 1,25(OH)
2
D, which need not be measured to confirm the diagnosis, may be normal. Serum Ca should be measured often (weekly at first, then monthly) in all patients receiving large doses of
vitamin D, particularly the potent 1,25(OH)
2
D. Treatment
• IV hydration plus corticosteroids or bisphosphonates
After stopping vitamin D intake, hydration with IV normal saline and corticosteroids or bisphosphonates
(which inhibit bone resorption) are used to reduce blood Ca levels. Kidney damage or metastatic calcifications, if present, may be irreversible.


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Vitamin E
Vitamin E is a group of compounds (including tocopherols and tocotrienols) that have similar biologic
activities.


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The most biologically active is 
α
-tocopherol, but 
β
-, 
γ
-, and 
δ
-tocopherols, 4 tocotrienols, and
several stereoisomers may also have important biologic activity. These compounds act as antioxidants,
which prevent lipid peroxidation of polyunsaturated fatty acids in cellular membranes. Plasma tocopherol
levels vary with total plasma lipid levels. Normally, the plasma 
α
-tocopherol level is 5 to 20 
μ
g/mL (11.6 to
46.4 
μ
mol/L). High-dose vitamin E supplements do not protect against cardiovascular disorders;whether
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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supplements can protect against Alzheimer's disease, tardive dyskinesia, and prostate cancer among
smokers is controversial. Although the amount of vitamin E in many fortified foods and supplements is given in IU, current
recommendations are to use mg. Vitamin E Deficiency
Dietary vitamin E deficiency is common in developing countries; deficiency among adults in
developed countries is uncommon and usually due to fat malabsorption. The main symptoms
are hemolytic anemia and neurologic deficits. Diagnosis is based on measuring the ratio of
plasma 
α
-tocopherol to total plasma lipids; a low ratio suggests vitamin E deficiency. Treatment
consists of oral vitamin E, given in high doses if there are neurologic deficits or if deficiency
results from malabsorption. Vitamin E deficiency causes fragility of RBCs and degeneration of neurons, particularly peripheral axons
and posterior column neurons. Etiology
In developing countries, the most common cause is inadequate intake of vitamin E.


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In developed
countries, the most common causes are disorders that cause fat malabsorption, including
abetalipoproteinemia (Bassen-Kornzweig syndrome, due to genetic absence of apolipoprotein B), chronic
cholestatic 
hepatobiliary disease, pancreatitis, short bowel syndrome, and cystic fibrosis. A rare genetic
form of vitamin E deficiency without fat malabsorption results from defective liver metabolism. Symptoms and Signs
The main symptoms are mild hemolytic anemia and nonspecific neurologic deficits. Abetalipoproteinemia
results in progressive neuropathy and retinopathy in the first 2 decades of life (see p.


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904
). Vitamin E deficiency may contribute to retinopathy of prematurity (also called retrolental fibroplasia) in
premature infants and to some cases of intraventricular and subependymal hemorrhage in neonates. Affected premature neonates have muscle weakness. In children, chronic cholestatic hepatobiliary disease or cystic fibrosis causes neurologic deficits, including
spinocerebellar ataxia with loss of deep tendon reflexes, truncal and limb ataxia, loss of vibration and
position senses, ophthalmoplegia, muscle weakness, ptosis, and dysarthria. In adults with malabsorption, vitamin E deficiency very rarely causes spinocerebellar ataxia because
adults have large vitamin E stores in adipose tissue. Diagnosis
• Low 
α
-tocopherol level or low ratio of serum 
α
-tocopherol to serum lipids
Without a history of inadequate intake or a predisposing condition, vitamin E deficiency is unlikely.


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Measuring RBC hemolysis in response to
peroxide can suggest the diagnosis but is nonspecific. Hemolysis increases as vitamin E deficiency
impairs RBC stability. Measuring the serum 
α
-tocopherol level is the most direct method of diagnosis. In adults, vitamin E
deficiency is suggested if the 
α
-tocopherol level is < 5 
μ
g/mL (< 11.6 
μ
mol/L). Because abnormal lipid
levels can affect vitamin E status, a low ratio of serum 
α
-tocopherol to lipids (< 0.8 mg/g total lipid) is the
most accurate indicator in adults with hyperlipidemia. In children and adults with abetalipoproteinemia, serum 
α
-tocopherol levels are usually undetectable. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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Treatment
• Supplemental 
α
-tocopherol
If malabsorption causes clinically evident deficiency, 
α
-tocopherol 15 to 25 mg/kg po once/day should be
given. However, larger doses given by injection are required to treat neuropathy during its early stages or
to overcome the defect of absorption and transport in abetalipoproteinemia. Prevention
Although premature neonates may require supplementation, human milk and commercial formulas have
enough vitamin E for full-term neonates. Vitamin E Toxicity
Many adults take relatively large amounts of vitamin E (
α
-tocopherol 400 to 800 mg/day) for months to
years without any apparent harm. Occasionally, muscle weakness, fatigue, nausea, and diarrhea occur.


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However, bleeding is uncommon unless the dose is > 1000 mg/day
or the patient takes oral coumarin or warfarin. Thus, the upper limit for adults aged ≥19 yr is 1000 mg for
any form of 
α
-tocopherol. Recent analyses of previous studies report that high vitamin E intakes may
increase the risk of hemorrhagic stroke and premature death.


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Dietary fat enhances its absorption. Infant formulas
contain supplemental vitamin K. Vitamin K
2
 refers to a group of compounds (menaquinones) synthesized
by bacteria in the intestinal tract; the amount synthesized does not satisfy the vitamin K requirement. Vitamin K controls the formation of coagulation factors II (prothrombin), VII, IX, and X in the liver. Other
coagulation factors dependent on vitamin K are protein C, protein S, and protein Z; proteins C and S are
anticoagulants. Metabolic pathways conserve vitamin K. Once vitamin K has participated in formation of
coagulation factors, the reaction product, vitamin K epoxide, is enzymatically converted to the active form,
vitamin K hydroquinone. The actions of vitamin K-dependent proteins require Ca. The vitamin K-dependent proteins, osteocalcin
and matrix 
γ
-carboxy-glutamyl (Gla) protein, may have important roles in bone and other tissues. Forms of
vitamin K are common therapy for osteoporosis in Japan and other countries. Vitamin K Deficiency
Vitamin K deficiency results from extremely inadequate intake, fat malabsorption, or use of
coumarin anticoagulants. Deficiency is particularly common among breastfed infants. It impairs
clotting.


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Diagnosis is suspected based on routine coagulation study findings and confirmed by
response to vitamin K. Treatment consists of vitamin K given orally or, when fat malabsorption
is the cause or risk of bleeding is high, parenterally. Vitamin K deficiency decreases levels of prothrombin and other vitamin K-dependent coagulation factors,
causing defective coagulation and, potentially, bleeding. Etiology
Worldwide, vitamin K deficiency causes infant morbidity and mortality. Vitamin K deficiency causes
hemorrhagic disease of the newborn, which usually occurs 1 to 7 days postpartum. In affected neonates,
birth trauma can cause intracranial hemorrhage. Neonates are prone to vitamin K deficiency because of
the following:
• The placenta transmits lipids and vitamin K relatively poorly. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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• The neonatal liver is immature with respect to prothrombin synthesis. • Breast milk is low in vitamin K, containing about 2.5 
μ
g/L (cow's milk contains 5000 
μ
g/L). • The neonatal gut is sterile during the first few days of life. Late hemorrhagic disease (occurring 3 to 8 wk postpartum) is usually associated with breastfeeding,
malabsorption, or a liver disorder. If the mother has taken phenytoin anticonvulsants, coumarin
anticoagulants, or cephalosporin antibiotics, the risk of both types of hemorrhagic disease is increased. In healthy adults, dietary vitamin K deficiency is uncommon because vitamin K is widely distributed in
green vegetables and the bacteria of the normal gut synthesize menaquinones. However, biliary
obstruction, malabsorption, cystic fibrosis, and resection of the small intestine can contribute to vitamin K
deficiency. Coumarin anticoagulants interfere with the synthesis of vitamin K-dependent coagulation proteins (factors
II, VII, IX, and X) in the liver. Certain antibiotics (particularly some cephalosporins and other broad-
spectrum antibiotics), salicylates, megadoses of vitamin E, and hepatic insufficiency increase risk of
bleeding in patients with vitamin K deficiency. Symptoms and Signs
Bleeding is the usual manifestation.


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Easy bruisability and mucosal bleeding (especially epistaxis, GI
hemorrhage, menorrhagia, and hematuria) can occur. Blood may ooze from puncture sites or incisions. Hemorrhagic disease of the newborn and late hemorrhagic disease in infants may cause cutaneous, GI,
intrathoracic, or, in the worst cases, intracranial bleeding. If obstructive jaundice develops, bleeding—if it
occurs—usually begins after the 4th or 5th day.


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It may begin as a slow ooze from a surgical incision, the
gums, the nose, or GI mucosa, or it may begin as massive bleeding into the GI tract. Diagnosis
• Usually, prolonged PT that decreases after phytonadione
Vitamin K deficiency or antagonism (due to coumarin anticoagulants) is suspected when abnormal
bleeding occurs in a patient at risk. Blood coagulation studies can preliminarily confirm the diagnosis. PT,
usually reported as the INR, is prolonged, but PTT, thrombin time, platelet count, bleeding time, and
levels of fibrinogen, fibrin-split products, and D-dimer are normal. If phytonadione (USP generic name for
vitamin K
1
) 1 mg IV significantly decreases PT within 2 to 6 h, a liver disorder is not the likely cause, and
the diagnosis of vitamin K deficiency is confirmed. Some centers can detect vitamin K deficiency more
directly by measuring the serum vitamin level.


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The serum level of vitamin K
1
 ranges from 0.2 to 1.0 ng/mL
in healthy people consuming adequate quantities of vitamin K
1
 (50 to 150 
μ
g/day). Knowing vitamin K
intake can help interpret serum levels; recent intake affects levels in serum but not in tissues.


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More sensitive indicators of vitamin K status, such as PIVKA (
P
rotein 
I
nduced in 
V
itamin 
K A
bsence or
A
ntagonism) and under-carboxylated osteocalcin, are under study. Treatment
• Phytonadione
Whenever possible, phytonadione should be given po or sc.


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The usual adult dose is 5 to 20 mg. (Rarely,
even when phytonadione is correctly diluted and given slowly, IV replacement can result in anaphylaxis or
anaphylactoid reactions.) INR usually decreases within 6 to 12 h. The dose may be repeated in 6 to 8 h if
INR has not decreased satisfactorily. Phytonadione 2.5 to 10 mg po is indicated for 
nonemergency
correction of a prolonged INR in patients taking anticoagulants. Correction usually occurs within 6 to 8 h.


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When only partial correction of INR is desirable (eg, when INR should remain slightly elevated because of
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity
97


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a prosthetic heart valve), lower doses (eg, 1 to 2.5 mg) of phytonadione can be given. In infants, bleeding due to deficiency can be corrected by giving phytonadione 1 mg sc or IM once. The
dose is repeated if INR remains elevated. Higher doses may be necessary if the mother has been taking
oral anticoagulants. Prevention
Phytonadione 0.5 to 1 mg IM (or 0.3 mg/kg for preterm infants) is recommended for all neonates within 6 h
of birth to reduce the incidence of intracranial hemorrhage due to birth trauma and of classic hemorrhagic
disease of the newborn (increased bleeding risks 1 to 7 days after birth). It is also used prophylactically
before surgery. Some clinicians recommend that pregnant women taking anticonvulsants receive
phytonadione 10 mg po once/day for the 1 mo or 20 mg po once/day for the 2 wk before delivery. The low
vitamin K
1
 content in breast milk can be increased by increasing maternal dietary intake of phylloquinone
to 5 mg/day. Vitamin K Toxicity
Vitamin K
1
 (phylloquinone) is not toxic when consumed orally, even in large amounts.


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However,
menadione (a synthetic, water-soluble vitamin K precursor) can cause toxicity and should not be used to
treat vitamin K deficiency. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4.


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Chapter 5. Mineral Deficiency and Toxicity
Introduction
Six macrominerals are required by people in gram amounts. Four (Na, K, Ca, and Mg) are cations; two (Cl
and P) are accompanying anions (see p.


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Daily requirements range from 0.3 to 2.0 g. Bone, muscle,
heart, and brain function depend on these minerals. Nine trace minerals (microminerals) are required by people in minute amounts: chromium, copper, iodine,
iron, fluorine, manganese, molybdenum, selenium, and zinc. (For sources, functions, effects of deficiency
and toxicity, and dietary requirements, see
Tables 5-1
 and
5-2
.) All trace minerals are toxic at high levels; some minerals (arsenic, nickel, and chromium) may be
carcinogens. Mineral deficiencies (except of iodine, iron, and zinc) do not often develop spontaneously in adults on
ordinary diets; infants are more vulnerable because their growth is rapid and intake varies. Trace mineral
imbalances can result from hereditary disorders (eg, hemochromatosis, Wilson's disease), kidney dialysis,
parenteral nutrition, or restrictive diets prescribed for people with inborn errors of metabolism. Chromium
Only 1 to 3% of biologically active trivalent chromium (Cr) is absorbed. Normal plasma levels are 0.05 to
0.50 
μ
g/L (1.0 to 9.6 nmol/L). Chromium potentiates insulin activity and increases the growth rate in
undernourished children.


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Supplements do not enhance muscle size or strength in men. Deficiency:
 Four patients receiving long-term TPN developed possible chromium deficiency, with
glucose intolerance, weight loss, ataxia, and peripheral neuropathy. Symptoms resolved in 3 who were
given trivalent chromium 150 to 250 mg.


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Toxicity:
 High doses of trivalent chromium given parenterally cause skin irritation, but lower doses given
orally are not toxic. Exposure to hexavalent chromium (CrO
3
) in the workplace may irritate the skin, lungs,
and GI tract and may cause perforation of the nasal septum and lung carcinoma. Copper
Copper is a component of many body proteins; almost all of the body's copper is bound to copper
proteins.


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Unbound (free) copper ions are toxic. Genetic mechanisms control the incorporation of copper
into apoproteins and the processes that prevent toxic accumulation of copper in the body. Copper
absorbed in excess of metabolic requirements is excreted through bile. [
Table 5-1. Trace Minerals]
Acquired Copper Deficiency
If the genetic mechanisms controlling copper metabolism are normal, dietary deficiency rarely causes
clinically significant copper deficiency. The only reported causes are kwashiorkor, persistent infantile
diarrhea (usually associated with a diet limited to milk), severe malabsorption (as in sprue), and excessive
zinc intake. Deficiency may cause neutropenia, impaired bone calcification, and hypochromic anemia not responsive
to iron supplements. Diagnosis is based on low serum levels of copper and ceruloplasmin, although these tests are not always
reliable. Treatment is directed at the cause, and copper 1.5 to 3 mg/day po (usually as copper sulfate) is
given. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5.


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Inherited Copper Deficiency
(Menkes Syndrome)
Inherited copper deficiency occurs in male infants who inherit a mutant X-linked gene. Incidence is about
1 in 50,000 live births. Copper is deficient in the liver, serum, and essential copper proteins, including
cytochrome-c oxidase, ceruloplasmin, and lysyl oxidase. Symptoms are severe intellectual disability, vomiting, diarrhea, protein-losing enteropathy,
hypopigmentation, bone changes, and arterial rupture; the hair is sparse, steely, or kinky. Diagnosis
• Serum copper and ceruloplasmin levels
• Serum levels of dopamine, norepinephrine, dihydroxyphenylacetic acid, and dihydroxyphenylglycol in
infants at risk
Diagnosis is based on low copper and ceruloplasmin levels in serum, although these tests are not always
reliable. Because early diagnosis and treatment seem to result in a better prognosis, the disorder is
ideally detected before age 2 wk.


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However, diagnostic accuracy of these tests is limited. Thus, infants at
risk (eg, those with a family history) can be screened by measuring dopamine, norepinephrine,
dihydroxyphenylacetic acid, and dihydroxyphenylglycol in serum. A dihydroxyphenylacetic
acid:dihydroxyphenylglycol ratio of > 4 seems to indicate deficiency, and a dopamine:norepinephrine ratio
of > 0.2 seems to confirm it. Treatment
• Copper histidine
Parenteral copper is usually given as copper histidine 250 
μ
g sc bid to age 1 yr, then 250 
μ
g sc once/day
until age 3 yr; monitoring kidney function is essential during treatment. Despite early treatment, many
children have abnormal neurodevelopment.


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Acquired Copper Toxicity
Acquired copper toxicity can result from ingesting or absorbing excess copper (eg, from ingesting an
acidic food or beverage that has had prolonged contact with a copper container). Self-limited
gastroenteritis with nausea, vomiting, and diarrhea may occur. [
Table 5-2. Guidelines for Daily Intake of Minerals]
More severe toxicity results from ingestion (usually with suicidal intent) of gram quantities of a copper salt
(eg, copper sulfate) or from absorption of large amounts through the skin (eg, if compresses saturated
with a solution of a copper salt are applied to large areas of burned skin). Hemolytic anemia and anuria
can result and may be fatal. Indian childhood cirrhosis, non-Indian childhood cirrhosis, and idiopathic copper toxicity are probably
identical disorders in which excess copper causes cirrhosis. All seem to be caused by ingesting milk that
has been boiled or stored in corroded copper or brass vessels. Recent studies suggest that idiopathic
copper toxicity may develop only in infants with an unknown genetic defect. Diagnosis usually requires liver biopsy, which shows Mallory hyalin bodies.


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• Supportive measures
For copper toxicity due to ingesting grams of copper, prompt gastric lavage is done. Copper toxicity that
causes complications such as hemolytic anemia, anuria, or hepatotoxicity is also treated with either oral
penicillamine 250 mg q 6 h to 750 mg q 12 h (1000 to 1500 mg/day in 2 to 4 doses) or dimercaprol 3 to 5
mg/kg IM q 4 h for 2 days, then q 4 to 6 h (see also
Table 340-4
 and copper salts in
Table 340-8
). If used early, hemodialysis may be effective.


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Occasionally, copper toxicity is fatal despite
treatment. Inherited Copper Toxicity
(Wilson's Disease)
Inherited copper toxicity results in accumulation of copper in the liver and other organs. Hepatic
or neurologic symptoms develop.


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Diagnosis is based on a low serum ceruloplasmin level, high
urinary excretion of copper, and sometimes liver biopsy results. Treatment consists of a low-
copper diet and chelation, usually with penicillamine or dimercaprol. Wilson's disease is a progressive disorder of copper metabolism that affects 1 person in 30,000. Affected
people are homozygous for the mutant recessive gene, located on chromosome 13.


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Heterozygous
carriers, who constitute about 1.1% of the population, are asymptomatic. Pathophysiology
The genetic defect impairs copper transport. The impaired transport decreases copper secretion into the
bile, thus causing the copper overload and resultant accumulation in the liver, which begins at birth. The
impaired transport also interferes with incorporation of copper into the copper protein ceruloplasmin, thus
decreasing serum levels of ceruloplasmin. Hepatic fibrosis develops, ultimately causing cirrhosis. Copper diffuses out of the liver into the blood, then
into other tissues. It is most destructive to the brain but also damages the kidneys and reproductive
organs and causes hemolytic anemia. Some copper is deposited in Descemet's membrane of the cornea,
causing Kayser-Fleischer rings. Symptoms and Signs
Symptoms usually develop between ages 5 and 40.


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In almost half of patients, particularly adolescents,
the first symptom is hepatitis—acute, chronic active, or fulminant. But hepatitis may develop at any time. In about 40% of patients, particularly young adults, the first symptoms reflect CNS involvement. Motor
deficits are common, including any combination of tremors, dystonia, dysarthria, dysphagia, chorea,
drooling, and incoordination. Sometimes the first symptoms are cognitive or psychiatric abnormalities.


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In 5
to 10% of patients, the first symptom is incidentally noted gold or greenish gold Kayser-Fleischer rings or
crescents (due to copper deposits in the cornea), amenorrhea or repeated miscarriages, or hematuria. Diagnosis
• Slit-lamp examination for Kayser-Fleischer rings
• Serum ceruloplasmin and 24-h urinary copper excretion
• Sometimes confirmation by penicillamine provocation test or liver biopsy
Wilson's disease should be suspected in people < 40 with any of the following:
• An unexplained hepatic, neurologic, or psychiatric disorder
• An unexplained persistent elevation in hepatic transaminases
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity
101


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• A sibling, parent, or cousin with Wilson's disease
• Fulminant hepatitis
If Wilson's disease is suspected, slit-lamp examination for Kayser-Fleischer rings is required, and serum
ceruloplasmin and copper levels and 24-h urinary copper excretion are measured. Transaminase levels
are also often measured; high levels are consistent with the diagnosis. Kayser-Fleischer rings:
 These rings plus typical motor neurologic abnormalities or a decrease in
ceruloplasmin are nearly pathognomonic for Wilson's disease. Rarely, these rings occur in other liver
disorders (eg, biliary atresia, primary biliary cirrhosis), but ceruloplasmin levels should be unaffected. Ceruloplasmin:
 Serum ceruloplasmin (normally 20 to 35 mg/dL) is usually low in Wilson's disease but
can be normal. It can also be low in heterozygous carriers and those with other liver disorders (eg, viral
hepatitis, drug- or alcohol-induced liver disease). A low ceruloplasmin level in a patient with a 
Kayser-
Fleischer ring is diagnostic. Also, a level of < 5 mg/dL is highly suggestive regardless of clinical findings.


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Serum copper:
 Despite the copper accumulation in the body, serum copper levels are decreased
because of the decreased ceruloplasmin levels. Urinary copper excretion:
 In Wilson's disease, 24-h urinary copper excretion (normally, ≤ 30 
μ
g/day) is
usually > 100 
μ
g/day. If serum ceruloplasmin is low and urinary copper excretion is high, diagnosis is
clear. If levels are equivocal, measuring urinary copper excretion after penicillamine is given
(penicillamine provocation test) may confirm the diagnosis; this test is not usually done in adults because
cutoff values are not well-established. Liver biopsy:
 In unclear cases (eg, elevated transaminases, no Kayser-Fleischer rings, indeterminate
values for ceruloplasmin and urinary copper), the diagnosis is made by doing a liver biopsy to measure
hepatic copper concentration. However, false-negative results may occur because of a sampling error
(due to large variations in copper concentrations in the liver) or fulminant hepatitis (causing necrosis that
releases large amounts of copper). Screening:
 Because early treatment is most effective, screening is indicated for anyone who has a
sibling, cousin, or parent with Wilson's disease. Screening consists of a slit-lamp examination and
measurement of transaminase levels, serum copper and ceruloplasmin, and 24-h urine copper excretion.


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If any results are abnormal, liver biopsy is done to measure hepatic copper concentration. Infants should
not be tested until after age 1 yr because ceruloplasmin levels are low during the first few months of life. Children < 6 yr with normal test results should be retested 5 to 10 yr later.


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Untreated Wilson's
disease is fatal, usually by age 30. Treatment
• Penicillamine or another chelating drug if needed to remove accumulated copper
• Low-copper diet
• For maintenance, lifelong low-dose chelation therapy or oral zinc
Continual, lifelong treatment is mandatory regardless of whether symptoms are present. Accumulated
copper should be removed with chelating drugs. A low-copper diet (eg, avoiding beef liver, cashews,
black-eyed peas, vegetable juice, shellfish, mushrooms, and cocoa) and use of either low-dose chelation
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity
102


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therapy or oral zinc can prevent copper from accumulating. Penicillamine is the most commonly used chelating drug but has considerable toxicity (eg, fever, rash,
neutropenia, thrombocytopenia, proteinuria). Cross-reactivity may occur in people with penicillin allergy.


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Patients > 5 yr are given oral doses of 62.5 mg q 6 h to 250 mg q 12 h (250 to 500 mg/day in 2 to 4
doses) and slowly increased to a maximum of 250 mg q 6 h to 750 mg q 12 h (1000 to 1500 mg/day in 2
to 4 doses).


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Younger children are given 10 mg/kg bid or 6.7 mg/kg tid (20 mg/kg/d) po. Pyridoxine 25 mg
po once/day is given with penicillamine. Occasionally, use of penicillamine is associated with worsening
neurologic symptoms. Trientine hydrochloride is an alternative treatment to penicillamine. Doses are 375 to 750 mg po bid or
250 to 500 mg po tid (750 to 1500 mg/day). Zinc acetate 50 mg po tid can prevent reaccumulation of copper in patients who cannot tolerate
penicillamine or trientine or who have neurologic symptoms that do not respond to the other drugs. (CAUTION: 
Penicillamine or trientine must not be given with zinc because either drug can bind zinc,
forming a compound with no therapeutic effect
.)
Poor long-term adherence to drug therapy is common. After 1 to 5 yr of therapy, lower dose maintenance
drug therapy can be considered.


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Regular follow-up care with an expert in liver disease is recommended. Liver transplantation may be lifesaving for patients who have Wilson's disease and fulminant hepatic
failure or severe hepatic insufficiency refractory to drugs. Fluorine
Most of the body's fluorine (F) is contained in bones and teeth.


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Fluoride (the ionic form of fluorine) is
widely distributed in nature. The main source of fluoride is fluoridated drinking water. Deficiency:
 Fluorine deficiency can lead to dental caries and possibly osteoporosis. Fluoridation of
water that contains < 1 ppm (the ideal) reduces the incidence of dental caries. If a child's drinking water is
not fluoridated, oral fluoride supplements can be prescribed. Toxicity:
 Excess fluorine can accumulate in teeth and bones, causing fluorosis. Drinking water
containing > 10 ppm is a common cause. Permanent teeth that develop during 
high fluoride intake are
most likely to be affected.


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Exposure must be much greater to affect deciduous teeth. The earliest signs are chalky white, irregularly distributed patches on the surface of the enamel; these
patches become stained yellow or brown, producing a characteristic mottled appearance. Severe toxicity
weakens the enamel, pitting its surface. Bony changes, including osteosclerosis, exostoses of the spine,
and genu valgum, can develop but only in adults after prolonged high intake of fluoride. No tests to diagnose toxicity are available.


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Treatment involves reducing fluoride intake; eg, in areas with high fluoride water levels, patients should
not drink fluoridated water or take fluoride supplements. Children should always be told not to swallow
fluoridated toothpastes. Iodine
In the body, iodine (I) is involved primarily in the synthesis of 2 thyroid hormones, thyroxine (T
4
) and
triiodothyronine (T
3
). Iodine occurs in the environment and in the diet primarily as iodide. In adults, about
80% of the iodide absorbed is trapped by the thyroid gland. Most environmental iodine occurs in
seawater as iodide; a small amount enters the atmosphere and, through rain, enters ground water and
soil near the sea. Thus, people living far from the sea and at higher altitudes are at particular risk of
deficiency. Fortifying table salt with iodide (typically 70 
μ
g/g) helps ensure adequate intake (150 
μ
g/day). Requirements are higher for pregnant (220 
μ
g/day) and breastfeeding (290 
μ
g/day) women.


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Iodine Deficiency
Deficiency is rare in areas where iodized salt is used but common worldwide. Iodine deficiency develops
when iodide intake is < 20 
μ
g/day. In mild or moderate deficiency, the thyroid gland, influenced by thyroid-
stimulating hormone (TSH), hypertrophies to concentrate iodide in itself, resulting in colloid goiter. Usually, patients remain euthyroid; however, severe iodine deficiency in adults may cause hypothyroidism
(endemic myxedema). It can decrease fertility and increase risk of stillbirth, spontaneous abortion, and
prenatal and infant mortality. Severe maternal iodine deficiency retards fetal growth and brain
development, sometimes resulting in birth defects, and, in infants, causes cretinism, which may include
intellectual disability, deaf-mutism, difficulty walking, short stature, and sometimes hypothyroidism. Diagnosis
• Assessment of thyroid structure and function
Diagnosis in adults and children is usually based on thyroid function, examination for goiter, and imaging
tests identifying abnormalities in thyroid function and structure (see p.


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All neonates should be screened by measuring the TSH level. Treatment
• Iodide with or without levothyroxine
Infants with iodine deficiency are given L-thyroxine 3 
μ
g/kg po once/day for a week plus iodide 50 to 90
μ
g po once/day for several weeks to quickly restore a euthyroid state. Children are treated with iodide 90
to 120 
μ
g once/day. Adults are given iodide 150 
μ
g once/day. Iodine deficiency can also be treated by
giving levothyroxine. Serum TSH levels are monitored in all patients until the levels are normal (ie, < 5
μ
IU/mL). Iodine Toxicity
Chronic toxicity may develop when intake is > 1.1 mg/day. Most people who ingest excess amounts of
iodine remain euthyroid. Some people who ingest excess amounts of iodine, particularly those who were
previously deficient, develop hyperthyroidism (Jod-Basedow phenomenon). Paradoxically, excess uptake
of iodine by the thyroid may inhibit thyroid hormone synthesis (called Wolff-Chaikoff effect). Thus, iodine
toxicity can eventually cause iodide goiter, hypothyroidism, or myxedema. Very large amounts of iodide
may cause a brassy taste in the mouth, increased salivation, GI irritation, and acneiform skin lesions. Patients exposed to frequent large amounts of radiographic contrast dyes or the drug amiodarone also
need to have their thyroid function monitored.


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776
), which are
correlated with clinical data. Iodine excretion may be more specific but is not usually measured.


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Treatment
consists of correcting thyroid abnormalities and, if intake is excessive, dietary modification. Iron
Iron (Fe) is a component of hemoglobin, myoglobin, and many enzymes in the body.


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Heme iron, contained
mainly in animal products, is absorbed much better than nonheme iron (eg, in plants and grains), which
accounts for > 85% of iron in the average diet. However, absorption of nonheme iron is increased when it
is consumed with animal protein and vitamin C. Deficiency:
 Iron deficiency is one of the most common mineral deficiencies in the world. It may result
from the following:
• Inadequate iron intake, common in infants, adolescent girls, and pregnant women
• Malabsorption (eg, celiac sprue)
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity
104


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• Chronic bleeding
Chronic bleeding due to colon cancer is a serious cause in middle-aged people and the elderly. When deficiency is advanced, microcytic anemia develops (see p.


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924
). In addition to anemia, iron deficiency may cause pica (a craving for nonfoods) and spoon nails and is
associated with restless leg syndrome. Rarely, iron deficiency causes dysphagia due to postcricoid
esophageal web. Diagnosis involves CBC, serum ferritin, and possibly measurement of transferrin saturation (iron
capacity).


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All people with moderate or severe iron deficiency and some people with mild deficiency require iron
supplementation. Toxicity:
 Iron may accumulate in the body because of
• Iron therapy given in excessive amounts or for too long
• Repeated blood transfusions
• Chronic alcoholism
• Overdose of iron
Iron overload can also result from an inherited iron overload disease (hemochromatosis—see p. 1032
), a
potentially fatal but easily treatable genetic disorder in which too much iron is absorbed. Hemochromatosis affects > 1 million Americans. An overdose of iron is toxic (see p. 3341
), causing vomiting, diarrhea, and damage to the intestine and
other organs. Diagnosis is similar to that for iron deficiency.


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Treatment often involves deferoxamine, which binds with iron and is excreted in urine. Manganese
Manganese (Mn), necessary for healthy bone structure, is a component of several enzyme systems,
including manganese-specific glycosyltransferases and phosphoenolpyruvate carboxykinase. Median
intake is between 1.6 and 2.3 mg/day; absorption is 5 to 10%.


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Deficiency has not been conclusively documented, although one experimental case in a volunteer
resulted in transient dermatitis, hypocholesterolemia, and increased alkaline phosphatase levels. Toxicity is usually limited to people who mine and refine ore; prolonged exposure causes neurologic
symptoms resembling those of parkinsonism or Wilson's disease. Molybdenum
Molybdenum (Mo) is a component of coenzymes necessary for the activity of xanthine oxidase, sulfite
oxidase, and aldehyde oxidase. Genetic and nutritional deficiencies of molybdenum have been reported but are rare. Genetic sulfite
oxidase deficiency was described in 1967 in a child. It resulted from the inability to form the molybdenum
coenzyme despite the presence of adequate molybdenum. The deficiency caused intellectual disability,
seizures, opisthotonus, and lens dislocation. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5.


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Molybdenum deficiency resulting in sulfite toxicity occurred in a patient receiving long-term TPN. Symptoms were tachycardia, tachypnea, headache, nausea, vomiting, and coma. Laboratory tests
showed high levels of sulfite and xanthine and low levels of sulfate and uric acid in the blood and urine. Ammonium molybdate 300 
μ
g/day IV caused dramatic recovery. A case of molybdenum toxicity may have occurred in 1961; it caused goutlike symptoms and
abnormalities of the GI tract, liver, and kidneys. Selenium
Selenium (Se) is a part of the enzyme glutathione peroxidase, which metabolizes hydro-peroxides formed
from polyunsaturated fatty acids.


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Selenium is also a part of the enzymes that deiodinate thyroid
hormones. Generally, selenium acts as an antioxidant that works with vitamin E. Some epidemiologic
studies associate low selenium levels with cancer. In children with Down syndrome, selenium
supplements may help prevent bacterial infections. Plasma levels vary from 8 to 25 
μ
g/dL, depending on
selenium intake.


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Diagnosis is usually clinical; sometimes blood glutathione peroxidase is measured. Deficiency:
 Deficiency is rare, even in New Zealand and Finland, where selenium intake 
is 30 to 50
μ
g/day, compared with 100 to 250 
μ
g/day in the US and Canada. In certain areas of China, where intake
averages 10 to 15 
μ
g/day, selenium deficiency predisposes patients to Keshan disease, an endemic viral
cardiomyopathy affecting primarily children and young women. This cardiomyopathy can be prevented
but not cured by sodium selenite supplements of 50 
μ
g/day po. Patients receiving long-term TPN have
developed selenium deficiency with muscle pain and tenderness that responded to a selenomethionine
supplement. In Siberian Russia and China, growing children with selenium deficiency may develop
chronic osteoarthropathy (Kashin-Beck disease).


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Selenium deficiency may contribute synergistically with
iodine deficiency to the development of goiter and hypothyroidism. Diagnosis is made clinically or sometimes by measuring glutathione peroxidase activity or plasma
selenium, but neither of these tests is readily available.


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Treatment consists of sodium selenite 100 
μ
g/day
po. Toxicity:
 At high doses (> 900 
μ
g/day), selenium causes toxicity. Manifestations include hair loss,
abnormal nails, dermatitis, peripheral neuropathy, nausea, diarrhea, fatigue, irritability, and a garlic odor of
the breath. Toxic levels of plasma selenium are not well defined. Zinc
Zinc (Zn) is contained mainly in bones, teeth, hair, skin, liver, muscle, leukocytes, and testes. Zinc is a
component of several hundred enzymes, including many nicotinamide adenine dinucleotide (NADH)
dehydrogenases, RNA and DNA polymerases, and DNA transcription factors as well as alkaline
phosphatase, superoxide dismutase, and carbonic anhydrase. A diet high in fiber and phytate (eg, in
whole-grain bread) reduces zinc absorption.


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Deficiency:
 Dietary deficiency is unlikely in healthy people. Secondary zinc deficiency can develop in the
following:
• Some patients with hepatic insufficiency (because the ability to retain zinc is lost)
• Patients taking diuretics
• Patients with diabetes mellitus, sickle cell disease, chronic renal failure, or malabsorption
• Patients with stressful conditions (eg, sepsis, burns, head injury)
• Elderly institutionalized and homebound patients (common)
Maternal zinc deficiency may cause fetal malformations and low birth weight. The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5.


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Zinc deficiency in children causes impaired growth and impaired taste (hypogeusia). Other symptoms and
signs in children include delayed sexual maturation and hypogonadism. In children or adults, symptoms
include hypogonadism, alopecia, impaired immunity, anorexia, dermatitis, night blindness, anemia,
lethargy, and impaired wound healing. Zinc deficiency should be suspected in undernourished patients with typical symptoms or signs. However,
because many of the symptoms and signs are nonspecific, clinical diagnosis of mild zinc deficiency is
difficult. Laboratory diagnosis is also difficult. Low albumin levels, common in zinc deficiency, make serum
zinc levels difficult to interpret; diagnosis usually requires the combination of low levels of zinc in serum
and increased urinary zinc excretion. If available, isotope studies can measure zinc status more
accurately.


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Treatment consists of elemental zinc 15 to 120 mg/day po until symptoms and signs resolve. Acrodermatitis enteropathica
 (a rare, once fatal autosomal recessive disorder) causes malabsorption
of zinc. Psoriasiform dermatitis develops around the eyes, nose, and mouth; on the buttocks; and in an
acral distribution. The disorder also causes hair loss, paronychia, impaired immunity, recurrent infection,
impaired growth, and diarrhea.


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In such cases, doctors suspect the diagnosis. If deficiency is diagnosed, zinc sulfate 30 to 150
mg/day po usually results in complete remission. Toxicity:
 The recommended upper limit for zinc intake is 40 mg/day. Toxicity is rare. Ingesting doses of
elemental zinc ranging from 100 to 150 mg/day for prolonged periods interferes with copper metabolism
and causes low blood copper levels, RBC microcytosis, neutropenia, and impaired immunity; higher
doses should be given only for short periods of time and the patient should be followed closely. Ingesting
larger amounts (200 to 800 mg/day), usually by consuming acidic food or drink from a galvanized (zinc-
coated) container, can cause anorexia, vomiting, and diarrhea. Metal fume fever, also called brass-
founders' ague or zinc shakes, is caused by inhaling industrial zinc oxide fumes; it results in neurologic
damage. Symptoms usually resolve after 12 to 24 h in a zinc-free environment.


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Chapter 6. Obesity and the Metabolic Syndrome
Obesity
Obesity is excess body fat; consequences depend not only on the absolute amount but also on
the distribution of the fat. Complications include cardiovascular disorders, diabetes mellitus,
many cancers, cholelithiasis, fatty liver and cirrhosis, osteoarthritis, reproductive disorders in
men and women, psychologic disorders, and premature death.


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Diagnosis is based on body
mass index (BMI—calculated from height and weight) and waist circumference. BP, fasting
plasma glucose, and lipid levels should be measured. Treatment includes physical activity,
dietary and behavioral modification, and sometimes drugs or surgery.


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Prevalence of obesity in the US is high and is increasing, particularly among children and adolescents
(see
Table 6-1
). Prevalence is more than twice as high at age 55 as at age 20. Obesity is twice as common among women
in a lower socioeconomic group as among those in a higher group. Prevalence among black and white
men does not differ significantly, but it is higher among black women than white women. More than 50%
of black women ≥ 40 yr are obese; > 80% are overweight. In the US, obesity and its complications cause as many as 300,000 premature deaths each year, making
it second only to cigarette smoking as a preventable cause of death.


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[
Table 6-1. Changes in Prevalence of Obesity According to Nhanes]
Etiology
Almost all cases of obesity result from a combination of genetic predisposition and a chronic imbalance
between energy intake, energy utilization for basic metabolic processes, and energy expenditure from
physical activity. Genetic factors:
 Heritability of BMI is about 66%. Genetic factors may affect the many signaling
molecules and receptors used by parts of the hypothalamus and GI tract to regulate food intake (see
Sidebar 6-1
). Rarely, obesity results from abnormal levels of peptides that regulate food intake (eg, leptin)
or abnormalities in their receptors (eg, melanocortin-4 receptor). Genetic factors also regulate energy expenditure, including BMR, diet-induced thermogenesis, and
nonvoluntary activity-associated thermogenesis. Genetic factors may have a greater effect on the
distribution of body fat, particularly abdominal fat (see 
Metabolic Syndrome
 on p. 64
), than on the amount
of body fat.


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Environmental factors:
 Weight is gained when caloric intake exceeds energy needs. Important
determinants of energy intake include portion sizes and the energy density of the food. High-fat foods,
processed foods, and diets high in refined carbohydrates, soft drinks, fruit juices, and alcohol promote
weight gain. Diets high in fresh fruit and vegetables, fiber, and complex carbohydrates, with water as the
main fluid consumed, minimize weight gain. A sedentary lifestyle promotes weight gain. Regulatory factors:
 Prenatal maternal obesity, prenatal maternal smoking, intrauterine growth
restriction, and insufficient sleep can disturb weight regulation. About 15% of women permanently gain ≥
20 lb with each pregnancy.


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Obesity that persists beyond early childhood makes weight loss in later life
more difficult. Drugs, including corticosteroids, lithium, traditional antidepressants (tricyclics, tetracyclics, and
monoamine oxidase inhibitors [MAOIs]), benzodiazepines, and antipsychotic drugs, often cause weight
gain. Uncommonly, weight gain is caused by one of the following disorders:
The Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 6.


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string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. How can a balanced diet help prevent nutritional disorders?
3. What are the potential health risks of obesity related to nutritional imbalances?
4. What dietary changes can help treat iron deficiency anemia?
5. How do metabolic disorders impact nutrient absorption in the body?


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string_value:
1. What are the symptoms associated with vitamin deficiency disorders such as pellagra?
2. How can a deficiency in essential fatty acids impact overall health?
3. What dietary changes can help prevent kwashiorkor in at-risk populations?
4. What are the underlying causes of obesity related to nutrient imbalances?
5. How do micronutrient deficiencies affect metabolic functions in the body?


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string_value:
1. What are the potential health risks associated with excessive intake of saturated fats compared to unsaturated fats?
2. How can an imbalance in macronutrient consumption contribute to the development of obesity?
3. What symptoms might indicate a toxicity resulting from excessive intake of micronutrients?
4. In what ways do dietary carbohydrates impact energy levels and overall metabolic health?
5. What are the recommended dietary changes for individuals diagnosed with macronutrient-related disorders?


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string_value:
1. How do simple carbohydrates affect blood glucose levels compared to complex carbohydrates in individuals with diabetes?
2. What is the significance of the glycemic index in managing blood sugar levels for people with insulin resistance?
3. Can a diet high in complex carbohydrates help prevent obesity-related health issues?
4. What role do starches and fiber play in maintaining stable blood glucose levels in individuals with metabolic disorders?
5. How can understanding the differences between monosaccharides and disaccharides aid in dietary planning for those with nutritional deficiencies?


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string_value:
1. How do carbohydrates with a high glycemic index contribute to weight gain and obesity?
2. What is the relationship between insulin levels and hunger in individuals consuming high glycemic index foods?
3. How can a diet low in glycemic index carbohydrates potentially improve lipid profiles in patients?
4. What are the long-term health complications associated with consuming high glycemic index foods in relation to diabetes mellitus?
5. In what ways might dietary choices impact the risk of developing insulin resistance and metabolic disorders?


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string_value:
1. What are the symptoms associated with a deficiency in dietary proteins?
2. How can inadequate protein intake lead to metabolic disorders?
3. What dietary changes can be made to treat protein deficiency?
4. What are the potential health risks of excessive protein consumption?
5. How do amino acid imbalances affect overall health and nutrition?


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string_value:
1. What are the potential consequences of a negative nitrogen balance in the body?
2. How does starvation affect protein usage and nitrogen balance?
3. What role do proteins play in tissue maintenance and growth during periods of illness or injury?
4. What dietary changes can help improve a positive nitrogen balance in individuals experiencing catabolic states?
5. How can inadequate calorie intake lead to the body using protein for energy instead of tissue production?


key: chroma:document
string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. How can dietary changes help manage metabolic disorders?
3. What are the primary causes of obesity in adults?
4. What treatments are available for iron-deficiency anemia?
5. How can a lack of essential minerals affect overall health?


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string_value:
1. What are the potential health consequences of a deficiency in essential amino acids (EAAs) in infants compared to adults?
2. How does the dietary protein requirement change as a person ages from infancy to adulthood?
3. What symptoms might indicate a protein deficiency in children aged 5 years?
4. What dietary sources can provide the essential amino acids necessary for infants and children?
5. How can a lack of protein intake impact growth rates in young children?


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string_value:
1. How much additional protein do adults need to effectively increase muscle mass without risking nutritional imbalance?
2. What are the potential symptoms of protein deficiency in adults who are trying to build muscle?
3. Are there specific dietary deficiencies that can hinder muscle mass gain in adults?
4. What role do vitamins and minerals play in supporting muscle growth and recovery?
5. How can an adult balance their protein intake to avoid obesity while trying to increase muscle mass?


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1. How does the biological value of dietary proteins affect the risk of protein deficiency in individuals following a vegetarian or vegan diet?
2. What are the symptoms associated with a low biological value protein diet, and how can they be addressed through dietary adjustments?
3. What role does complementarity of proteins play in preventing nutritional disorders related to amino acid deficiencies?
4. How can individuals with metabolic disorders ensure they meet their protein needs considering the biological value of different protein sources?
5. What dietary strategies can be implemented to improve protein intake in populations at risk of malnutrition due to low biological value proteins?


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string_value:
1. How do trans fatty acids impact cholesterol levels and coronary artery disease risk?
2. What are the essential fatty acids and why are they important for the body?
3. Which dietary sources are high in ω-3 fatty acids, and how can they help reduce the risk of coronary artery disease?
4. What role do eicosanoids play in the body, and how are they related to essential fatty acids?
5. How does the consumption of saturated fats differ from that of unsaturated fats in terms of health effects?


key: chroma:document
string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. What dietary changes can help manage obesity and related health issues?
3. What are the potential causes of iron-deficiency anemia?
4. How can metabolic disorders affect nutrient absorption in the body?
5. What treatments are recommended for individuals with a vitamin B12 deficiency?


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string_value:
1. What are the essential fatty acid requirements for adults in terms of total caloric needs?  
2. How can deficiencies in linoleic and linolenic acids impact overall health in adults?  
3. What dietary sources are recommended for obtaining adequate amounts of linoleic acid?  
4. What are the potential symptoms of a deficiency in macrominerals such as calcium or magnesium?  
5. How do the requirements for essential fatty acids and macrominerals differ between age groups?  


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string_value:
1. How does dehydration affect physical performance and overall health?
2. What are the symptoms of water deficiency in the body?
3. How can increased physical activity influence daily water requirements?
4. What dietary changes can help prevent water-related nutritional disorders?
5. How does climate and humidity affect an individual's hydration needs?


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string_value:
[
    "What are the common symptoms of vitamin D deficiency?",
    "What dietary changes can help treat iron-deficiency anemia?",
    "What metabolic disorders are associated with obesity?",
    "What are the causes of calcium deficiency in adults?",
    "How can a balanced diet prevent nutritional disorders?"
]


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string_value:
1. What are the common symptoms associated with macromineral deficiencies in adults?
2. How can dietary imbalances in macrominerals lead to metabolic disorders?
3. What treatments are recommended for individuals suffering from obesity linked to nutritional disorders?
4. What are the primary causes of vitamin and mineral imbalances in children?
5. How can one identify and address dietary deficiencies of essential macrominerals?


key: chroma:document
string_value:
1. What are the common symptoms of vitamin D deficiency and how can they impact overall health?
2. What dietary changes can help address iron deficiency anemia?
3. How do certain micronutrient imbalances contribute to the development of obesity?
4. What are the recommended dietary allowances for magnesium and how do deficiencies affect metabolic health?
5. What treatments are available for individuals suffering from a vitamin B12 deficiency?


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string_value:
1. What are the symptoms of a deficiency in water-soluble vitamins, particularly vitamin C and the B complex vitamins?
2. How can the deficiency of essential trace minerals like iron and zinc impact metabolic health?
3. What dietary changes can be made to prevent deficiencies in fat-soluble vitamins such as vitamins A and D?
4. What are the potential health consequences of regularly consuming inadequate amounts of water-soluble vitamins?
5. How do metabolic disorders relate to imbalances in vitamin and mineral intake?


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string_value:
1. What are the potential health risks associated with excessive intake of trace minerals like arsenic and nickel?
2. How does fluoride contribute to dental health despite not being classified as an essential nutrient?
3. What symptoms might indicate a deficiency in essential trace minerals in the diet?
4. What dietary changes can help prevent the toxic effects of high levels of certain trace minerals?
5. How can an understanding of the 100,000 chemicals in our diet inform the management of nutritional disorders?


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string_value:
1. How does a low fiber intake contribute to the development of colon cancer?
2. What role does soluble fiber play in controlling blood glucose levels in individuals with diabetes?
3. What dietary changes can be recommended for patients suffering from functional bowel disorders?
4. How can increasing fiber consumption help manage obesity and its related health issues?
5. What are the potential health benefits of incorporating more fruits and vegetables into a typical Western diet?


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string_value:
1. How does a high fiber intake impact the absorption of essential minerals in the body?
2. What are the potential symptoms of a dietary deficiency caused by excessive fiber consumption?
3. What dietary changes can help improve body composition in individuals with nutritional disorders?
4. What are the recommended daily fiber intake levels for individuals with specific metabolic disorders?
5. How can increasing fiber intake contribute to better physical and mental work performance?


key: chroma:document
string_value:
1. How does an imbalance between energy intake and energy expenditure contribute to the development of obesity?
2. What role does age and sex play in determining an individual's energy expenditure?
3. What are the potential health consequences of consuming 100 calories more than needed each day over the course of a year?
4. How can individuals effectively manage their energy intake to prevent weight gain?
5. What dietary adjustments can help address metabolic disorders related to energy expenditure?


key: chroma:document
string_value:
1. What are the common symptoms associated with vitamin D deficiency, and how can they impact overall health?
2. What dietary changes can help manage obesity and promote weight loss effectively?
3. What are the primary causes of iron deficiency anemia, and what treatments are recommended for recovery?
4. How can metabolic disorders affect nutrient absorption, and what dietary interventions can mitigate these effects?
5. What are the potential health risks associated with prolonged deficiencies in B vitamins, and what dietary sources can help prevent these deficiencies?


key: chroma:document
string_value:
1. What are the common symptoms associated with vitamin D deficiency and how can they be treated?
2. What dietary changes can help manage obesity and its related health complications?
3. What are the primary causes of iron deficiency anemia and what nutritional interventions can be implemented?
4. How do metabolic disorders impact nutrient absorption and what dietary strategies can be employed to mitigate these effects?
5. What are the signs of a vitamin B12 deficiency and what foods can help restore adequate levels?


key: chroma:document
string_value:
1. What are the recommended dietary reference intakes (DRIs) for essential nutrients based on age and sex?
2. How does metabolic rate influence daily dietary requirements for vitamins and minerals?
3. What are the potential symptoms of vitamin D deficiency in different age groups?
4. How can an imbalance in dietary protein intake affect physical activity levels?
5. What dietary changes can be made to address iron deficiency anemia?


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string_value:
1. What are the common nutritional deficiencies experienced by pregnant women, and how can they impact fetal development?
2. How can obesity during pregnancy affect maternal and fetal health outcomes?
3. What symptoms indicate a potential vitamin D deficiency in pregnant women?
4. What dietary changes can pregnant women implement to prevent iron deficiency anemia?
5. How do metabolic disorders influence nutritional needs during pregnancy?


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string_value:
1. What are the recommended daily servings of food groups for different age groups according to the USDA Food Guide Pyramid?
2. How does aging affect nutritional needs and energy expenditure?
3. What dietary changes can help in reducing the intake of saturated fats and trans fatty acids?
4. What role do whole grains, vegetables, and fruits play in preventing nutritional disorders?
5. How can regular exercise contribute to maintaining a healthy diet and preventing obesity?


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string_value:
1. How does excessive intake of saturated fats contribute to the development of atherosclerosis?
2. What are the benefits of substituting polyunsaturated fatty acids for saturated fats in the diet?
3. Are there specific symptoms associated with atherosclerosis that can be linked to dietary choices?
4. What potential risks are associated with routine use of nutritional supplements in individuals at risk for atherosclerosis?
5. How can dietary changes help in the management or prevention of atherosclerosis?


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string_value:
1. What are the symptoms and health risks associated with hypervitaminosis A?
2. How can malabsorption contribute to nutritional deficiencies in patients?
3. What dietary restrictions are necessary for individuals with phenylketonuria?
4. What are the indications for conducting a nutritional evaluation in elderly patients?
5. How does overnutrition relate to the development of chronic disorders such as obesity and diabetes mellitus?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. How can a high-sugar diet contribute to the development of metabolic disorders?
3. What dietary changes can help manage obesity in adults?
4. What are the primary causes of iron deficiency anemia, and how can it be treated?
5. How do imbalances in essential fatty acids affect overall health?


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string_value:
1. What laboratory tests are commonly used to confirm undernutrition in patients?
2. How can skinfold measurements help in evaluating obesity and nutritional status?
3. What are the potential health consequences of low albumin levels in individuals suspected of undernutrition?
4. How does bioelectrical impedance analysis estimate body fat percentage in nutritional assessments?
5. What symptoms might indicate a vitamin or mineral deficiency in an individual?


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string_value:
1. What dietary intake patterns are most commonly associated with nutritional deficiencies in adults?  
2. How can significant weight changes indicate potential nutritional disorders?  
3. What specific risk factors should be evaluated to assess an individual's likelihood of developing nutritional deficiencies?  
4. In what ways can a food diary contribute to the diagnosis of metabolic disorders?  
5. How does the body mass index (BMI) relate to the risk of obesity and associated nutritional health issues?  


key: chroma:document
string_value:
1. What are the common symptoms of nutritional disorders in infants and how can they be identified?
2. What dietary deficiencies are most likely to affect children during their growth phases?
3. How can obesity in adolescents be linked to nutritional disorders, and what are effective treatment options?
4. What are the primary causes of vitamin and mineral imbalances in children and adolescents?
5. How can parents ensure adequate weight gain in infants while preventing nutritional disorders?


key: chroma:document
string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. What dietary changes can help manage obesity and promote weight loss?
3. What are the potential causes of iron deficiency anemia in adults?
4. How can a deficiency in vitamin B12 affect neurological function?
5. What treatment options are available for individuals diagnosed with metabolic syndrome?


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string_value:
1. How does truncal obesity contribute to the risk of developing diabetes and hypertension?
2. What waist circumference measurements indicate a higher risk for cardiovascular disorders in men and women?
3. In patients with a BMI of less than 35, how can waist circumference be used to assess obesity-related health risks?
4. What are the potential nutrient-drug interactions that could affect a patient's nutritional status?
5. How does the distribution of body fat influence the likelihood of cerebrovascular disorders?


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1. How do high-protein diets affect the metabolism of certain medications?
2. Which foods are known to impair the absorption of antibiotics?
3. What role does grapefruit play in the metabolism of drugs like amiodarone and carbamazepine?
4. How can alterations in bacterial flora influence the overall metabolism of medications?
5. What dietary changes can be recommended to optimize drug absorption and metabolism in patients?


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string_value:
1. How does tyramine in cheese interact with monoamine oxidase inhibitors, and what are the potential health risks?
2. What nutritional deficiencies can impair drug absorption and metabolism, and what are their consequences on health?
3. In what ways can changes in the gastrointestinal tract affect the efficacy of medications?
4. How does a deficiency in vitamins and minerals like calcium, magnesium, zinc, and vitamin C influence drug metabolism in the elderly?
5. What impact do various drugs have on appetite and food absorption in individuals with nutritional disorders?


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1. How do certain medications affect the absorption of nutrients in patients with gastrointestinal disorders?
2. What is the impact of decreased gastrointestinal motility on nutrient absorption and overall nutrition?
3. Which drugs are recommended to be taken with food to improve patient tolerance and nutrient absorption?
4. What are the potential nutritional deficiencies associated with the use of opioids and anticholinergics?
5. How can increased GI motility from medications like metoclopramide lead to dietary challenges for patients?


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1. How do thiazide diuretics influence potassium levels and what are the potential cardiovascular implications?
2. What role do corticosteroids play in sodium and water retention, and how might this affect patients with certain health conditions?
3. How can the repeated use of laxatives lead to potassium depletion, and what symptoms might arise from this deficiency?
4. In what ways can sulfonylureas and lithium impact thyroid function related to iodine metabolism?
5. What dietary recommendations can help mitigate the risks associated with potassium depletion from diuretic use?


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1. How do oral contraceptives affect zinc and copper levels in the body?
2. What impact do tetracycline antibiotics have on iron absorption from food?
3. Which foods are known to inhibit iron absorption, and how do they do so?
4. What symptoms might indicate a deficiency in zinc or an imbalance in copper levels?
5. Are there any specific dietary recommendations for individuals taking antibiotics that affect nutrient absorption?


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1. How does ethanol consumption affect the absorption and utilization of thiamin in the body?
2. What role do oral contraceptives play in inhibiting folate metabolism?
3. How does isoniazid interfere with the metabolism of niacin and pyridoxine?
4. What are the potential health consequences of impaired vitamin absorption due to drug interactions?
5. Which dietary modifications can help mitigate the effects of ethanol on vitamin utilization?


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1. What are the potential nutritional deficiencies associated with the use of anticonvulsant medications like phenytoin and phenobarbital?
2. How might folate supplements affect the effectiveness of phenytoin in patients with folate deficiency?
3. What are the consequences of vitamin D deficiency in patients taking anticonvulsants?
4. Which medications are known to cause malabsorption of vitamin B12, and what symptoms might this lead to?
5. How can high doses of progestin in oral contraceptives contribute to depressive symptoms in women?


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1. How do certain food additives contribute to the development of obesity and related metabolic disorders?
2. What are the potential symptoms associated with dietary deficiencies caused by food additives in processed foods?
3. Can the consumption of specific food additives lead to vitamin and mineral imbalances in the body?
4. What role do food contaminants play in exacerbating nutritional disorders?
5. How can individuals mitigate the risks of nutritional disorders linked to food additives in their diet?


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1. What are the potential health risks associated with the consumption of nitrites in cured meats?
2. How do dietary vitamin C levels influence nitrite formation in the gastrointestinal tract?
3. What symptoms might indicate a hypersensitivity reaction to food additives like sulfites?
4. How does the use of food additives impact the nutritional value of commercially prepared foods?
5. What role do naturally occurring food nitrates play in the body compared to added nitrites?


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1. What are the potential health effects of consuming foods contaminated with heavy metals like lead and mercury?
2. How do pesticide residues in food contribute to the development of nutritional disorders?
3. What symptoms might indicate a dietary deficiency caused by contaminants in commonly consumed foods?
4. Are there specific nutritional disorders associated with the consumption of aflatoxin-contaminated nuts and milk?
5. What dietary modifications can be made to reduce exposure to growth-promoting hormones in dairy products and meat?


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1. What are the potential long-term adverse effects of extremely low nutrient exposures in individuals with nutritional disorders?
2. How are safe levels of nutrient intake determined for populations at risk of dietary deficiencies?
3. What symptoms may arise from prolonged low levels of essential vitamins and minerals?
4. What causal relationships exist between specific dietary deficiencies and the development of metabolic disorders?
5. How can obesity be linked to vitamin and mineral imbalances in the diet?


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1. What are the common symptoms associated with vitamin D deficiency and how can they impact overall health?
2. What dietary changes are recommended for individuals suffering from metabolic syndrome?
3. How can obesity contribute to the development of nutritional disorders, and what strategies can be implemented for effective weight management?
4. What are the potential causes of iron deficiency anemia, and what treatments are available to address this condition?
5. How do various vitamin and mineral imbalances affect bodily functions, and what dietary sources can help restore balance?


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1. What are the primary causes of undernutrition and how do they differ from those of overnutrition?
2. How do the stages of undernutrition progress, and what are the observable symptoms at each stage?
3. What risk factors are associated with undernutrition in specific populations, such as infants and the elderly?
4. How can undernutrition impact metabolic functions and nutrient absorption in the body?
5. What interventions or treatments are recommended for individuals experiencing undernutrition?


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1. What are the potential consequences of vitamin K deficiency in neonates?
2. How does the high energy demand in infants contribute to their susceptibility to undernutrition?
3. What is the recommended treatment for preventing hemorrhagic disease of the newborn?
4. Why are infants given a vitamin K injection shortly after birth?
5. What are the symptoms associated with undernutrition in infancy and childhood?


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1. What are the potential consequences of vitamin B12 deficiency in infants who are exclusively breastfed by vegan mothers?
2. How can protein-energy undernutrition (PEU) be identified in inadequately fed infants and children?
3. What vitamins and minerals are commonly deficient in children suffering from undernutrition?
4. Why do adolescents have increased nutritional requirements and what are the implications of not meeting these needs?
5. What dietary interventions can help prevent vitamin D deficiency in breastfed infants?


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1. What are the common symptoms of anorexia nervosa in adolescent girls?
2. What factors contribute to the development of anorexia nervosa in young individuals?
3. How can anorexia nervosa impact the nutritional health of adolescents?
4. What treatment options are available for individuals diagnosed with anorexia nervosa?
5. What role do dietary deficiencies play in the progression of anorexia nervosa?


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1. What are the common nutritional deficiencies that can occur during pregnancy and breastfeeding?
2. How does pica affect the nutritional status of pregnant women?
3. What are the symptoms and causes of iron deficiency anemia in pregnant women?
4. How can folate deficiency anemia be prevented in women who have taken oral contraceptives?
5. What dietary changes can help address nutritional imbalances during pregnancy and breastfeeding?


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string_value:
1. What are the potential consequences of vitamin D deficiency during pregnancy on a child's bone health?
2. How does aging contribute to the development of sarcopenia and its associated complications?
3. What lifestyle factors can exacerbate sarcopenia in older adults?
4. How do hormonal changes in men contribute to muscle loss as they age?
5. In what ways does aging affect body composition and metabolic rate in older adults?


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string_value:
1. What are the physiological changes in the stomach that contribute to anorexia in aging individuals?
2. How does the release and activity of certain hormones affect appetite in older adults?
3. What are some potential treatments for anorexia related to aging?
4. How can dietary deficiencies in older adults lead to undernutrition?
5. What role does metabolism play in the development of nutritional disorders among the elderly?


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1. How do hormones like cholecystokinin and leptin influence appetite and satiety in individuals with nutritional disorders?
2. What role do diminished taste and smell play in the eating habits of those suffering from anorexia?
3. What are some psychological and social factors that can contribute to the development of anorexia?
4. How can chronic disorders and certain medications affect a person's eating behavior and nutritional intake?
5. What interventions can be implemented to support individuals with anorexia who struggle with meal preparation and shopping?


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1. What psychological factors can contribute to eating difficulties in the elderly, such as depression or mania?
2. How do dental problems impact the ability to consume and digest food in older adults?
3. What are the common swallowing difficulties faced by individuals with neurological disorders, and how do they affect nutrition?
4. In what ways does poverty influence access to adequate nutrition, particularly in institutionalized elderly populations?
5. How can confusion in elderly individuals lead to unrecognized hunger or food preferences, and what interventions can be implemented to address this issue?


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1. What are the common causes of nutritional disorders that lead to an inability to feed oneself?
2. How can caregivers assist individuals with physical limitations in maintaining proper nutrition?
3. What symptoms should be monitored in individuals who may be unable to feed themselves due to a nutritional disorder?
4. What dietary modifications can help manage obesity in individuals with feeding difficulties?
5. What treatment options are available for addressing vitamin and mineral imbalances in those with nutritional disorders?


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string_value:
1. What factors contribute to inadequate vitamin D intake in the elderly population?  
2. How does osteomalacia manifest in institutionalized elderly individuals?  
3. What dietary changes can help improve vitamin D absorption in older adults?  
4. What are the potential consequences of insufficient vitamin D synthesis in the elderly?  
5. How can caregivers assist elderly individuals who have difficulty chewing or swallowing to ensure adequate nutrition?  


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1. How do chronic gastrointestinal disorders affect the absorption of fat-soluble vitamins and minerals?
2. What are the potential nutritional deficiencies associated with renal insufficiency?
3. How can a vegan diet lead to vitamin B12 deficiency, and what are some dietary sources to prevent this?
4. What impact do infections and prolonged fever have on metabolic demands and nutritional status?
5. In what ways can anorexia in cancer patients contribute to nutritional deficiencies?


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1. What are the potential health risks associated with following a fruit-only diet?
2. How can certain drugs impair nutrient absorption and lead to nutritional deficiencies?
3. What symptoms might indicate a magnesium deficiency in individuals with alcohol dependency?
4. How do very low calorie diets impact long-term health and nutritional status?
5. What are the signs of nutritional deficiency that can occur due to drug dependency?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. How does obesity impact the risk of developing metabolic disorders?
3. What dietary changes can help address iron deficiency anemia?
4. What are the potential causes of vitamin B12 deficiency in adults?
5. How can individuals prevent nutritional disorders related to inadequate calcium intake?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. What dietary changes can help manage iron deficiency anemia?
3. What are the potential causes of metabolic syndrome in adults?
4. How does obesity impact the risk of developing type 2 diabetes?
5. What treatment options are available for individuals with vitamin B12 deficiency?


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string_value:
1. What are the common symptoms associated with undernutrition in adults?
2. What dietary changes can help address vitamin and mineral deficiencies in children?
3. What are the potential causes of obesity as a nutritional disorder?
4. How can metabolic disorders influence an individual's nutritional needs?
5. What treatment options are available for individuals suffering from severe protein-energy malnutrition?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. How can body composition analysis help in diagnosing nutritional disorders?
3. What laboratory tests are typically used to identify metabolic disorders related to nutrition?
4. What dietary changes are recommended for individuals diagnosed with obesity?
5. What role do medical and diet histories play in the diagnosis of nutritional disorders?


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1. What dietary changes may have contributed to a recent unintentional weight loss of more than 10% in the past three months?
2. How does impaired night vision relate to potential vitamin A deficiency?
3. What are the key risk factors for undernutrition that should be assessed in a patient's social history?
4. What anthropometric measurements can be used to evaluate lean body mass and body fat distribution in assessing nutritional status?
5. How can alcohol and drug use impact an individual's nutritional intake and overall health?


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1. What are the potential health risks associated with a BMI of 18 or lower?
2. How can undernutrition be diagnosed using body mass index (BMI)?
3. What factors can contribute to a weight that is less than 80% of the predicted weight for a patient's height?
4. What are the common symptoms of undernutrition in adults?
5. What dietary changes can help address undernutrition and improve BMI?


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1. How can the mid upper arm muscle area be used to assess lean body mass in patients with nutritional disorders?
2. What are the implications of having a mid upper arm muscle area value below 75% of the standard for men and women?
3. What factors may contribute to a decrease in mid upper arm circumference and triceps skinfold thickness in individuals with nutritional deficiencies?
4. How does the measurement of mid upper arm muscle area help in diagnosing conditions related to obesity or malnutrition?
5. What dietary interventions can help improve lean body mass in individuals with a depleted mid upper arm muscle area?


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1. How do physical activity levels influence the risk of developing nutritional disorders related to muscle loss?
2. What genetic factors are associated with specific nutritional deficiencies or metabolic disorders?
3. What age-related changes can contribute to vitamin and mineral imbalances in older adults?
4. What are the common symptoms of obesity that may be linked to nutritional disorders?
5. What dietary treatments are recommended for addressing muscle loss due to nutritional deficiencies?


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1. What physical examination signs should be assessed to identify nutritional deficiencies in patients?
2. How can mental status impact nutritional health and contribute to weight loss?
3. What are the key components of the Subjective Global Assessment (SGA) used to evaluate a patient's nutritional status?
4. In what ways can dental problems predispose individuals to nutritional deficiencies?
5. How does the Mini Nutritional Assessment (MNA) differ from the Simplified Nutrition Assessment Questionnaire (SNAQ) in assessing nutritional risk?


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1. What are the common symptoms associated with vitamin D deficiency, and how can they impact overall health?
2. How can a wilderness survival situation lead to specific nutritional disorders, and what immediate corrective measures can be taken?
3. What laboratory tests are typically recommended to diagnose nutritional disorders in patients with unclear symptoms?
4. What are the metabolic implications of prolonged dietary deficiencies, and how can they be effectively addressed?
5. How does obesity affect the risk of developing nutritional disorders, and what dietary changes can help mitigate this risk?


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1. What laboratory tests are commonly used to assess protein deficiency in patients with undernutrition?
2. How do decreases in serum albumin and prealbumin levels correlate with the progression of undernutrition?
3. What are the clinical implications of low transferrin and retinol-binding protein levels in patients?
4. What factors may contribute to protein-energy undernutrition (PEU) in individuals?
5. How can the measurement of serum albumin inform treatment strategies for patients experiencing undernutrition?


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1. How do inflammation and cytokines affect serum albumin levels in patients with nutritional disorders?  
2. What role do prealbumin, transferrin, and retinol-binding protein play in diagnosing acute starvation?  
3. Why might total lymphocyte count be unreliable in assessing undernutrition in AIDS patients?  
4. How can skin tests using antigens be used to detect impaired cell-mediated immunity in individuals with protein-energy undernutrition (PEU)?  
5. What are the implications of decreased CD4+ T lymphocytes in patients suffering from undernutrition?  


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string_value:
1. What specific laboratory tests can be used to diagnose vitamin deficiencies in patients?
2. How can a deficiency in certain minerals affect overall health and metabolism?
3. What are the common symptoms associated with vitamin D deficiency?
4. What dietary changes can help address iron deficiency anemia?
5. What role do laboratory tests play in identifying the causes of obesity-related metabolic disorders?


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    "What dietary changes can help manage obesity effectively?",
    "What are the primary causes of iron deficiency anemia?",
    "How can a metabolic disorder affect nutrient absorption?",
    "What treatment options are available for individuals with vitamin B12 deficiency?"
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1. What are the common symptoms associated with protein-energy undernutrition in adults?
2. What are the potential causes of protein-energy undernutrition?
3. How can dietary deficiencies contribute to the development of protein-energy undernutrition?
4. What are the recommended treatments for individuals diagnosed with protein-energy undernutrition?
5. How does protein-energy undernutrition affect micronutrient levels in the body?


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1. What are the common symptoms associated with severe protein-energy undernutrition (PEU)?
2. What are the potential causes of gradual protein-energy undernutrition in adults?
3. How can subclinical deficiencies in nutrition be identified before they progress to more severe conditions?
4. What dietary changes can help prevent the development of starvation-related symptoms in individuals at risk?
5. How does edema present in individuals suffering from significant nutritional deficiencies?


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1. What are the common symptoms associated with multiple organ impairment due to nutritional disorders?
2. What dietary deficiencies can lead to the impairment of multiple organ systems?
3. How can vitamin and mineral imbalances contribute to the development of metabolic disorders?
4. What are the potential causes of obesity related to nutritional imbalances?
5. What treatment options are available for individuals experiencing multiple organ system impairment due to nutritional disorders?


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string_value:
1. What laboratory tests are typically used to diagnose Protein-Energy Under-nutrition (PEU)?
2. How does the classification of PEU into mild, moderate, and severe grades affect treatment approaches?
3. What are the common causes of PEU in institutionalized elderly patients?
4. How can nutrient deficiencies in children from developing countries lead to severe PEU?
5. What role do IV solutions play in the initial treatment of fluid and electrolyte deficits in PEU patients?


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1. What are the primary causes of protein-energy undernutrition (PEU) in children and the elderly?
2. How do marasmus and kwashiorkor differ in terms of symptoms and underlying causes?
3. What role does depression play in the development of secondary protein-energy undernutrition in the elderly?
4. What are the potential health consequences of chronic starvation or anorexia nervosa in relation to primary PEU?
5. How can child or elder abuse contribute to the onset of protein-energy undernutrition?


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1. What are the primary differences in symptoms between kwashiorkor and marasmus?
2. What dietary factors contribute to the development of kwashiorkor in children?
3. How does an acute illness, such as gastroenteritis, influence the risk of developing kwashiorkor?
4. In which geographical regions is kwashiorkor most commonly found, and why?
5. What are the physiological effects of protein deficiency on cell membranes in individuals with kwashiorkor?


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1. What are the primary causes of primary protein-energy undernutrition (PEU) in individuals experiencing fasting or anorexia nervosa?
2. How do gastrointestinal disorders contribute to secondary protein-energy undernutrition (PEU)?
3. What role do wasting disorders like AIDS and cancer play in the development of cachexia and its impact on nutritional status?
4. How does cardiac cachexia differ from other forms of undernutrition, and what are its specific contributing factors?
5. What treatment options are available for individuals suffering from protein-energy undernutrition due to malabsorption or chronic illness?


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1. What are the metabolic demands associated with infections and how do they affect nutritional needs?
2. How does hyperthyroidism influence dietary requirements and potential nutritional deficiencies?
3. What role do endocrine disorders play in the development of metabolic disorders and related nutritional imbalances?
4. In cases of trauma or burns, what specific nutritional interventions are recommended to meet increased metabolic demands?
5. How can surgical patients manage their nutritional intake to prevent complications related to altered metabolism?


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1. What are the potential health consequences of using protein for energy when adipose tissue is depleted?
2. How does a negative nitrogen balance affect muscle and organ health in individuals with nutritional disorders?
3. What dietary changes can help prevent the breakdown of visceral organs and muscle tissue in cases of energy deficiency?
4. What are the symptoms associated with a negative nitrogen balance due to inadequate nutritional intake?
5. What treatments are effective for restoring balance in individuals experiencing weight loss from protein catabolism?


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1. What are the common symptoms associated with moderate protein-energy undernutrition (PEU)?
2. How does loss of organ weight vary among different organs in cases of nutritional disorders?
3. What are the potential causes of apathy and irritability in individuals suffering from nutritional deficiencies?
4. What organ systems are most affected by moderate PEU, and what specific symptoms can arise from these effects?
5. What dietary interventions can help address the symptoms associated with moderate protein-energy undernutrition?


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1. What nutritional deficiencies could lead to weakness and decreased work capacity in a patient?  
2. How can specific dietary changes help improve symptoms of weakness in individuals with nutritional disorders?  
3. What are the potential metabolic disorders that could cause fatigue and reduced physical performance?  
4. Which vitamins and minerals are essential for maintaining energy levels and preventing weakness?  
5. What treatment options are available for addressing weakness related to nutritional imbalances?  


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1. What are the common symptoms associated with temporary lactose deficiency?  
2. How does achlorhydria contribute to digestive issues in individuals with nutritional disorders?  
3. What role do intestinal disaccharidases, particularly lactase, play in the digestion of carbohydrates?  
4. What dietary changes can help manage diarrhea related to lactose deficiency?  
5. How can cognitive impairment be linked to nutritional disorders?  


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string_value:
1. What are the symptoms of protein-energy undernutrition (PEU) in adults?
2. How does prolonged starvation affect weight loss in adults and children?
3. What are the effects of PEU on reproductive health in both men and women?
4. How does cachexia manifest in individuals with severe nutritional deficiencies?
5. What are the potential complications related to skin and hair health in individuals suffering from PEU?


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string_value:
1. How does protein-energy undernutrition (PEU) affect heart size and cardiac output in elderly patients?  
2. What are the primary risk factors for developing hip fractures in elderly individuals with nutritional deficiencies?  
3. What preventive measures can be taken to reduce the incidence of pressure ulcers in malnourished patients?  
4. What are the potential symptoms associated with severe protein-energy undernutrition in the elderly?  
5. How can dietary interventions improve the overall health outcomes of elderly patients at risk for nutritional disorders?  


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string_value:
1. What are the common symptoms associated with protein-energy undernutrition?
2. How does protein-energy undernutrition affect respiratory rate and vital capacity?
3. What factors contribute to the development of protein-energy undernutrition in individuals?
4. What treatment options are available for managing protein-energy undernutrition?
5. How can dietary deficiencies lead to metabolic disorders related to protein-energy undernutrition?


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string_value:
1. What are the primary symptoms associated with protein-energy undernutrition (PEU) in infants and adults?
2. How does cell-mediated immunity impairment in nutritional disorders increase susceptibility to infections?
3. What are the potential complications of severe nutritional deficiencies, such as liver or kidney failure?
4. How can marasmus in infants impact their growth and physical development?
5. What role do cytokines play in the progression of symptoms related to nutritional disorders?


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1. What are the primary symptoms associated with Kwashiorkor?
2. How does Kwashiorkor affect abdominal muscles and liver size?
3. What are the potential causes of peripheral and periorbital edema in individuals with Kwashiorkor?
4. In what ways can the skin change in appearance due to Kwashiorkor?
5. What nutritional deficiencies are commonly linked to the development of Kwashiorkor?


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string_value:
1. What nutritional deficiencies could lead to changes in hair texture and coloration, such as thinning or a "striped flag" appearance?
2. How do episodes of undernutrition affect the overall health and behavior of children with nutritional disorders?
3. What are the potential causes of excessive eyelash hair growth in individuals experiencing nutritional disorders?
4. What treatments or dietary interventions can help restore hair health in children with nutritional imbalances?
5. How does the irritability of affected children when held relate to their nutritional status and overall well-being?


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string_value:
1. What are the key indicators used to diagnose Protein-Energy Undernutrition (PEU)?
2. How does a low serum albumin level impact the severity assessment of nutritional disorders?
3. What symptoms might not develop in cases of total starvation within 8 to 12 weeks?
4. Why is it important to identify the cause of inadequate dietary intake in children?
5. What laboratory tests are essential for diagnosing complications associated with nutritional disorders?


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string_value:
1. What are the physical examination findings that can help confirm a diagnosis of anorexia nervosa in children and adolescents?
2. How can child abuse be linked to the development of anorexia nervosa in young individuals?
3. What are the common symptoms of anorexia nervosa that may be observed during a physical examination?
4. What treatment options are available for children and adolescents diagnosed with anorexia nervosa?
5. What dietary deficiencies are commonly associated with anorexia nervosa in children and adolescents?


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string_value:
1. What laboratory tests are recommended to confirm a diagnosis of protein-energy undernutrition (PEU) when dietary history is inconclusive?  
2. How can serum albumin and total lymphocyte count assist in assessing the severity of nutritional disorders?  
3. What are the potential abnormal test results that may indicate underlying nutritional deficiencies in individuals with PEU?  
4. How do urinary creatinine and methylhistidine levels relate to muscle wasting in the context of nutritional disorders?  
5. What role does protein catabolism play in the interpretation of urinary urea levels in patients with nutritional deficiencies?  


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string_value:
1. What laboratory tests are recommended to identify causes of suspected secondary protein-energy undernutrition (PEU)?
2. How can C-reactive protein levels help in understanding the underlying causes of undernutrition?
3. What role do cytokines play in the assessment of nutritional disorders?
4. When should thyroid function tests be considered in the evaluation of undernutrition?
5. What are the potential implications of cytokine excess on the treatment of nutritional disorders?


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string_value:
1. What laboratory tests are recommended to assess for abnormalities associated with nutritional disorders?  
2. How do serum electrolyte levels relate to the diagnosis of nutritional deficiencies?  
3. What types of anemia are commonly associated with nutritional disorders, and what are their causes?  
4. What role does metabolic acidosis play in the context of nutritional disorders?  
5. How can low levels of serum glucose and electrolytes affect overall health in individuals with nutritional deficiencies?  


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string_value:
1. What are the common symptoms associated with undernutrition in adults and children?
2. What are the potential causes of undernutrition in developing countries?
3. How can undernutrition affect the immune system and overall health?
4. What dietary changes are recommended for individuals recovering from undernutrition?
5. How does undernutrition differ from malnutrition in terms of treatment and prevention?


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1. What are the potential causes of severe diarrhea in individuals with nutritional disorders?
2. How can stool cultures help in diagnosing underlying infections in patients with protein-energy undernutrition (PEU)?
3. What is the significance of obtaining urinalysis and blood cultures in the context of nutritional deficiencies?
4. What is the range of mortality rates for children diagnosed with protein-energy undernutrition?
5. How does a muted response to infections affect the treatment approach for patients with nutritional disorders?


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1. What are the common causes of mortality in children with mild Protein-Energy Undernutrition (PEU) during the initial days of treatment?
2. How do electrolyte deficits contribute to the complications observed in children suffering from nutritional disorders?
3. What are the key signs that indicate a worsening condition in children with nutritional deficiencies?
4. What intensive care measures can reduce mortality rates in children diagnosed with PEU?
5. How does persistent diarrhea affect the nutritional status and overall health of children?


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1. What are the key signs and symptoms of protein-energy undernutrition (PEU) in children and adults?
2. How does recovery from kwashiorkor compare to recovery from marasmus in terms of speed and effectiveness?
3. What long-term effects can protein-energy undernutrition have on cognitive development in young children?
4. How does protein-energy undernutrition increase morbidity and mortality risks in elderly patients?
5. What are the potential complications associated with chronic malabsorption and pancreatic insufficiency in individuals with PEU?


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1. What are the recommended treatment options for mild or moderate protein-energy undernutrition (PEU)?
2. How can lactose intolerance affect the dietary management of children experiencing persistent diarrhea?
3. What role does supportive care play in the treatment of nutritional disorders?
4. What preventive strategies are most effective in addressing nutritional disorders globally?
5. When is it appropriate to use liquid oral food supplements instead of solid food in nutritional treatment?


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string_value:
1. What dietary adjustments should be made for patients experiencing diarrhea due to lactose intolerance?  
2. How does starvation affect the risk of developing infectious diarrhea in individuals with gastrointestinal disorders?  
3. What role does yogurt play in the diet of individuals with lactose intolerance compared to milk-based formulas?  
4. Why is it important to provide a multivitamin supplement to patients experiencing persistent diarrhea?  
5. What are the potential complications of diarrhea in relation to nutrient absorption in the gastrointestinal tract?  


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1. What are the primary symptoms of severe protein-energy undernutrition (PEU) in adults?
2. How does prolonged starvation affect fluid and electrolyte balance in the body?
3. What dietary interventions are recommended for patients with severe PEU in a hospital setting?
4. What are the potential causes of prolonged starvation leading to nutritional disorders?
5. How can electrolyte abnormalities be identified and corrected in patients suffering from severe PEU?


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1. What are the recommended methods for supplying macronutrients to patients with swallowing difficulties due to nutritional disorders?  
2. When is parenteral nutrition indicated for patients suffering from severe malabsorption?  
3. How can infections related to nutritional disorders be effectively treated?  
4. What types of feeding tubes are commonly used for patients who cannot swallow?  
5. What are the potential health consequences of vitamin and mineral imbalances in individuals with nutritional disorders?  


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1. What are the recommended micronutrient dosages for patients recovering from nutritional disorders?
2. How should feeding be managed for children experiencing diarrhea to prevent worsening of their condition?
3. What are the signs of specific nutrient deficiencies that may arise as a patient’s weight increases during recovery?
4. What types of feeding strategies are recommended for children with limited intestinal absorptive capacity?
5. How should underlying disorders be addressed in conjunction with treating nutritional deficiencies in children?


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1. What is the recommended caloric and protein intake for children with protein-energy undernutrition (PEU)?
2. How are micronutrient deficiencies addressed in the treatment of nutritional disorders?
3. What dietary changes should be made after the initial four weeks of formula feeding for a child recovering from PEU?
4. What is the importance of energy distribution among macronutrients in the diet of children with nutritional disorders?
5. Why is iron supplementation often necessary for children with protein-energy undernutrition?


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1. What are the potential effects of excess cytokine production on nutritional intake in adults with underlying disorders?
2. How can megestrol acetate or medroxyprogesterone improve food intake in patients with AIDS or cancer?
3. What are the risks associated with using megestrol acetate or medroxyprogesterone for more than three months?
4. How does testosterone replacement therapy help mitigate muscle loss in men treated with megestrol acetate or medroxyprogesterone?
5. What are the signs and symptoms of adrenal insufficiency that may arise from short-term use of certain medications for nutritional disorders?


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1. What are the recommended interventions for patients with anorexia when the underlying cause is unknown?
2. How can anabolic steroids or growth hormone aid in the treatment of cachexia in patients with renal failure?
3. What role does home delivery of meals play in managing nutritional disorders for patients with functional limitations?
4. In what situations should dronabinol be considered for patients experiencing anorexia?
5. How does the correction of protein-energy undernutrition (PEU) in adults differ from that in children?


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1. What are the common symptoms associated with vitamin D deficiency in adults?
2. How can metabolic disorders affect nutrient absorption in the body?
3. What dietary changes can help manage obesity-related nutritional disorders?
4. What are the potential causes of iron deficiency anemia, and how can it be treated?
5. How do imbalances in essential minerals impact overall health and wellness?


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1. What is the recommended daily caloric and protein intake for patients with protein-energy undernutrition (PEU)?
2. How can environmental modifications improve food intake in institutionalized elderly patients?
3. What are the potential benefits and drawbacks of using gastrostomy tube feeding in patients with severe dysphagia?
4. What role do orexigenics and anabolic steroids play in the treatment of protein-energy undernutrition?
5. Why is it important to avoid unpalatable therapeutic diets in institutionalized patients with nutritional disorders?


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1. What are the common symptoms associated with undernutrition in adults and children?
2. What are the primary causes of undernutrition in developing countries?
3. How can undernutrition impact the immune system and overall health?
4. What dietary changes are recommended to prevent or treat undernutrition?
5. How does undernutrition differ in its effects on physical and mental health?


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1. What are the potential complications associated with the treatment of Protein-Energy Under-nutrition (PEU)?
2. How can refeeding syndrome impact patients who are being treated for PEU?
3. What are the possible causes of diarrhea in patients undergoing treatment for PEU?
4. Why is it important to monitor electrolyte levels during the treatment of PEU?
5. How can hydration management be complicated by pre-existing cardiac or renal conditions in patients with PEU?


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1. What are the potential cardiovascular effects of potassium or magnesium depletion in patients receiving parenteral feeding?
2. How does carbohydrate metabolism during treatment influence phosphate levels in the body?
3. What symptoms might indicate hypophosphatemia in patients undergoing nutritional therapy?
4. Why is it important to regularly monitor phosphate levels during parenteral feeding?
5. What complications can arise from ineffective endogenous insulin during nutritional treatment, particularly concerning blood sugar levels?


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1. What are the symptoms of dehydration and hyperosmolarity in individuals with nutritional disorders?
2. What dietary factors can lead to dehydration and hyperosmolarity?
3. How can dehydration and hyperosmolarity be treated in patients suffering from nutritional disorders?
4. What role do vitamins and minerals play in preventing dehydration and hyperosmolarity?
5. How does obesity contribute to the risk of developing dehydration and hyperosmolarity?


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1. What are the potential symptoms associated with carnitine deficiency?
2. How can a prolonged QT interval be related to nutritional disorders?
3. What dietary sources are rich in carnitine to prevent deficiency?
4. What treatments are available for individuals diagnosed with carnitine deficiency?
5. How does carnitine deficiency contribute to the development of fatal ventricular arrhythmias?


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1. What are the common symptoms associated with carnitine deficiency in infants?
2. How can inadequate intake of carnitine lead to metabolic disorders?
3. What dietary sources are rich in carnitine, and how can they help prevent deficiency?
4. What role does carnitine play in muscle metabolism and energy production?
5. How does the use of certain medications, like valproate, contribute to carnitine deficiency?


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1. What are the common symptoms associated with undernutrition in both children and adults?
2. What are the primary causes of undernutrition, and how do they vary by demographic factors?
3. How can dietary deficiencies contribute to the development of metabolic disorders?
4. What treatment options are available for individuals suffering from severe undernutrition?
5. How does undernutrition impact the immune system and overall health in affected individuals?


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1. What are the diagnostic methods for carnitine palmitoyltransferase deficiency in neonates and adults?
2. How can pregnant women determine if their fetus is at risk for carnitine palmitoyltransferase deficiency?
3. What dietary interventions are recommended for individuals with carnitine deficiency?
4. What are the potential causes of carnitine deficiency in adults?
5. What is the recommended dosage of L-carnitine for treating carnitine deficiency?


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1. How does consuming uncooked cornstarch at bedtime help prevent early morning hypoglycemia in patients with nutritional disorders?
2. What role do medium-chain triglycerides play in the dietary management of certain nutritional deficiencies?
3. Which symptoms might indicate a deficiency in essential fatty acids such as linoleic and linolenic acid?
4. What are the potential causes of early morning hypoglycemia in individuals with metabolic disorders?
5. How can dietary adjustments, such as the inclusion of uncooked cornstarch, be integrated into a treatment plan for obesity-related hypoglycemia?


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1. What dietary changes should be made for patients with a fatty acid oxidation disorder?
2. What are the common symptoms of essential fatty acid deficiency in infants?
3. How can essential fatty acid deficiency lead to growth retardation in children?
4. What are the potential health risks associated with a low-fat diet in patients with fatty acid oxidation disorders?
5. What treatments are effective for addressing essential fatty acid deficiency in infants?


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1. What are the common symptoms associated with vitamin D deficiency?
2. How can a dietary imbalance lead to metabolic disorders?
3. What are the potential causes of iron deficiency anemia in adults?
4. What dietary changes can help manage obesity effectively?
5. What treatments are available for individuals suffering from malnutrition?


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1. What are the physiological processes that are affected by a deficiency of essential fatty acids (EFAs)?
2. How does the dietary intake of linoleic and linolenic acid influence skin and cell membrane integrity?
3. What symptoms might indicate a deficiency in essential fatty acids?
4. What dietary changes can reverse a deficiency in essential fatty acids?
5. How are eicosapentaenoic acid and docosahexaenoic acid related to essential fatty acid intake?


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1. What dietary sources can help prevent essential fatty acid (EFA) deficiency in infants?
2. How does the fat composition of cow's milk compare to that of human milk in relation to EFA deficiency?
3. What are the clinical signs and symptoms associated with EFA deficiency in adults and infants?
4. How can total parenteral nutrition (TPN) contribute to EFA deficiency, and what measures are taken to prevent it?
5. What treatment options are available for individuals diagnosed with EFA deficiency?


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1. What are the common symptoms associated with undernutrition in adults?
2. What dietary deficiencies are most likely to contribute to undernutrition?
3. How can undernutrition impact the immune system and overall health?
4. What are the primary causes of undernutrition in children?
5. What nutritional interventions are recommended for treating undernutrition?


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1. What are some effective behavioral measures to encourage oral intake in patients with anorexia?
2. When is nutritional support indicated for patients with eating or absorption problems?
3. What types of nutritional support are available for undernourished patients?
4. How can the scheduling of meals impact the nutritional intake of patients?
5. Why might nutritional support be contraindicated for dying or severely demented patients?


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1. How can indirect calorimetry be utilized to accurately predict the nutritional requirements of critically ill patients?
2. What factors influence total energy expenditure (TEE) in individuals with different activity levels and metabolic stress?
3. How does undernutrition affect resting metabolic rate (RMR) and what implications does this have for treatment strategies?
4. What are the potential consequences of not adjusting nutritional requirements in patients experiencing metabolic stress from conditions such as infection or trauma?
5. How can healthcare providers estimate protein requirements for patients with varying degrees of metabolic demands?


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1. How does the Mifflin-St. Jeor equation differ from the Harris-Benedict equation in estimating resting metabolic rate (RMR) for individuals with obesity?  
2. What are the implications of inadequate protein intake on muscle mass and overall health in patients with nutritional disorders?  
3. How can the total energy expenditure (TEE) be adjusted for individuals recovering from critical illness compared to sedentary individuals?  
4. What dietary interventions can help address protein deficiencies in individuals suffering from malnutrition?  
5. How can understanding RMR and protein requirements aid in the management of metabolic disorders?  


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1. How do metabolic stress and kidney failure affect nutritional requirements in patients?
2. What dietary deficiencies are commonly associated with elderly patients?
3. What are the symptoms of vitamin and mineral imbalances in individuals with nutritional disorders?
4. How can obesity impact the management of nutritional disorders in patients?
5. What treatments are recommended for patients experiencing metabolic disorders related to dietary deficiencies?


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1. What are the common symptoms associated with vitamin D deficiency, and how can it be treated?
2. What dietary adjustments can help manage symptoms of metabolic syndrome?
3. What are the primary causes of iron deficiency anemia, and what nutritional strategies can be employed to prevent it?
4. How does obesity impact the risk of developing nutritional disorders, and what interventions can be effective in addressing this?
5. What are the signs of a vitamin B12 deficiency, and what dietary sources can help restore adequate levels?


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1. How can body mass index (BMI) be utilized to assess the response to nutritional support in patients with obesity?
2. What role does body composition analysis play in evaluating lean body mass in individuals with nutritional disorders?
3. How can nitrogen balance be measured and interpreted in patients receiving nutritional support?
4. What are the implications of muscle strength measurement in assessing the effectiveness of nutritional interventions?
5. How does indirect calorimetry contribute to understanding metabolic disorders related to nutritional deficiencies?


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1. How can nitrogen balance be used to assess nutritional adequacy in adults?
2. What are the typical nitrogen losses in the human body, and how can they be estimated?
3. What dietary strategies can improve nitrogen balance in undernourished patients?
4. How does protein intake correlate with nitrogen intake and overall nutrition status?
5. What role does response to skin antigens play in evaluating the effectiveness of nutritional support?


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1. How does muscle strength relate to lean body mass in individuals with nutritional disorders?
2. What dietary deficiencies might contribute to an impaired response to skin antigens?
3. What are the primary symptoms of nutritional disorders caused by vitamin and mineral imbalances?
4. How can obesity impact the body's ability to respond to skin antigens?
5. What treatment options are available for individuals experiencing symptoms related to muscle weakness due to nutritional deficiencies?


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1. How can hand-grip dynamometry be used to assess muscle strength in patients with nutritional disorders?
2. What role do acute-phase reactant serum proteins play in evaluating nutritional status in the presence of inflammation?
3. Under what circumstances is enteral tube nutrition recommended for patients with nutritional deficiencies?
4. How does the stimulation of the ulnar nerve help in the electrophysiological assessment of nutritional disorders?
5. What are the implications of low levels of prealbumin and transferrin in patients with acute nutritional issues?


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1. What are the advantages of enteral nutrition over parenteral nutrition for patients with gastrointestinal disorders?
2. In which specific cases is enteral nutrition recommended for individuals suffering from severe protein-energy undernutrition?
3. How does enteral nutrition help preserve the structure and function of the gastrointestinal tract in patients with prolonged anorexia?
4. What are the potential complications associated with parenteral nutrition that are less common with enteral nutrition?
5. What factors contribute to the lower cost of enteral nutrition compared to parenteral nutrition?


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1. What are the potential causes of coma or depressed sensorium in patients requiring nutritional support?
2. How does liver failure impact the nutritional needs and feeding options for affected patients?
3. In what scenarios is tube feeding recommended for patients with head or neck trauma?
4. What metabolic stresses are associated with critical illnesses like burns, and how can nutritional support help?
5. What are the indications for using a nasogastric or nasoenteric tube in patients with malabsorption disorders?


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1. What are the indications for using an orogastric tube in patients with nasal injuries or deformities?
2. How does a jejunostomy tube differ from a gastrostomy tube in terms of patient eligibility and contraindications?
3. What are the risks associated with using jejunostomy tubes compared to gastrostomy tubes?
4. Under what circumstances would a feeding tube need to be surgically placed rather than using endoscopic or radiologic methods?
5. What factors influence the choice of tube feeding method based on physician capabilities and patient preferences?


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1. What are the differences between open and laparoscopic techniques for treating nutritional disorders?  
2. What types of liquid formulas are commonly used in the management of patients with nutritional disorders?  
3. How do feeding modules differ from polymeric formulas in addressing dietary deficiencies?  
4. What specialized formulas are available for individuals with metabolic disorders?  
5. What are the potential health implications of vitamin and mineral imbalances in patients with obesity?  


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1. What are the advantages of using polymeric formulas over feeding modules for patients with nutritional deficiencies?  
2. How can lactose-intolerant patients manage their nutritional needs when using milk-based formulas?  
3. What types of patients would benefit from specialized formulas such as hydrolyzed protein or amino acid formulas?  
4. In what situations might feeding modules be preferred over complete polymeric formulas?  
5. What dietary considerations should be taken into account for hospitalized patients requiring tube feedings?  


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1. What are the recommended types of formulas for patients with pancreatic insufficiency?
2. How should patients be positioned during tube feeding to reduce the risk of aspiration pneumonia?
3. What are the benefits of using calorie- and protein-dense formulas for patients with fluid restrictions?
4. How do fiber-enriched formulas assist patients who experience constipation?
5. What are the feeding methods available for patients requiring tube feedings?


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1. What are the advantages of bolus feeding for patients with diabetes compared to continuous infusion?
2. How can nausea from bolus feeding impact the nutritional management of patients with diabetes?
3. What symptoms indicate that a patient may need to switch from bolus feeding to continuous infusion?
4. What factors should be considered when deciding on a feeding method for patients with diabetes?
5. How does the choice of feeding method affect the overall health outcomes of patients with nutritional disorders?


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1. What are the potential complications associated with enteral tube nutrition in patients receiving bolus feeding?
2. How does the method of bolus feeding impact the risk of gastrointestinal complications in patients?
3. What are the signs and symptoms that may indicate complications from enteral tube nutrition?
4. What dietary adjustments can be made to minimize complications during enteral feeding?
5. What factors should be considered when determining the total daily volume for bolus feeding in enteral nutrition?


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1. What are the common causes of diarrhea in patients receiving nasogastric or nasoduodenal tube feeding?
2. How should tube feeding formulas be adjusted for patients who initially experience gastrointestinal intolerance?
3. What precautions should be taken to prevent clogging in feeding tubes during nutritional support?
4. How does the caloric density of tube feeding formulas (0.5, 1, or 2 kcal/mL) affect patient tolerance and nutritional status?
5. What are the potential complications associated with nasogastric or nasoduodenal tube feeding in patients with nutritional disorders?


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1. How does the caloric concentration of a nutritional formula impact gastric emptying in patients with feeding difficulties?
2. What are the potential risks of using a 1-kcal/mL formula undiluted at a rate of 50 mL/h for patients recovering from illness?
3. In what situations should a more dilute formula be considered over a higher caloric concentration formula for patients with high gastric residuals?
4. What symptoms might indicate that a patient is experiencing decreased gastric emptying due to their nutritional formula?
5. How can adjusting the feeding rate or caloric concentration of a formula help manage symptoms in patients with metabolic disorders?


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1. What are the recommended initial feeding rates and concentrations for patients receiving jejunostomy tube feeding?
2. How can increased water loss due to vomiting, diarrhea, sweating, or fever affect nutritional treatment in patients?
3. What strategies can be employed to ensure adequate hydration in patients receiving tube feeding?
4. How does the dilution of tube feeding solutions vary based on the type of feeding tube used?
5. What are the potential complications associated with inadequate caloric and water intake in patients on tube feeding?


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1. What are the recommended caloric and volume adjustments for patients with specific nutritional disorders after a few days of treatment?
2. What is the maximum caloric concentration that can be tolerated in a nutritional therapy regimen?
3. What are the potential complications associated with high-calorie nutritional interventions?
4. How can a patient’s daily caloric needs be calculated based on their volume intake of nutritional solutions?
5. What symptoms may indicate that a patient is experiencing complications from nutritional therapy?


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1. What are the indications for using Total Parenteral Nutrition (TPN) in hospitalized patients?
2. How does Total Parenteral Nutrition differ from Partial Parenteral Nutrition in terms of nutritional support?
3. What are the potential complications associated with the use of TPN, particularly regarding venous access?
4. In what situations should parenteral nutrition not be routinely administered to patients?
5. What are the key components of a typical Total Parenteral Nutrition solution?


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1. What are the specific indications for using Total Parenteral Nutrition (TPN) in patients with gastrointestinal disorders?
2. How does TPN compare to enteral nutrition in terms of complications and preservation of GI tract function?
3. What are the recommended daily fluid and energy requirements for patients receiving TPN?
4. What types of gastrointestinal disorders may necessitate complete bowel rest and the use of TPN?
5. What are the potential nutritional deficiencies that can arise from prolonged use of TPN?


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1. What are the recommended daily dextrose requirements for patients with hypermetabolism?
2. How do underlying disorders influence the nutritional support solutions for patients?
3. What are the potential consequences of a carbohydrate-heavy diet in individuals with specific nutritional disorders?
4. How can laboratory results affect the formulation of nutritional solutions for patients with dietary deficiencies?
5. What role do vitamin and mineral imbalances play in the management of obesity-related health conditions?


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1. How do lipid emulsions contribute to the caloric needs of patients with nutritional disorders?
2. What role do essential fatty acids play in the management of metabolic needs in individuals with obesity?
3. How might withholding lipids from a patient's diet affect their insulin sensitivity?
4. What are the potential benefits of using lipid emulsions in patients with specific dietary deficiencies?
5. In what situations might it be appropriate to restrict lipids in the diet of obese patients?


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1. What dietary considerations should be made for patients with renal insufficiency not receiving dialysis?
2. How does the nutritional management differ for patients with heart failure compared to those with liver failure?
3. What type of lipid emulsion is recommended for patients experiencing respiratory failure, and why?
4. What are the recommended dextrose concentrations for neonates receiving total parenteral nutrition (TPN)?
5. What protocols should be followed to ensure the safe administration of TPN through a central venous catheter?


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1. What are the signs and symptoms of infection that patients receiving TPN at home should be taught to recognize?  
2. How often should the external tubing for TPN be changed to prevent complications?  
3. What is the recommended starting dose of regular insulin to be added to TPN fluid when the plasma glucose level is normal?  
4. How should energy and nitrogen be administered in relation to TPN solutions?  
5. What sterile techniques should be followed when changing dressings for TPN to minimize infection risk?  


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1. What specific blood tests should be monitored for patients with nutritional disorders, and how frequently should they be conducted?
2. How does monitoring plasma glucose levels every 6 hours help in the management of patients with nutritional disorders?
3. Why is it important to assess liver function tests in patients with nutritional disorders?
4. What do changes in transthyretin and retinol-binding protein indicate about a patient's clinical status?
5. How can continuous monitoring of fluid intake and output benefit patients with nutritional disorders?


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1. What are the key anthropometric measurements used to assess nutritional disorders?
2. How frequently should a full nutritional assessment be conducted for individuals at risk of metabolic disorders?
3. What symptoms might indicate a deficiency in essential vitamins or minerals?
4. What are some common causes of obesity that can be identified through a nutritional assessment?
5. What treatment options are available for individuals diagnosed with dietary deficiencies?


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1. What are the potential complications associated with central venous access in patients with nutritional disorders?
2. How do vitamin and mineral imbalances contribute to the development of nutritional disorders?
3. What symptoms are commonly observed in patients experiencing dietary deficiencies?
4. What treatment options are available for patients suffering from metabolic disorders related to nutrition?
5. How can obesity influence the risk of developing complications from nutritional disorders?


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1. What are the common symptoms associated with glucose abnormalities in patients receiving total parenteral nutrition?
2. How does catheter-related sepsis impact the overall health of patients on total parenteral nutrition?
3. What dietary deficiencies are most likely to occur in patients experiencing liver dysfunction due to total parenteral nutrition?
4. What are the recommended treatments for managing hyperglycemia in patients on total parenteral nutrition?
5. What are the potential causes of metabolic disorders in individuals receiving total parenteral nutrition?


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1. What are the potential causes of hyperglycemia in patients receiving TPN (total parenteral nutrition)?
2. How can hypoglycemia be treated in patients experiencing low blood sugar levels during TPN therapy?
3. What monitoring practices are recommended to prevent glucose abnormalities in patients receiving nutritional support?
4. What are the signs and symptoms of hypoglycemia that caregivers should be aware of?
5. How does the abrupt cessation of concentrated dextrose infusions contribute to hypoglycemia?


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1. What are the common hepatic complications associated with total parenteral nutrition (TPN) in infants?
2. How does liver dysfunction manifest in patients receiving TPN, and what laboratory values indicate this condition?
3. What factors contribute to the development of hyperammonemia in patients on TPN?
4. In what ways can excess amino acids during TPN treatment lead to persistent liver dysfunction?
5. Why are premature infants at a higher risk for developing hepatic complications when undergoing TPN?


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1. What role does cholestasis play in the pathogenesis of the nutritional disorder described in the document?  
2. How can arginine supplementation help in managing hyperammonemia in infants?  
3. What dietary modifications are recommended for infants with hepatomegaly due to fat accumulation?  
4. What are the signs of hyperammonemia in infants, and how can it be identified early?  
5. How should abnormalities in serum electrolytes and minerals be addressed in the context of this nutritional disorder?  


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1. What are the potential consequences of prolonged total parenteral nutrition (TPN) usage on bone health?
2. How can dehydration be effectively managed in patients receiving nutritional support?
3. What are the signs of volume overload in patients with high daily energy requirements?
4. What nutritional deficiencies are most commonly associated with long-term TPN therapy?
5. How can the risk of osteoporosis and osteomalacia be mitigated in patients undergoing TPN for extended periods?


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1. What are the potential adverse reactions to lipid emulsions in patients receiving TPN, and how can they be managed?  
2. How does stopping TPN affect severe periarticular and lower-extremity pain in advanced nutritional disorders?  
3. What dietary modifications can help prevent gallbladder complications in patients on long-term TPN?  
4. What are the signs of delayed adverse reactions to lipid emulsions, and who is most at risk for these complications?  
5. How can temporary hyperlipidemia in patients with kidney or liver failure be addressed in the context of TPN?  


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1. What are the common symptoms associated with vitamin D deficiency?
2. How can enteral nutrition support individuals with metabolic disorders?
3. What dietary changes can help manage obesity-related health issues?
4. What causes iron deficiency anemia, and how can it be treated?
5. What role do oral supplements play in correcting vitamin B12 deficiencies?


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1. What treatments are available for patients suffering from cholestasis and how do they impact nutritional status?
2. How does anorexia affect the nutritional needs of dying patients?
3. What role do dietary deficiencies play in the progression of cholestasis?
4. How can nutritional support be effectively implemented for severely demented patients experiencing loss of appetite?
5. What are the common symptoms associated with nutritional disorders in patients with cholestasis?


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1. What are the common symptoms associated with vitamin D deficiency?
2. How can a person manage iron-deficiency anemia through dietary changes?
3. What are the primary causes of obesity in adults, and how can they be addressed?
4. Which metabolic disorders are commonly linked to dietary deficiencies, and what are their implications?
5. What treatments are available for individuals suffering from vitamin B12 deficiency?


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1. What behavioral measures can be implemented to increase oral intake in patients with nutritional disorders?
2. How do certain medications, like megestrol acetate and dronabinol, stimulate appetite in individuals with nutritional deficiencies?
3. What role does metoclopramide play in the management of nutritional disorders, and how long does it take to reach peak effectiveness?
4. In patients with advanced dementia, what are the considerations for providing tube feedings when they can no longer eat?
5. How can small portions of favorite or strongly flavored foods impact the dietary intake of individuals with eating difficulties?


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1. What are the potential complications associated with tube feedings in patients with nutritional disorders?
2. How does parenteral nutrition impact the comfort and quality of life for individuals with severe dietary deficiencies?
3. What evidence exists regarding the effectiveness of tube feedings in preventing aspiration and pressure ulcers in patients?
4. In what scenarios are tube feedings considered inappropriate for patients with metabolic disorders?
5. What alternative nutritional support options are available for patients who experience discomfort from tube feedings?


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1. What are the potential signs that a patient is unable to eat or drink adequately due to a nutritional disorder?
2. How can family members provide supportive care to patients who are experiencing difficulties with eating?
3. What non-invasive nutritional support options are available for patients who prefer not to undergo invasive procedures?
4. What role does good oral hygiene play in the comfort of patients with nutritional disorders?
5. How can counseling help family members cope with the decision-making process regarding nutritional support for their loved ones?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency, and how can they be managed?
2. What dietary changes can help address iron deficiency anemia in adults?
3. What are the primary causes of obesity, and what nutritional interventions are recommended for weight management?
4. How can metabolic disorders impact nutrient absorption, and what treatments are available to improve this?
5. What are the recommended dietary sources of essential fatty acids, and how do deficiencies affect overall health?


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1. What are the symptoms associated with a deficiency in vitamin B12, and how can it be treated?
2. How does vitamin D deficiency affect overall health, and what dietary sources can help prevent it?
3. What are the potential toxic effects of excessive vitamin A intake, and what are the recommended dosage guidelines to avoid toxicity?
4. In what ways can folate deficiency impact pregnant women and fetal development?
5. What are the dietary sources of water-soluble vitamins, and how can deficiencies in these vitamins be addressed?


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1. What is the difference between Recommended Daily Allowance (RDA) and Adequate Intake (AI) for vitamins?
2. How can a Tolerable Upper Intake Level (UL) help prevent adverse health effects related to vitamin consumption?
3. What are the potential causes of vitamin deficiencies in developed countries?
4. What symptoms might indicate a deficiency in essential vitamins or nutrients?
5. How can dietary adjustments help treat specific nutritional disorders linked to vitamin imbalances?


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1. What are the common symptoms of vitamin deficiency in frail and institutionalized elderly individuals?
2. How can alcoholism contribute to nutritional disorders?
3. What are the potential health impacts of prolonged and inadequately supplemented parenteral feeding?
4. What nutritional deficiencies are most prevalent in developing countries, and what are their causes?
5. How can protein-energy undernutrition affect the overall health of elderly people?


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1. What are the symptoms associated with deficiencies of water-soluble vitamins?
2. How long does it typically take for deficiencies of fat-soluble vitamins to develop in the body?
3. What genetic defects can lead to vitamin dependency and how can high doses of vitamins improve metabolic function in these cases?
4. What are the potential health risks associated with hypervitaminosis from megadoses of vitamins A, D, C, B6, or niacin?
5. How can irregular eating patterns contribute to suboptimal vitamin intake and what strategies can be implemented to address this issue?


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1. What nutritional deficiencies are associated with an increased risk of certain types of cancer?
2. How can metabolic disorders impact an individual's overall nutritional status?
3. What symptoms should prompt an individual to seek evaluation for a potential dietary deficiency?
4. What dietary changes can help mitigate the effects of obesity-related health conditions?
5. Which vitamins and minerals are most commonly imbalanced in individuals with nutritional disorders?


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1. What are the recommended daily intakes for biotin and pantothenic acid for adults, and what are the potential consequences of deficiencies in these vitamins?
2. How does the bioavailability of folate differ between supplements and natural food sources, and what implications does this have for individuals at risk of deficiency?
3. What role do multivitamin supplements play in preventing nutritional disorders associated with inadequate intake of biotin and pantothenic acid?
4. Are there any proven benefits of pantothenic acid supplementation for improving lipid metabolism or athletic performance?
5. What are the dietary sources of folate, and how does the fortification of grain foods in the US impact overall folate intake in the population?


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1. What are the common symptoms associated with vitamin D deficiency, and how can they affect overall health?
2. What dietary changes can help manage obesity and its related health conditions?
3. What are the primary causes of iron-deficiency anemia, and what treatment options are available?
4. How do metabolic disorders impact nutrient absorption and overall health?
5. What are the potential health risks associated with a deficiency in vitamin B12, and what foods can help prevent it?


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1. What are the common symptoms associated with vitamin deficiencies in adults?
2. How can vitamin toxicity impact overall health and what are the signs to look for?
3. What dietary changes can help address vitamin deficiencies and improve nutritional status?
4. What are the potential causes of vitamin dependency in individuals?
5. How do metabolic disorders affect the body's ability to utilize vitamins and minerals effectively?


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1. What role do folates play in the maturation of red blood cells and the synthesis of nucleotides?  
2. How does a deficiency in folate affect fetal nervous system development?  
3. What are the potential symptoms associated with folate deficiency in adults?  
4. Which dietary sources are rich in folate, and how can individuals ensure adequate intake?  
5. What treatments or interventions are recommended for individuals diagnosed with folate deficiency?  


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1. What is the role of folate in reducing the risk of various cancers?
2. How does folate supplementation affect homocysteine levels and cardiovascular health?
3. What are the recommended dosages of folate for women who have had a baby with a neural tube defect?
4. Are there any potential toxic effects associated with excessive folate intake?
5. What dietary sources are rich in folate, and how can deficiencies be addressed?


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1. What are the common causes of folate deficiency in individuals?
2. How does folate deficiency contribute to megaloblastic anemia?
3. What are the potential health risks associated with maternal folate deficiency during pregnancy?
4. What dietary sources are rich in folate to help prevent deficiency?
5. What treatments are available for individuals diagnosed with folate deficiency?


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1. What laboratory tests are used to diagnose neutrophil hypersegmentation in nutritional disorders?  
2. What symptoms are associated with folate deficiency and neutrophil hypersegmentation?  
3. How effective is oral folate treatment for individuals diagnosed with neutrophil hypersegmentation?  
4. What are the potential causes of neutrophil hypersegmentation in patients?  
5. Are there dietary changes that can help prevent folate deficiency and its related symptoms?  


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1. What are the primary causes of folate deficiency in patients with undernutrition or alcoholism?
2. How does alcohol consumption affect the absorption and metabolism of folate?
3. What role does prolonged cooking play in the bioavailability of folate in food?
4. Which medications are known to impair folate metabolism and potentially lead to deficiency?
5. How does the enrichment of dietary staples with folate in the US help reduce the risk of deficiency?


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1. What are the common symptoms associated with folate deficiency?
2. How can folate deficiency lead to anemia, and what are the compensatory mechanisms involved?
3. What dietary sources are rich in folate to help prevent deficiency?
4. What type of treatments are available for individuals diagnosed with folate deficiency?
5. How does folate deficiency contribute to mental health issues such as depression and confusion?


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1. What are the potential risks associated with folate deficiency during pregnancy?
2. How can megaloblastic anemia be differentiated from vitamin B12 deficiency based on diagnostic tests?
3. What serum folate levels indicate a likely deficiency in pregnant women?
4. What are the common symptoms of folate deficiency in pregnant individuals?
5. What dietary sources can help prevent folate deficiency during pregnancy?


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1. What does a serum folate level of < 140 μg/L indicate about a person's nutritional status?
2. How can changes in dietary folate intake affect serum and erythrocyte folate levels?
3. What is the significance of elevated homocysteine levels in relation to tissue folate deficiency?
4. What are the potential health consequences of inadequate folate status in the body?
5. How can one improve their folate levels through dietary choices?


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1. What are the potential symptoms of vitamin B12 deficiency, and how can they be differentiated from folate deficiency?
2. How do methylmalonic acid (MMA) levels help in diagnosing vitamin B12 deficiency compared to folate deficiency?
3. What dietary sources can help replenish folate levels in individuals with a deficiency?
4. What role do renal insufficiency and genetic factors play in the development of vitamin B12 and vitamin B6 deficiencies?
5. What is the recommended dosage of supplemental oral folate for treating folate deficiency?


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1. What are the symptoms of a deficiency in the nutrient that has a normal requirement of 400 μg/day?
2. What nutritional disorders are associated with a daily intake below 400 μg of this nutrient?
3. What are the potential long-term health effects of consistently consuming less than 400 μg/day of this nutrient?
4. How can dietary sources be adjusted to meet the recommended intake of 400 μg/day for this nutrient?
5. What treatments are available for individuals diagnosed with a deficiency of this nutrient that normally requires 400 μg/day?


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1. What are the potential causes of folate deficiency in patients with megaloblastic anemia?
2. How does vitamin B12 deficiency interact with folate supplementation in the treatment of megaloblastic anemia?
3. What is the recommended daily allowance of folate for pregnant women, and how does it differ for those with a history of neural tube defects?
4. What are the consequences of treating folate deficiency without first ruling out vitamin B12 deficiency?
5. How can folate supplementation impact neurological health in patients with vitamin B12 deficiency?


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1. What are the symptoms of niacin deficiency in individuals?
2. How can niacin deficiency be treated through dietary changes?
3. What metabolic disorders are associated with an imbalance of niacin in the body?
4. What are the potential health consequences of excessive niacin intake?
5. How does niacin contribute to energy metabolism and overall health?


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1. What are the clinical manifestations of niacin deficiency and how do they present in patients?
2. How can dietary sources of tryptophan help compensate for inadequate niacin intake?
3. What are the primary causes of dietary niacin deficiency in populations that rely heavily on maize in their diet?
4. How is niacin deficiency diagnosed in individuals presenting with symptoms such as dermatitis and cognitive decline?
5. What treatment options are available for patients diagnosed with niacin deficiency or pellagra?


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1. What are the potential causes of secondary deficiency in nutritional disorders?
2. How does carcinoid syndrome contribute to the development of pellagra?
3. What are the common symptoms associated with advanced pellagra?
4. In what ways does Hartnup disease affect the absorption of tryptophan?
5. What are the characteristic signs of gastrointestinal involvement in pellagra?


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1. What are the characteristic skin lesions associated with vitamin deficiencies, and how can their distribution help in diagnosis?
2. How do pressure points and sun-exposed areas relate to the manifestation of skin symptoms in nutritional disorders?
3. What is the clinical significance of the "pellagrous glove" distribution of lesions in diagnosing nutritional deficiencies?
4. What nutritional deficiencies are commonly linked to bilaterally symmetric skin lesions?
5. What treatment options are available for skin symptoms resulting from vitamin deficiencies?


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1. What are the primary symptoms associated with pellagra, and how do they manifest on the skin?
2. How does exposure to sunlight exacerbate the symptoms of Casal's necklace in individuals with nutritional deficiencies?
3. What mucous membrane symptoms are commonly observed in nutritional disorders, particularly in relation to the mouth and genital areas?
4. What dietary deficiencies are linked to the development of butterfly-shaped lesions on the face?
5. What treatment options are available for individuals experiencing symptoms of nutritional disorders such as those described in the document?


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1. What are the primary symptoms associated with acute deficiency that can lead to glossitis and stomatitis?  
2. How does the progression of a nutritional deficiency affect the appearance and health of the tongue and oral mucous membranes?  
3. What gastrointestinal symptoms might indicate the early stages of a nutritional deficiency?  
4. What dietary changes can help alleviate the symptoms of glossitis and stomatitis related to nutritional deficiencies?  
5. What are the potential long-term consequences of untreated nutritional deficiencies on oral health?  


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1. What are the common symptoms associated with nutritional disorders that may include nausea, vomiting, and diarrhea?
2. What nutritional deficiencies could lead to symptoms such as nausea, vomiting, and diarrhea?
3. What are the potential causes of nausea, vomiting, and diarrhea in individuals with metabolic disorders?
4. How can dietary changes help alleviate nausea, vomiting, and diarrhea caused by nutritional imbalances?
5. What treatments are recommended for managing nausea, vomiting, and diarrhea in patients with obesity-related nutritional disorders?


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1. What are the potential causes of diarrhea that presents with bloody stools and associated CNS symptoms?
2. How can cognitive decline, such as dementia, be linked to nutritional deficiencies in individuals experiencing diarrhea?
3. What clinical evaluations are necessary to diagnose a nutritional disorder characterized by skin lesions, diarrhea, and cognitive symptoms?
4. What treatment options are available for individuals suffering from psychosis related to severe nutritional deficiencies?
5. How can dietary changes help alleviate symptoms of bowel hyperemia and ulceration associated with nutritional disorders?


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1. What are the primary symptoms associated with niacin deficiency, and how can they be distinguished from other nutritional disorders?  
2. How does a diet lacking in tryptophan contribute to the development of niacin deficiency?  
3. What is the role of niacin in the central nervous system, and what changes may occur due to its deficiency?  
4. How can a favorable response to niacin treatment be used to confirm a diagnosis of niacin deficiency?  
5. What dietary changes can be recommended to prevent niacin and tryptophan deficiencies?  


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1. What laboratory tests can help confirm a diagnosis of niacin deficiency, and what specific urinary excretion levels indicate this deficiency?  
2. What are the recommended treatment options for niacin deficiency, and how do they differ from those for niacin toxicity?  
3. What symptoms are associated with niacin toxicity, and how can these symptoms be minimized during treatment?  
4. How does the dosage of nicotinamide for treating deficiency compare to the dosage of niacin used for managing lipid levels?  
5. What precautions should be taken when administering high doses of niacin, particularly in patients with preexisting health conditions?  


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1. How can sustained-release medications contribute to hepatotoxicity in individuals with nutritional disorders?
2. What are the symptoms of hepatotoxicity that may arise from dietary deficiencies?
3. What dietary factors could increase the risk of hepatotoxicity in patients with metabolic disorders?
4. How can the treatment of nutritional disorders be adjusted to minimize the risk of hepatotoxicity from medications?
5. What vitamin and mineral imbalances are associated with an increased risk of liver toxicity in patients on sustained-release preparations?


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1. What are the common symptoms of vitamin D deficiency, and how can they be managed?
2. What dietary sources are recommended to prevent vitamin B12 deficiency in vegetarians?
3. How does iron deficiency anemia develop, and what treatments are available to restore iron levels?
4. What are the potential health risks associated with excessive vitamin A intake?
5. How can obesity be addressed through dietary changes and nutritional interventions?


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1. What are the potential symptoms of riboflavin deficiency and how can they be identified?
2. How does niacin affect serum glucose levels in individuals with metabolic disorders?
3. What are the recommended dietary sources of riboflavin to prevent deficiency?
4. How often should levels of uric acid and plasma transaminases be monitored when starting niacin treatment?
5. What role does riboflavin play in carbohydrate metabolism and how can its deficiency impact overall health?


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1. What are the potential symptoms of riboflavin deficiency in individuals?
2. How can riboflavin deficiency be diagnosed and treated effectively?
3. What dietary sources are rich in riboflavin to prevent deficiency?
4. Are there any known metabolic disorders associated with riboflavin imbalances?
5. How does riboflavin toxicity compare to its deficiency in terms of health effects?


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1. What are the common symptoms associated with riboflavin deficiency?
2. What dietary sources can help prevent primary riboflavin deficiency?
3. What are the potential causes of secondary riboflavin deficiency?
4. How is riboflavin deficiency diagnosed and treated?
5. What are the skin manifestations of riboflavin deficiency?


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1. What are the characteristic symptoms of riboflavin deficiency, and how do they manifest in patients?
2. How can riboflavin deficiency be diagnosed in individuals with other B vitamin deficiencies?
3. What is the recommended daily dosage of riboflavin for treatment of deficiency, and how long should it be administered?
4. What laboratory tests are used to confirm riboflavin deficiency in patients?
5. What other vitamins should be administered alongside riboflavin during treatment for deficiency?


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1. What are the common dietary sources of thiamin, and how can a lack of these sources lead to deficiency?  
2. What symptoms are associated with thiamin deficiency, and how can they impact an individual's health?  
3. How does a diet high in refined carbohydrates contribute to thiamin deficiency and its related disorders?  
4. In what ways can thiamin be utilized in the diagnosis and treatment of beriberi and Wernicke-Korsakoff syndrome?  
5. What populations are at the highest risk for developing thiamin deficiency, and what preventive measures can be taken?


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1. What are the common symptoms associated with vitamin D deficiency?
2. How can a person effectively manage obesity through dietary changes?
3. What are the primary causes of iron deficiency anemia and how can it be treated?
4. What role do B vitamins play in metabolism, and what are the potential consequences of their deficiency?
5. What dietary modifications can help alleviate the symptoms of metabolic syndrome?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency?
2. How can a vitamin B12 deficiency impact neurological function?
3. What dietary changes can help prevent iron deficiency anemia?
4. What are the potential health risks of excessive vitamin A intake?
5. How does obesity influence the metabolism of certain vitamins and minerals?


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1. What are the primary causes of secondary thiamin deficiency?
2. How does prolonged diarrhea contribute to impaired absorption of thiamin?
3. What are the neurological symptoms associated with thiamin deficiency?
4. In what ways does alcohol consumption affect thiamin metabolism and absorption?
5. What are the potential health implications of thiamin deficiency during pregnancy and breastfeeding?


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1. What are the common symptoms associated with dilated heart conditions due to nutritional disorders?
2. How can nutritional deficiencies lead to high-output heart failure?
3. What dietary changes can help prevent the swelling and edema in the feet and legs caused by nutritional disorders?
4. What role do vitamins and minerals play in maintaining heart muscle health and preventing fragmentation of muscle fibers?
5. How can arteriovenous shunting of blood be influenced by nutritional imbalances in the body?


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1. What are the early symptoms associated with thiamin deficiency?
2. How does dry beriberi manifest in individuals with thiamin deficiency?
3. What are the potential neurological effects of a thiamin deficiency?
4. What lifestyle changes can help alleviate symptoms of thiamin deficiency?
5. How can one differentiate between general fatigue and symptoms specifically related to thiamin deficiency?


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1. What are the early signs of polyneuropathy associated with nutritional deficiencies?
2. How can muscle cramps and calf tenderness indicate a specific nutritional disorder?
3. What dietary deficiencies are commonly linked to symptoms like burning feet and paresthesias?
4. What is the relationship between Wernicke-Korsakoff syndrome and nutritional deficiencies?
5. How does continued deficiency in certain nutrients lead to worsening symptoms in the lower extremities?


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1. What are the primary symptoms of Wernicke's encephalopathy associated with thiamin deficiency?
2. How does Korsakoff's psychosis develop after episodes of Wernicke's encephalopathy?
3. What are the cardiovascular effects of thiamin deficiency that lead to wet beriberi?
4. What dietary factors contribute to the development of thiamin deficiency in alcoholics?
5. How can thiamin deficiency be treated to prevent the progression of Wernicke's encephalopathy and Korsakoff's psychosis?


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1. What nutritional deficiencies can contribute to the development of heart failure symptoms such as orthopnea and edema?
2. How do dietary imbalances affect the progression of heart failure and related symptoms?
3. What are the nutritional recommendations for managing edema in patients with heart failure?
4. Which vitamins and minerals are critical for preventing heart failure and its associated symptoms?
5. How can obesity influence the risk of developing heart failure and its related complications?


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1. What are the symptoms of infantile beriberi in breastfed infants with thiamin deficiency?
2. How can a favorable response to thiamin treatment aid in diagnosing thiamin deficiency?
3. What risks are associated with glucose infusions in individuals with thiamin deficiency?
4. What differentiates thiamin deficiency-related polyneuropathies from those caused by diabetes or vitamin B12 deficiency?
5. What are the potential consequences of thiamin deficiency if left untreated?


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1. What are the common symptoms and causes of vitamin D deficiency?
2. How can a severe vitamin B12 deficiency impact overall health?
3. What dietary changes can help alleviate symptoms of iron deficiency anemia?
4. What are the potential health risks associated with excessive vitamin A intake?
5. How can nutritional deficiencies lead to metabolic disorders in adults?


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1. What are the symptoms of cardiovascular beriberi and how can they be differentiated from other heart failure disorders?
2. How can measuring electrolytes, including magnesium, help in diagnosing nutritional disorders?
3. What role does erythrocyte transketolase activity play in confirming thiamin deficiency?
4. What therapeutic trial can be conducted to determine if thiamin supplementation is effective in treating cardiovascular beriberi?
5. What other nutritional deficiencies should be considered when diagnosing a patient with symptoms of heart failure?


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1. What are the recommended thiamin dosages for patients with mild and moderate polyneuropathy?
2. How does intravenous glucose administration affect patients with thiamin deficiency?
3. What are the treatment options for Wernicke-Korsakoff syndrome and how long should they be administered?
4. What dietary recommendations should be followed to prevent thiamin deficiency in at-risk individuals?
5. How can the symptoms of ophthalmoplegia related to thiamin deficiency be expected to resolve over time?


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1. What are the symptoms of Vitamin A deficiency and how do they affect vision?
2. What are the potential causes of Vitamin A deficiency in individuals?
3. How can Vitamin A deficiency impact epithelial tissue health?
4. What dietary sources are rich in Vitamin A to prevent deficiency?
5. What treatments are available for individuals diagnosed with Vitamin A deficiency?


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1. What are the symptoms of vitamin A deficiency and how can they be identified?
2. How does the body process provitamin A carotenoids compared to preformed vitamin A?
3. What dietary sources are most effective for increasing vitamin A levels in the body?
4. How do cooking methods affect the absorption of carotenoids from vegetables?
5. What role do synthetic vitamin analogs (retinoids) play in the treatment of skin disorders related to vitamin A?


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1. What are the potential health risks associated with β-carotene supplementation in relation to cancer risk?
2. How can liver disorders contribute to vitamin A deficiency in individuals?
3. What are the symptoms of vitamin A deficiency, and how can they be identified?
4. What dietary changes can help prevent vitamin A deficiency and its associated health risks?
5. In what ways can fat malabsorption lead to nutritional deficiencies, specifically regarding vitamin A?


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1. What are the symptoms associated with vitamin A deficiency, and how do they affect the immune system and hematopoiesis?
2. How is vitamin A deficiency diagnosed, and what specific ocular findings are indicative of this condition?
3. What are the primary causes of vitamin A deficiency in populations that rely on rice as a staple food?
4. What treatment options are available for individuals with severe vitamin A deficiency, particularly in cases of malabsorption?
5. In which geographic regions is vitamin A deficiency most commonly found, and what dietary factors contribute to its prevalence?


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1. What are the primary causes of xerophthalmia in young children, particularly in developing countries?
2. How does a deficiency in vitamin A lead to the development of xerophthalmia?
3. What are the common symptoms associated with xerophthalmia in affected individuals?
4. What treatment options are available for children diagnosed with xerophthalmia due to nutritional deficiencies?
5. How can the incidence of xerophthalmia be reduced in populations at risk for vitamin A deficiency?


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1. What are the common symptoms associated with vitamin deficiencies and how can they be identified?  
2. What dietary changes can help prevent vitamin or mineral deficiencies?  
3. How does vitamin toxicity occur, and what are the potential health risks associated with it?  
4. What metabolic disorders are linked to specific vitamin deficiencies, and what treatments are available?  
5. How can obesity impact the absorption of vitamins and minerals in the body?  


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1. What are the common causes of secondary vitamin A deficiency?
2. How does chronic diarrhea contribute to the risk of vitamin A deficiency?
3. What symptoms are associated with impaired dark adaptation due to vitamin A deficiency?
4. In what ways can vitamin A supplementation impact children with complicated measles?
5. How does protein-energy undernutrition affect vitamin A storage and transport in the body?


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1. What are the primary symptoms of xerophthalmia and how do they progress with advanced deficiency?
2. How does a deficiency in vitamin A lead to the development of Bitot's spots in the eyes?
3. What are the potential consequences of untreated keratomalacia associated with xerophthalmia?
4. What dietary changes can help prevent the occurrence of xerophthalmia and its associated symptoms?
5. In what ways can keratinization affect other mucous membranes in the body beyond the eyes?


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1. What nutritional deficiencies could lead to drying, scaling, and follicular thickening of the skin?  
2. How can respiratory infections be linked to metabolic disorders or nutritional deficiencies?  
3. What dietary changes can help alleviate symptoms associated with skin scaling and dryness?  
4. Which vitamins or minerals are essential for maintaining healthy skin and preventing dryness?  
5. What treatment options are available for individuals experiencing skin scaling and respiratory issues due to nutritional imbalances?  


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1. What are the common symptoms of vitamin A deficiency in children?
2. How can vitamin A deficiency be diagnosed and what tests are involved?
3. What are the potential consequences of untreated vitamin A deficiency in young patients?
4. How does vitamin A deficiency impact the immune system, particularly in children?
5. What therapeutic interventions are available for treating vitamin A deficiency?


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1. What dietary changes can help prevent vitamin A deficiency?
2. Which food sources are rich in vitamin A and can be included in a balanced diet?
3. What are the symptoms associated with a lack of vitamin A in the diet?
4. How can incorporating dark green leafy vegetables benefit overall nutritional health?
5. What role do fortified foods play in preventing nutritional disorders?


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1. How can the absorption of carotenoids be enhanced in the diet?
2. What are the recommended vitamin A dosages for infants and children in developing countries?
3. What are the symptoms and treatment options for vitamin A deficiency?
4. How should dietary deficiencies in vitamin A be addressed in infants with a suspected milk allergy?
5. What is the protocol for treating vitamin A deficiency in cases of vomiting or malabsorption?


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1. What are the common symptoms associated with vitamin D deficiency, and how can it be diagnosed?
2. How can a vitamin B12 deficiency impact mental health and cognitive function?
3. What dietary changes can be made to prevent iron deficiency anemia?
4. What are the potential health risks of excessive vitamin A intake, and how can it be managed?
5. How does a lack of essential fatty acids contribute to metabolic disorders, and what dietary sources can help mitigate this deficiency?


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1. What are the recommended vitamin A dosages for infants and children with complicated measles?
2. What are the potential symptoms of acute and chronic vitamin A toxicity?
3. How should infants born to HIV-positive mothers be treated with vitamin A?
4. What are the risks associated with prolonged daily administration of large doses of vitamin A to infants?
5. What are the recommended daily limits of vitamin A for pregnant or breastfeeding women to avoid toxicity?


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1. What are the symptoms of acute vitamin A toxicity in children, and how can it occur?
2. How does chronic vitamin A toxicity develop in adults, and what are the potential long-term effects?
3. What dietary sources can lead to acute vitamin A toxicity, particularly in arctic explorers?
4. What are the risks associated with megavitamin therapy and excessive vitamin A intake for skin disorders?
5. How does excessive carotene ingestion differ from vitamin A toxicity in terms of symptoms and health effects?


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1. What are the symptoms and signs associated with carotenemia and carotenodermia?
2. How does the intake of β-carotene supplements compare to consuming carotenoids through fruits and vegetables in terms of cancer risk?
3. What are the potential health risks associated with acute or chronic toxicity of carotenoids?
4. What dietary sources are high in carotenoids that may help prevent carotenemia?
5. What treatments or dietary adjustments can be recommended for someone experiencing symptoms of carotenemia?


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1. What are the early symptoms of acute nutritional toxicity and how do they differ from chronic toxicity symptoms?
2. How does increased intracranial pressure relate to nutritional disorders?
3. What dietary changes can help alleviate symptoms of chronic toxicity such as coarse hair and dry skin?
4. What are the potential long-term health consequences of untreated nutritional disorders leading to symptoms like severe headaches and generalized weakness?
5. What treatments are recommended for individuals experiencing drowsiness and irritability due to acute toxicity from nutritional imbalances?


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1. What are the potential symptoms of cortical hyperostosis in children?
2. How does toxicity from nutritional disorders manifest in pediatric patients?
3. What are the risk factors for fractures in the elderly related to nutritional disorders?
4. What dietary deficiencies could lead to symptoms like pruritus and failure to thrive in children?
5. What treatments are available for managing arthralgia associated with nutritional disorders?


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1. What are the common symptoms associated with carotenodermia and how can it be differentiated from jaundice?
2. What clinical evaluations are typically conducted to diagnose hepatomegaly and splenomegaly?
3. What dietary factors can lead to carotenodermia and how can it be managed?
4. How do hepatomegaly and splenomegaly relate to underlying nutritional disorders?
5. What lifestyle changes can help prevent the development of nutritional disorders associated with vitamin and mineral imbalances?


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1. How do blood vitamin levels influence the risk of developing toxicity in patients with nutritional disorders?
2. What are the symptoms associated with vitamin deficiencies that may not correlate with blood vitamin levels?
3. What causes poor correlation between blood vitamin levels and toxicity in individuals with metabolic disorders?
4. What dietary changes can help address vitamin imbalances that are not reflected in blood tests?
5. How can healthcare providers better assess the risk of toxicity in patients with nutritional deficiencies despite normal blood vitamin levels?


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1. What laboratory tests are used to diagnose vitamin A toxicity, and what are the expected serum retinol levels?
2. What symptoms are associated with hypercalcemia in cases of vitamin A toxicity?
3. How can fasting serum retinol levels help differentiate between normal and toxic levels of vitamin A?
4. What are the potential health risks of prolonged vitamin A toxicity?
5. What dietary changes can help prevent vitamin A toxicity and maintain healthy serum retinol levels?


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1. What are the common symptoms associated with vitamin D deficiency, and how can they be identified?
2. What are the potential causes of vitamin B12 dependency, and how does it affect metabolism?
3. How can dietary deficiencies in iron lead to anemia, and what treatments are recommended?
4. What are the health risks associated with excessive vitamin A intake, and what symptoms should one watch for?
5. How does obesity impact the body's ability to absorb essential vitamins and minerals, and what dietary changes can help?


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1. What are the symptoms that differentiate vitamin A toxicity from carotenodermia and other disorders?
2. How does severe hypothyroidism affect the metabolism of carotene to vitamin A?
3. What is the prognosis for individuals diagnosed with vitamin A toxicity, and what steps are necessary for complete recovery?
4. What dietary changes can help prevent vitamin A toxicity and associated disorders?
5. In what ways can anorexia nervosa influence vitamin A metabolism and potentially lead to toxicity?


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1. What are the symptoms of chronic vitamin A toxicity in adults?
2. How long does it typically take for the symptoms of chronic toxicity to resolve?
3. What are the potential birth defects associated with high doses of vitamin A during pregnancy?
4. Can the effects of megadoses of vitamin A on fetal development be reversed?
5. What dietary changes can help prevent vitamin A toxicity while ensuring adequate intake?


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1. What are the key symptoms of vitamin B6 deficiency and how can they impact overall health?
2. What dietary sources are rich in vitamin B6 and how can they help prevent deficiencies?
3. How does a deficiency in vitamin B6 affect heme and nucleic acid biosynthesis in the body?
4. What are the potential health consequences of long-term vitamin B6 dependency?
5. How can vitamin B6 supplementation be effectively incorporated into a treatment plan for patients with metabolic disorders?


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1. What are the potential causes of secondary deficiency in vitamin B6?
2. What symptoms are associated with vitamin B6 deficiency, particularly in infants?
3. How is a vitamin B6 deficiency typically diagnosed without laboratory tests?
4. What treatment options are available for symptoms of peripheral neuropathy related to vitamin B6 deficiency?
5. Can seizures caused by impaired metabolism of vitamin B6 be effectively managed with anticonvulsants?


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1. What are the primary causes of vitamin B6 deficiency in adults?
2. How can excessive processing of foods lead to dietary vitamin B6 deficiency?
3. What symptoms are associated with a vitamin B6 deficiency?
4. In what ways can vitamin B6 deficiency contribute to vascular disorders?
5. What treatments are effective for addressing vitamin B6 deficiency?


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1. What are the potential causes of seizures in infants that may indicate a vitamin B6 deficiency?
2. How can normocytic, microcytic, or sideroblastic anemia be linked to vitamin deficiencies?
3. What are the clinical signs that would lead a physician to suspect vitamin B6 deficiency in a patient with refractory seizures?
4. What dietary changes can help prevent vitamin B6 deficiency in infants?
5. What treatment options are available for infants diagnosed with seizures due to vitamin B6 deficiency?


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1. What are the common symptoms of nutritional disorders associated with alcoholism?  
2. How does protein-energy undernutrition affect metabolic functions in the body?  
3. What dietary deficiencies are typically observed in individuals with nutritional disorders?  
4. What are the potential treatments for vitamin and mineral imbalances in patients suffering from nutritional disorders?  
5. How can obesity be linked to underlying nutritional disorders in patients?  


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1. What are the common causes of vitamin B6 deficiency and how can they be corrected?
2. How is vitamin B6 deficiency diagnosed and what laboratory tests are used to assess its status?
3. What is the recommended treatment for adults with vitamin B6 deficiency, and how does it vary for different causes of the deficiency?
4. What are the potential side effects and risks associated with taking high doses of pyridoxine?
5. In what situations may individuals require larger doses of pyridoxine beyond the daily recommended intake?


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1. What are the common symptoms associated with vitamin D deficiency in adults?
2. How can a deficiency in vitamin B12 affect the central nervous system?
3. What dietary changes can help manage obesity-related metabolic disorders?
4. What are the potential causes of iron deficiency anemia in individuals with a balanced diet?
5. How can supplementation of essential vitamins and minerals alleviate symptoms of certain nutritional disorders?


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1. What are the symptoms associated with a vitamin B6 deficiency?
2. How does vitamin B12 contribute to myelin synthesis and repair in the body?
3. What dietary changes can help prevent vitamin B deficiencies?
4. What are the potential long-term effects of stopping vitamin B6 supplementation?
5. How does the metabolism of nucleic acids relate to vitamin B12 activity?


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1. What role does intrinsic factor play in the absorption of vitamin B12 and how can a deficiency of intrinsic factor lead to nutritional disorders?
2. What are the potential symptoms of vitamin B12 deficiency in individuals who have impaired gastric acid secretion?
3. How does the cleaving of the B12-R protein complex in the small intestine affect the overall absorption of vitamin B12?
4. What dietary sources are rich in vitamin B12 and how can a lack of these foods contribute to nutritional disorders?
5. What treatments are available for individuals diagnosed with vitamin B12 deficiency-related anemia?


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1. What role does transcobalamin II play in the delivery of vitamin B12 to tissues, and how does this relate to vitamin B12 deficiency disorders?
2. How long can the liver store vitamin B12, and what implications does this have for individuals who stop consuming vitamin B12-rich foods?
3. What are the potential health consequences of a lack of enterohepatic reabsorption of vitamin B12?
4. Are there any symptoms associated with long-term vitamin B12 deficiency, and how can they be treated?
5. What are the risks of taking large amounts of vitamin B12 as a supplement, despite its low toxicity?


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1. What are the primary causes of vitamin B12 deficiency in individuals following a vegan diet?  
2. What symptoms are associated with megaloblastic anemia due to vitamin B12 deficiency?  
3. How does vitamin B12 deficiency affect the white matter of the spinal cord and brain?  
4. What diagnostic methods are used to determine vitamin B12 deficiency?  
5. What treatment options are available for individuals diagnosed with vitamin B12 deficiency?  


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1. What is the purpose of the Schilling test in diagnosing nutritional disorders?
2. How does vitamin B12 deficiency differ from folate deficiency in terms of treatment?
3. What are the potential risks of using folate instead of vitamin B12 in the treatment of anemia?
4. What are the symptoms associated with vitamin B12 deficiency?
5. What are the possible causes of vitamin B12 malabsorption?


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1. What are the potential causes of vitamin B12 deficiency in individuals following a vegan diet?
2. How can breastfed infants of vegan mothers develop vitamin B12 deficiency?
3. What symptoms are associated with inadequate vitamin B12 intake in children?
4. What dietary sources are recommended to prevent vitamin B12 deficiency in vegans?
5. How does the rapid growth rate of infants impact their vitamin B12 requirements?


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1. What are the common causes of vitamin B12 deficiency in the elderly?
2. How does inadequate absorption of vitamin B12 relate to gastric surgery and chronic pancreatitis?
3. What role does intrinsic factor play in the absorption of vitamin B12, and how does its loss lead to pernicious anemia?
4. Can certain medications contribute to vitamin B12 deficiency, and if so, which ones?
5. What are the potential consequences of untreated vitamin B12 deficiency in individuals with inflammatory bowel disease?


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1. What are the potential long-term health risks associated with untreated classic pernicious anemia?
2. How does vitamin B12 deficiency lead to subacute combined degeneration of the nervous system?
3. What symptoms might indicate the presence of demyelinating or axonal peripheral neuropathies in patients with vitamin B12 deficiency?
4. What dietary changes or treatments are recommended for individuals diagnosed with classic pernicious anemia?
5. How does the deficiency of vitamin B12 specifically affect brain and spinal cord white matter?


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1. What are the common symptoms and signs associated with anemia?
2. What dietary deficiencies can lead to the development of anemia?
3. What are the potential causes of anemia in individuals?
4. How can anemia be treated or managed through dietary changes?
5. What role do vitamins and minerals play in preventing anemia?


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1. What are the common symptoms associated with chronic nutritional disorders and how can they vary in severity?
2. How can splenomegaly and hepatomegaly be related to underlying nutritional deficiencies?
3. What gastrointestinal symptoms are indicative of potential nutritional imbalances, and how do they manifest in patients?
4. How does glossitis present in patients with nutritional disorders, and what are its common causes?
5. What neurologic symptoms might arise from nutritional deficiencies, and how can they occur without accompanying hematologic abnormalities?


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1. What are the early symptoms of a nutritional disorder that affects position and vibratory sensation in the extremities?  
2. How does spasticity develop in the later stages of certain nutritional disorders?  
3. What nutritional deficiencies could lead to decreased vibratory sensation and hyporeflexia in patients?  
4. What sensory modalities are typically spared in nutritional disorders affecting the extremities?  
5. How can dietary changes help manage the symptoms of a nutritional disorder characterized by ataxia and weakness?  


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1. What are the psychological symptoms associated with severe vitamin B12 deficiency?
2. How can megaloblastic madness be differentiated from other forms of dementia?
3. What diagnostic tests are recommended for confirming a vitamin B12 deficiency?
4. What advanced neurological symptoms may indicate a worsening nutritional disorder related to vitamin B12?
5. How does postural hypotension present in patients with severe vitamin deficiencies?


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1. What laboratory tests are essential for diagnosing megaloblastic anemia related to vitamin B12 and folate deficiencies?  
2. How can severe neurologic disease manifest in patients without accompanying anemia or macrocytosis?  
3. What are the common symptoms associated with megaloblastic anemia?  
4. What dietary changes can help prevent vitamin B12 and folate deficiencies?  
5. What treatment options are available for individuals diagnosed with megaloblastic anemia?  


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1. What are the key indicators of vitamin B12 deficiency in patients presenting with megaloblastic anemia?  
2. How can serum methylmalonic acid (MMA) levels assist in diagnosing vitamin B12 deficiency?  
3. Why is it important to differentiate between vitamin B12 deficiency and folate deficiency in patients with anemia?  
4. What role does holotranscobalamin II play in assessing vitamin B12 status, and what level indicates deficiency?  
5. In what situations is the Schilling test considered necessary for diagnosing vitamin B12 deficiency?  


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1. What does the Schilling test measure in relation to vitamin B12 absorption?
2. How does the presence of intrinsic factor affect the results of the Schilling test?
3. What could reduced urinary excretion of radiolabeled vitamin B12 indicate regarding a patient's nutrient absorption?
4. In what scenarios might the Schilling test yield difficult or inconclusive results?
5. What are the recommended treatments for patients diagnosed with vitamin B12 deficiency?


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1. What are the symptoms of vitamin B12 deficiency and how can they be identified?
2. What dietary sources are rich in vitamin B12 to help prevent deficiency?
3. How does a nasal gel preparation of vitamin B12 compare to other forms of supplementation in terms of efficacy?
4. What are the potential causes of vitamin B12 deficiency in adults?
5. What treatments are available for individuals diagnosed with vitamin B12 deficiency?


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1. What are the implications of intrinsic factor absence on vitamin B12 absorption and related nutritional disorders?  
2. How can large oral doses of vitamins help mitigate deficiencies in individuals lacking intrinsic factor?  
3. What symptoms might indicate a deficiency in nutrients that require intrinsic factor for absorption?  
4. What dietary strategies can be employed to address nutritional disorders related to vitamin absorption?  
5. How does the body's mass action mechanism influence the treatment of vitamin deficiencies in patients with metabolic disorders?  


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1. What are the potential consequences of untreated vitamin B12 deficiency?
2. How is the effectiveness of vitamin B12 treatment monitored in patients?
3. What is the recommended dosage and frequency of vitamin B12 injections for severe deficiency?
4. How long does it typically take for hematologic abnormalities to correct with vitamin B12 treatment?
5. Why might neurological symptoms persist even after hematologic improvements are observed in vitamin B12 deficiency?


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1. What are the common neurologic symptoms associated with vitamin B12 deficiency?
2. How can a deficiency in folate lead to neurologic complications?
3. What dietary changes can help alleviate persistent neurologic symptoms related to nutritional disorders?
4. Which metabolic disorders are linked to neurologic symptoms and how can they be treated?
5. What role do essential fatty acids play in preventing neurologic symptoms related to dietary deficiencies?


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1. What are the common symptoms of vitamin deficiency disorders, and how can they be identified?
2. What are the primary causes of vitamin dependency and how do they affect overall health?
3. How can vitamin toxicity occur, and what are its potential health implications?
4. What dietary changes can be implemented to prevent or treat specific vitamin and mineral deficiencies?
5. How do metabolic disorders influence vitamin and mineral absorption in the body?


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1. What are the long-term cognitive effects of untreated vitamin B12 deficiency in elderly individuals?
2. How can vegan mothers ensure their infants receive adequate vitamin B12?
3. What are the primary symptoms associated with severe vitamin C deficiency or scurvy?
4. In what ways does vitamin C contribute to wound healing and recovery from burns?
5. What dietary sources can help prevent vitamin C deficiency in populations at risk?


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1. What are the potential nutritional deficiencies that could lead to impaired bone growth in infants and children?
2. What symptoms might indicate a nutritional disorder affecting bone health in young children?
3. What dietary changes can help prevent impaired bone growth in infants and children?
4. How do metabolic disorders contribute to the risk of nutritional deficiencies that affect bone development?
5. What role do vitamins and minerals play in maintaining healthy bone growth in children?


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1. What are the clinical symptoms associated with severe vitamin C deficiency and scurvy?
2. What dietary factors can increase the risk of developing vitamin C deficiency in adults?
3. How does cooking or sterilization of food affect the vitamin C content in diets?
4. What is the recommended treatment for individuals diagnosed with severe vitamin C deficiency?
5. What physiological changes occur in the body due to a lack of vitamin C, particularly related to connective tissues and bone health?


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1. What are the symptoms associated with vitamin C deficiency in both children and adults?
2. How does vitamin C deficiency lead to impaired bone tissue formation in children?
3. What are the potential complications of prolonged vitamin C depletion in adults?
4. What dietary sources are rich in vitamin C that can help prevent deficiency?
5. What treatment options are available for individuals suffering from symptoms of vitamin C deficiency?


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1. What are the common symptoms associated with a vitamin deficiency that affects connective tissues?
2. How does follicular hyperkeratosis relate to nutritional disorders?
3. What dietary deficiencies can lead to swollen, purple gums and bleeding?
4. What are the potential long-term effects of untreated nutritional disorders on dental health?
5. What treatments are available for severe deficiencies that cause symptoms like loose teeth and coiled hair?


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1. What are the common symptoms associated with nutritional disorders that lead to poor wound healing and spontaneous hemorrhages?
2. How can deficiencies in certain vitamins or minerals contribute to femoral neuropathy and lower-extremity edema?
3. What dietary changes can help prevent the development of secondary infections in individuals with nutritional disorders?
4. What are the potential causes of painful bleeding or effusions within joints in the context of nutritional deficiencies?
5. How can the management of nutritional disorders reduce the risk of symptoms like ecchymoses and hemorrhage in the skin?


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1. What are the common symptoms associated with vitamin D deficiency and how can they impact overall health?
2. How can excessive intake of vitamin A lead to toxicity, and what are the signs to look out for?
3. What dietary changes can help prevent iron deficiency anemia in individuals with restrictive diets?
4. What metabolic disorders are linked to vitamin B12 deficiency, and what treatments are available?
5. How does obesity influence the absorption of essential vitamins and minerals in the body?


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1. What are the common skin or gingival signs associated with vitamin C deficiency?
2. What risk factors contribute to the development of vitamin C deficiency?
3. How is vitamin C deficiency diagnosed clinically in patients?
4. What laboratory tests can confirm a diagnosis of vitamin C deficiency?
5. What dietary changes can help prevent vitamin C deficiency and its associated symptoms?


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1. What are the common symptoms associated with anemia, and how can they be recognized?
2. What dietary deficiencies are most commonly linked to the development of anemia?
3. What are the primary causes of anemia related to nutritional disorders?
4. How can anemia be treated or managed through dietary changes?
5. What role do vitamins and minerals play in preventing anemia and other nutritional disorders?


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1. What skeletal changes are indicative of childhood scurvy as observed in x-rays?
2. How does a deficiency in vitamin C relate to bleeding and coagulation abnormalities?
3. What are the common symptoms of scurvy in children, and how can they be identified?
4. What dietary sources can help prevent scurvy in children?
5. Are there any specific treatments or interventions for managing childhood scurvy?


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1. What are the early symptoms of nutritional disorders that can lead to changes resembling atrophy in bone structure?
2. How does the loss of trabeculae contribute to the development of a ground-glass appearance in bone imaging?
3. What specific dietary deficiencies may result in the thinning of the cortex and the appearance of calcified cartilage in bones?
4. What treatment options are available for individuals exhibiting rarefaction or linear fractures associated with nutritional disorders?
5. How can nutritional imbalances contribute to the compression of the epiphysis in growing children?


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1. What are the laboratory criteria for diagnosing vitamin C deficiency in adults?
2. How can scurvy be differentiated from other conditions such as arthritis and hemorrhagic disorders?
3. What are the common symptoms associated with scurvy and how do they present clinically?
4. What is the recommended treatment regimen for adults diagnosed with scurvy?
5. How does a deficiency in vitamin C affect the healing of subperiosteal hemorrhages?


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1. What are the symptoms of chronic gingivitis associated with vitamin C deficiency?
2. How does a deficiency in vitamin C lead to subcutaneous hemorrhage?
3. What dietary recommendations should be made to prevent vitamin C deficiency in smokers?
4. What is the daily recommended intake of vitamin C for men and women?
5. How can chronic gingivitis be effectively treated or managed through dietary changes?


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1. What are the potential health risks associated with excessive vitamin C intake above the upper limit of 2000 mg/day?
2. How does vitamin D deficiency manifest in adults, particularly as they age?
3. What dietary sources are most effective for increasing vitamin D levels in individuals who have limited sun exposure?
4. In what ways can high doses of vitamin C interfere with the body's antioxidant-prooxidant balance?
5. What are the implications of low vitamin D levels in breastfed infants compared to those consuming fortified cow's milk?


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1. How does sunscreen use affect vitamin D synthesis in individuals with dark skin pigmentation?
2. What are the potential health implications of vitamin D deficiency in dark-skinned individuals who frequently use sunscreen?
3. What dietary sources can help compensate for reduced vitamin D synthesis due to sunscreen use?
4. Are there specific symptoms associated with vitamin D deficiency that may be more pronounced in those with darker skin?
5. What treatment options are available for individuals with a vitamin D deficiency related to sun exposure and skin pigmentation?


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1. What are the common symptoms associated with vitamin deficiencies and how can they be identified?
2. What are the potential health risks of vitamin toxicity and how can they be mitigated?
3. What dietary changes can help prevent nutritional disorders related to vitamin deficiencies?
4. How can one determine if they are experiencing a vitamin dependency or a deficiency?
5. What are the recommended treatments for individuals suffering from metabolic disorders due to vitamin imbalances?


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1. What are the primary causes of vitamin D deficiency and how does inadequate sunlight exposure contribute to it?  
2. What are the symptoms associated with vitamin D deficiency, and how can they impact overall health?  
3. How does vitamin D influence calcium and phosphate absorption in the body, and what are the implications for bone health?  
4. In what ways can vitamin D and its metabolites be used to treat specific health conditions such as psoriasis and certain cancers?  
5. How is the conversion of vitamin D to its active form regulated, and what role do parathyroid hormone and serum concentrations of calcium and phosphate play in this process?  


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1. What are the symptoms of rickets in children and osteomalacia in adults caused by vitamin D deficiency?  
2. How does a deficiency in vitamin D contribute to the development of osteoporosis?  
3. What dietary changes can help prevent the conditions associated with vitamin D deficiency?  
4. What role do calcium and phosphate play in the treatment of vitamin D deficiency-related disorders?  
5. How is vitamin D deficiency diagnosed and what are the recommended treatments?  


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1. What are the common symptoms associated with vitamin D deficiency?
2. How can dietary changes help prevent obesity-related metabolic disorders?
3. What are the primary causes of iron-deficiency anemia, and how can it be treated?
4. Which vitamins and minerals are most commonly associated with nutritional imbalances in adults?
5. What strategies can be implemented to prevent nutritional disorders in children?


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string_value:
1. What are the common causes of vitamin D deficiency and how do they lead to conditions like rickets and osteomalacia?
2. How does hypoparathyroidism affect vitamin D absorption and contribute to mineralization disorders?
3. What are the consequences of vitamin D deficiency on calcium and phosphate levels in the body?
4. How do renal tubular disorders contribute to impaired metabolism of vitamin D and associated health issues?
5. What dietary factors can lead to inadequate calcium intake and how does this interact with vitamin D deficiency?


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1. What are the primary causes of vitamin D deficiency in the elderly population?
2. How does inadequate sunlight exposure contribute to nutritional disorders related to vitamin D?
3. What are the recommended guidelines for sunlight exposure to prevent vitamin D deficiency?
4. Which communities are most at risk for inadequate vitamin D intake and what factors contribute to this risk?
5. How can malabsorption issues lead to a deficiency in dietary vitamin D?


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1. What are the potential causes of vitamin D deficiency related to renal disorders?
2. How does the absence of 1,25(OH)2D production affect bone health in individuals with chronic renal disorders?
3. What are the symptoms of type I hereditary vitamin D-dependent rickets, and how is it diagnosed?
4. In what ways can hepatic dysfunction impact vitamin D metabolism and overall health?
5. What treatment options are available for managing familial hypophosphatemia and its related complications?


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1. What are the common symptoms associated with a vitamin D deficiency?
2. How can a vitamin B12 deficiency impact neurological health?
3. What dietary changes can help prevent iron deficiency anemia?
4. What are the potential consequences of excessive vitamin A intake?
5. How can obesity influence the metabolism of vitamins and minerals in the body?


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1. What are the potential symptoms of vitamin D deficiency caused by the use of certain anticonvulsants and glucocorticoids?
2. How do mutations in the 1,25(OH)2D receptor contribute to Type II hereditary vitamin D-dependent rickets?
3. What dietary changes can help mitigate the increased need for vitamin D supplementation in individuals taking glucocorticoids?
4. What are the different forms of Type II hereditary vitamin D-dependent rickets and how do they manifest clinically?
5. How can resistance to the effects of vitamin D affect overall health and metabolism?


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1. What role does the receptor play in the metabolism of nutrients in the gut and kidney?
2. How can imbalances in this receptor affect bone health and lead to nutritional disorders?
3. What are the potential symptoms associated with deficiencies related to this receptor's function?
4. What dietary changes can help regulate the metabolism influenced by this receptor in individuals with obesity?
5. What treatments are available for metabolic disorders linked to the dysfunction of this receptor?


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1. What are the common symptoms of Vitamin D deficiency in infants and children?
2. How does Vitamin D deficiency during pregnancy affect fetal development?
3. What are the physiological effects of ineffective 1,25(OH)2D due to non-functional receptors?
4. What are the characteristic signs of rickets in young infants?
5. How does Vitamin D deficiency contribute to bone pain and muscle weakness at any age?


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1. What are the common symptoms of vitamin D deficiency in older children and adolescents?
2. How does hypocalcemia lead to tetany, and what are its symptoms?
3. What deformities can develop in children due to nutritional deficiencies, specifically related to vitamin D?
4. How can maternal nutritional deficiencies affect the health of neonates?
5. What are the potential complications of osteomalacia in adults?


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1. What are the common symptoms and signs that may indicate a deficiency in vitamin D in the elderly population?
2. How can inadequate sunlight exposure contribute to the development of rickets in infants?
3. What diagnostic tests are essential for differentiating vitamin D deficiency from other causes of bone demineralization?
4. In what ways can the clinical presentation of tetany due to infantile rickets be confused with seizures from other causes?
5. How can dietary intake of vitamin D be improved to prevent conditions like osteomalacia in the elderly?


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1. What are the early radiographic signs of rickets in children?
2. How do bone changes in rickets affect the structure and function of the radius and ulna?
3. What are the characteristic deformities associated with weakened bone shafts in rickets?
4. What dietary deficiencies contribute to the development of rickets?
5. What treatment options are available for correcting the bone changes caused by rickets?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency, and how can they be identified?
2. What dietary sources can help prevent vitamin B12 deficiency, and who is at higher risk for this condition?
3. How does excessive intake of vitamin A lead to toxicity, and what are the signs to watch for?
4. What metabolic disorders are commonly linked to deficiencies in essential minerals, and what treatments are available?
5. How can obesity contribute to nutritional imbalances, and what dietary changes can help address these issues?


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string_value:
1. What are the symptoms associated with vitamin D deficiency in adults?  
2. How can the presence of pseudofractures and Looser's lines indicate a nutritional disorder?  
3. What role does serum 25(OH)D play in diagnosing vitamin D deficiency?  
4. What are the potential consequences of bone demineralization in the spine, pelvis, and lower extremities?  
5. What dietary changes can help prevent vitamin D deficiency and its associated health issues?  


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1. What are the serum levels of 25(OH)D considered optimal for health, and what are the potential benefits of higher levels?  
2. How can serum levels of 1,25(OH)2D and urinary calcium concentration help in diagnosing vitamin D deficiency?  
3. What are the differences in serum calcium and phosphate levels in various forms of vitamin D deficiency?  
4. What is the recommended treatment protocol for correcting calcium and phosphate deficiencies in patients with osteomalacia or rickets?  
5. How quickly can serum levels of 25(OH)D and 1,25(OH)2D increase after administering vitamin D supplementation?  


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1. What changes in serum calcium and phosphate levels indicate the effectiveness of treatment for a nutritional disorder?
2. How long does it typically take for calcium and phosphate to become visible in bones on x-rays after treatment initiation?
3. What is the recommended maintenance dose of vitamin D after initial treatment for a calcium-related nutritional disorder?
4. What are the indications for administering intravenous calcium salts in the context of vitamin D supplementation?
5. How does the serum alkaline phosphatase level change in response to treatment for nutritional disorders affecting mineral metabolism?


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1. What is the recommended daily allowance of vitamin D for individuals over 70 years old, and how does it compare to the needs of elderly patients to maintain adequate vitamin D levels?
2. What are the potential health risks associated with vitamin D resistance in elderly patients suffering from rickets and osteomalacia?
3. How does the dosage of vitamin D required to treat elderly patients with vitamin D-resistant rickets differ from that of individuals with inadequate intake?
4. What symptoms might indicate a vitamin D deficiency in elderly patients, and how can these be differentiated from those of other nutritional disorders?
5. What considerations should be made when prescribing vitamin D supplementation to elderly patients, especially regarding the upper limit of daily intake?


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1. How does a defect in 25(OH)D production affect vitamin D levels and what treatment options are available?
2. What are the recommended dosages of 1,25(OH)2D for patients with type I and type II hereditary vitamin D-dependent rickets?
3. What dietary strategies can be implemented to prevent vitamin D deficiency in at-risk communities?
4. What is the role of sunlight exposure in maintaining vitamin D status, and what risks are associated with it?
5. How does kidney dysfunction impact the need for vitamin D supplementation in patients?


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string_value:
1. What are the common symptoms associated with vitamin D deficiency, and how can they be treated?
2. What dietary changes can help manage obesity and its related health conditions?
3. What are the potential causes of iron deficiency anemia, and how can it be diagnosed?
4. How do metabolic disorders affect nutrient absorption and overall health?
5. What are the implications of calcium imbalance on bone health, and what treatments are available?


