bound niacin into a more absorbable form. pellagra is not problematic in countries which traditionally prepare their corn in this way, but is a problem in other countries where unprocessed corn is main source of caloric intake. though pellagra predominantly occurs in developing countries, sporadic cases of pellagra may be observed within industrialized nations, primarily in chronic alcoholics and patients living with functional absorption complications. symptoms pellagra is classically characterized by four 4 "d's": diarrhea, dermatitis, dementia, and death. neuropsychiatric manifestations of pellagra include headache, irritability, poor concentration, anxiety, hallucinations, stupor, apathy, psychomotor unrest, photophobia, tremor, ataxia, spastic paresis, fatigue, and depression. symptoms of fatigue and insomnia may progress to encephalopathy characterized by confusion, memory loss, and psychosis. those affected by pellagra may undergo pathological alterations in the nervous system. findings may include demylenation and degeneration of various affected parts of the brain, spinal cord, and peripheral nerves. treatment prognosis of deficiency is excellent with treatment. without, pellagra will gradually progress and lead to death within 4–5 years, often a result of malnutrition from prolonged diarrhea, or complications as caused by concurrent infections or neurological symptoms. symptoms of pellagra can be cured with exogenous administration of nicotinic acid or nicotinamide. flushing occurs in many patients treated therapeutically with nicotinic acid, and as a result, nicotinamide holds more clinical value as it is not associated with the same uncomfortable flushing. the adult dose of nicotinamide is 100 mg taken orally every 6 hours until resolution of major acute symptoms, followed with oral administration of 50 mg every 8–12 hours until skin lesions heal. for children, treatment involves oral ingestion of 10–15 mg of nicotinamide, depending on weight, every 6 hours until signs and symptoms are resolved. severe cases require 1 gram every 3–4 hours, administered parenterally. oral nicotinamide has been promoted as an over-the-counter drug for the treatment of alzheimer's dementia. conversely, no clinically significant effect has been found for the drug, as nicotinamide administration has not been found to promote memory functions in patients with mild to moderate dementia of either alzheimer's, vascular, or fronto-temporal types. this evidence suggests that nicotinamide may treat dementia as related to pellagra, but administration does not effectively treat other types of dementia. prevention the best method of prevention is to eat foods rich in b3. generally, this involves the intake of a protein-rich diet. foods that contain high concentrations of niacin in the free form include beans and organ meat, as well as enriched grain and cereal products. while niacin is present in corn and other grains, the bioavailability of the nutrient is much less than it is in protein-rich sources. different methods of processing corn may result in a higher degree of bioavailability of the vitamin. though treatment with niacin does little to alter the effects of alzheimer's dementia, niacin intake from foods is inversely associated with the disease. folate (vitamin b9) folate deficiency can disrupt neurulation and neurogenesis. maternal folic acid intake around the time of conception prevents neural tube defects. furthermore, folic acid intake was recently associated with incidence of autism. enriched white flour is fortified with folic acid in the united states and many other countries. however the european union does not have mandatory folic acid fortification. although the protective effects of folic acid are well documented, there remains legitimate concern that fortification could lead to toxic levels in a subset of the population. for example, elevated levels of folic acid can interact with vitamin b12 deficiency to cause neurodegeneration. furthermore, folic acid and iron can interact to exacerbate malaria. folic acid is the most oxidized and stable form of folate, and can also be referred to as vitamin b9. it rarely occurs naturally in foods, but it is the form used in vitamin supplements as well as fortified food products. folate coenzymes are involved in numerous conversion processes within the body, including dna synthesis and amino acid interconversions. folate and vitamin b12 play a vital role in the synthesis of s-adenosylmethionine, which is of key importance in the maintenance and repairment of all cells, including neurons. in addition, folate has been linked to the maintenance of adequate brain levels of cofactors necessary for chemicals reactions that lead to the synthesis of serotonin and catecholamine neurotransmitters. folate has a major, but indirect role in activities which help to direct gene expression and cell proliferation. these activities occur at a greatly increased rate during pregnancy, and depend on adequate levels of folate within blood plasma. concentrations of blood plasma folate and homocysteine concentrations are inversely related, such that an increase in dietary folate decreases homocysteine concentration. thus, dietary intake of folate is a major determinant of homocysteine levels within the body. autoantibodies against folate receptor alpha have been found in up to 75% of children with autism. deficiencies folate deficiency most commonly arises from insufficient folate intake from the diet, but may also stem from inefficient absorption or metabolic utilization of folate, usually a result of genetic variation. the relationship between folate and b12 is so interdependent that deficiency in either vitamin can result in megaloblastic anemia, characterized by organic mental change. the process of neural tube transformation into structures that will eventually develop into the central nervous system is known as neurulation, the success of which is dependent on the presence of folate within the body. this process begins in the human approximately 21 days after conception, and is completed by 28 days. thus, a woman may not even be aware of her pregnancy by the time the process of neurulation is complete, potentially causing severe consequences in the development of the fetus. functional problems in the absorption and utilization of vitamins may also play a role in folate deficiencies within the elderly. symptoms anencephaly is the most common presentation of neural tube defects the link between levels of folate and altered mental function is not large, but is sufficient enough to suggest a causal association. deficiency in folate can cause an elevation of homocysteine within the blood, as the clearance of homocysteine requires enzymatic action dependent on folate, and to a lesser extent, vitamins b6 and b12. elevated homocysteine has been associated with increased risk of vascular events, as well as dementia. differences lie in the presentation of megaloblastic anemia induced by either folate or b12 deficiency. megaloblastic anemia related to deficiency in b12 generally results in peripheral neuropathy, whereas folate-related anemia often results in affective, or mood disorders. neurological effects are not often associated with folate-related megaloblastic anemia, although demyelinating disorders may eventually present. in one study, mood disturbances were recorded for the majority of patients presenting with megaloblastic anemia in the absence of b12 deficiency. in addition, folate concentrations within blood plasma have been found to be lower in patients with both unipolar and bipolar depressive disorders when compared with control groups. in addition, depressive groups with low folate concentrations responded less well to standard antidepressant therapy than did those with normal levels within plasma. however, replication of these findings are less robust. the role of folic acid during pregnancy is vital to normal development of the nervous system in the fetus. a deficiency in folate levels of a pregnant woman could potentially result in neural tube disorder, a debilitating condition in which the tubes of the central nervous system do not fuse entirely. ntds are not to be confused with spina bifida, which does not involve neural elements. neural tube defects can present in a number of ways as a result of the improper closure at various points of the neural tube. the clinical spectrum of the disorder includes encephalocele, craniorachischisis, and anencephaly. in addition, these defects can also be classified as open, if neural tissue is exposed or covered only by membrane, or can be classified as closed, if the tissue is covered by normal skin. intake of the vitamin has been linked to deficits in learning and memory, particularly within the elderly population. elderly people deficient in folate may present with deficits in free recall and recognition, which suggests that levels of folate may be related to efficacy of episodic memory. prevention because neurulation may be completed before pregnancy is recognized, it is recommended that women capable of becoming pregnant take about 400μg of folic acid from fortified foods, supplements, or a combination of the two in order to reduce the risk of neural tube defects. these major anomalies in the nervous system can be reduced by 85% with systematic folate supplementation occurring before the onset of pregnancy. the incidence of alzheimer's and other cognitive diseases has been loosely connected to deficiencies in folate. it is recommended for the elderly to consume folate through food, fortified or not, and supplements in order to reduce risk of developing the disease. good sources of folate include liver, ready-to-eat breakfast cereals, beans, asparagus, spinach, broccoli, and orange juice. choline choline is an important methyl donor involved in one-carbon metabolism that also becomes incorporated into phospholipids and the neurotransmitter acetylcholine. because of its role in cellular synthesis, choline is an important nutrient during the prenatal and early postnatal development of offspring as it contributes heavily to the development of the brain. a study found that rats that were given supplements of choline in utero or in the weeks following birth had superior memories. the changes appeared to be a result of physical changes to the hippocampus, the area of the brain responsible for memory. furthermore, choline can reduce some of the deleterious effects of folate deficiency on neurogenesis. while choline during development is important, adult levels of choline are also important. choline has been shown to increase the synthesis and release of acetylcholine from neurons, which in turn increases memory. a double-blind study was conducted using normal college students (no neurological disorders). results showed that twenty-five grams of phosphatidylcholine (another form of choline) created a significant improvement in explicit memory, measured by a serial learning task, however this improvement may be attributed to the improvement of slow learners. another study found that a single ten-gram oral dose of choline, given to normal volunteers (again, without neurological disorders) significantly decreased the number of trials needed to master a serial-learning word test. this increase in memory is particularly beneficial to memory loss experienced by old age. a study conducted on rats who, like humans, had an age-related loss of memory were tested on how choline affected memory. the results showed that rats who had a chronic low-choline diet showed greater memory loss then their same-age control counterparts, while rats who had choline-enriched diets showed a diminished memory loss compared to both the choline-low diet and control rat groups. furthermore, young rats who were choline-deficient performed as poorly on memory tasks as older rats while older rats that were given choline supplements performed as well as three-month-old rats. deficiencies and treatments despite the wide range of foods that choline is found in, studies have shown that the mean choline intake of men, women and children are below the adequate intake levels. it is important to note that not enough choline is naturally produced by the body, so diet is an important factor. people who consume a large quantity of alcohol may be at an increased risk for choline deficiency. sex and age also plays a role, with premenopausal females being less sensitive to choline deficiency than either males or postmenopausal females. this has been theorized to be a result of premenopausal women having an increased ability to synthesize choline in some form, which has been confirmed in studies on rats. in such instances of deficiency, choline supplements or (if able) dietary changes may be beneficial. good sources of choline include liver, milk, eggs and peanuts. there is further evidence to suggest that choline supplements can be used to treat people who have neurological disorders as well we memory defects. oral doses of cdp-choline (another form of choline) given to elderly subjects with memory deficits, but without dementia, for four weeks showed improved memory in free recall tasks, but not in recognition tests. in a second study, patients with early alzheimer-type dementia were treated with twenty-give gram doses of phosphatidylcholine every day for six months. slightly improvements were shown in memory tests compared to the placebo control group. other studies conducted did not find any such improvement. cobalamin (vitamin b12)