Effect of Homocysteine-Lowering Treatment With Folic Acid and B Vitamins on Risk of Type 2 Diabetes in Women Maternal dietary folate, folic acid and vitamin D intakes during pregnancy and lactation and the risk of cows' milk allergy in the offspring. Improving neuropathy scores in type 2 diabetic patients using micronutrients supplementation. Potential Antioxidant Effects of Zinc and Chromium Supplementation in People with Type 2 Diabetes Mellitus Complementary therapy in diabetic patients with chronic complications: a pilot study. [Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation]. Vitamin and Mineral Supplements: What Clinicians Need to Know. Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale Comparison of the effects of vitamins and/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes. Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile: a randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance. Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study. Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation. The Age-Related Eye Disease Study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Maternal vitamin D supplementation during pregnancy Maternal multiple micronutrient supplementation has limited impact on micronutrient status of Bangladeshi infants compared with standard iron and folic acid supplementation. Effect of docosahexaenoic acid supplementation on the macular function of patients with Best vitelliform macular dystrophy: randomized clinical trial. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress, inflammation, and malnutrition in hemodialysis patients. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence [Comparison of the effects of alpha-keto/ amino acid supplemented low protein diet and diabetes diet in patients with diabetic nephropathy]. Study protocol: a randomised placebo-controlled clinical trial to study the effect of vitamin D supplementation on glycaemic control in type 2 Diabetes Mellitus SUNNY trial Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. Vitamin D and calcium intake in relation to type 2 diabetes in women. Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes. Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-month follow-up Effects of Lutein and Docosahexaenoic Acid Supplementation on Macular Pigment Optical Density in a Randomized Controlled Trial Nutritional Supplementation with N‐3 Fatty Acids and Antioxidants in Patients with Crohn's Disease in Remission: Effects on Antioxidant Status and Fatty Acid Profile Prospective open-label study on the efficacy and tolerability of a combination of nutritional supplements in primary infertile patients with idiopathic astenoteratozoospermia. The Protective Effects of α-Lipoic Acid on Kidneys in Type 2 Diabetic Goto-Kakisaki Rats via Reducing Oxidative Stress Effect of Vitamin D Supplementation on Glucose Control and Inflammatory Response in Type II Diabetes: A Double Blind, Randomized Clinical Trial [Changes in plasma zinc and folic acid concentrations in pregnant adolescents submitted to different supplementation regimens].
OBJECTIVE Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress , systemic inflammation , and endothelial dysfunction . We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes . RESEARCH DESIGN AND METHODS The Women 's Antioxidant and Folic Acid Cardiovascular Study ( WAFACS ) , a r and omized , double-blind , placebo-controlled trial of 5,442 female health professionals aged ≥40 years with a history of cardiovascular disease ( CVD ) or three or more CVD risk factors , included 4,252 women free of diabetes at baseline . Participants were r and omly assigned to either an active treatment group ( daily intake of a combination pill of 2.5 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 ) or to the placebo group . RESULTS During a median follow-up of 7.3 years , 504 women had an incident diagnosis of type 2 diabetes . Overall , there was no significant difference between the active treatment group and the placebo group in diabetes risk ( relative risk 0.94 [ 95 % CI 0.79–1.11 ] ; P = 0.46 ) , despite significant lowering of homocysteine levels . Also , there was no evidence for effect modifications by baseline intakes of dietary folate , vitamin B6 , and vitamin B12 . In a sensitivity analysis , the null result remained for women compliant with their study pills ( 0.92 [ 0.76–1.10 ] ; P = 0.36 ) . CONCLUSIONS Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD Maternal nutrient intake during pregnancy and lactation potentially influences the development of allergic diseases . Cows ' milk allergy ( CMA ) is often the first manifestation of atopic diseases , but the impact of early nutritional influences on CMA has not been explored . The associations between maternal intakes of folate , folic acid and vitamin D during pregnancy and lactation were addressed in a prospect i ve , population -based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study . Mothers of 4921 children during pregnancy and 2940 children during lactation provided information on maternal dietary intake during the 8th month of pregnancy and the 3rd month of lactation using a detailed , vali date d FFQ . Information on diagnosed CMA in the offspring was obtained from a medical registry as well as queried from the parents . The Finnish food composition data base was used to calculate nutrient intake . Logistic regression was applied for statistical analyses .  Folate intake and folic acid and vitamin D supplement  use were associated with an increased risk of CMA in the offspring , whereas vitamin D intake from foods during pregnancy was associated with a decreased risk of CMA . Thus , maternal nutrient intake during pregnancy and lactation may affect the development of CMA in offspring . Supplementation with folic acid may not be beneficial in terms of CMA development , especially in children of allergic mothers . The association between dietary supplement use and CMA risk can at least partly be explained by increased health-seeking behaviour among more educated mothers who also use more dietary supplements AIM The aim of the present study was to determine if micronutrients supplementation can improve neuropathy indices in type 2 diabetes . MATERIAL S AND METHODS In this r and omized , double-blind , placebo-controlled clinical trial , 75 type 2 diabetes patients were assigned to three treatment groups , receiving one of the following daily supplement for 4 months : Group MV : zinc ( 20 mg ) , magnesium ( 250 mg ) , vitamin C ( 200 mg ) and E ( 100 mg ) ; Group MVB : both of the above mineral and vitamin supplements plus vitamin B1 ( 10 mg ) , B2 ( 10 mg ) , B6 ( 10 mg ) , biotin ( 200 μg ) , B12 ( 10 μg ) and folic acid ( 1 mg ) ; Group P : placebo . RESULTS 67 patients completed the study . Neuropathic symptoms based on the MNSI question naire improved from 3.45 to 0.64 ( p=0.001 ) in group MVB , from 3.96 to 1.0 ( p=0.001 ) in group MV and from 2.54 to 1.95 in placebo group after 4 months . There was no significant difference between three treatment groups in MNSI examinations after 4 months supplementations . Over 4 months of treatment , patients showed no significant changes in glycemic control , capillary blood flow or electrophysiological measures in MV and MVB groups compared with placebo group . CONCLUSIONS These studies suggest that micronutrients supplementation might ameliorate diabetic neuropathy symptoms Objective : To determine the effects of combined zinc ( Zn ) and chromium ( Cr ) supplementation on oxidative stress and glucose homeostasis of people with type 2 diabetes . Design : Tunisian adult subjects with HbA1C > 7.5 % were supplemented for 6 months with 30 mg/d of Zn as Zn gluconate or 400 μg/d of Cr as Cr pidolate or combined Zn/Cr supplementation or placebo . The effects of supplementation on plasma zinc ( Zn ) , copper ( Cu ) , selenium ( Se ) , urinary Zn , Cr , plasma thiobarbituric acid reactive substances ( TBARS ) , Cu-Zn superoxide dismutase ( SOD ) and Se glutathione peroxidase ( GPx ) in red blood cells , blood lipids and lipoproteins , HbA1C and fasting glucose were measured at the beginning of the study and after six months . Results : At the beginning of the study , more than 30 % of the subjects may have been Zn deficient with plasma Zn values less than 10.7 μmol/L , whereas levels of plasma Cu , Se and antioxidant RBC enzyme activities were in the normal ranges . Following supplementation , there were significant decreases of plasma TBARS in the Cr ( 13.6 % ) , Zn ( 13.6 % ) and Zn/Cr ( 18.2 % ) groups with no significant changes in the placebo group . The value for the TBARS of the control healthy Tunisian subjects was 2.08 ± 0.04 μmol/L and that of the Tunisian subjects with diabetes was 3.32 ± 0.05 μmol/L. This difference of 1.24 μmol/L between the control group and the subjects with diabetes was reduced from 36 % to 50 % in the three supplemented groups . Supplementation did not modify significantly HbA1C nor glucose homeostasis . No adverse effects  of Zn supplementation were observed on Cu status , HDL cholesterol nor interactions in Zn or Cr . Conclusions : These data suggest the potential beneficial antioxidant effects of the individual and combined supplementation of Zn and Cr in people with type 2 DM . These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes BACKGROUND Oxidative stress and dysregulation of antioxidant function play a pivotal role in the diabetic complications . METHODS Fifty-nine patients with diabetes were r and omly assigned into three groups . 1 ) PL group ( n = 19 ) : Polarized light ( PL ) was applied to neuropathic ulcers of diabetic foot twice daily for ten minutes in pulse regimen during three months . 2 ) QALA group ( n = 20 ) : Antioxidants ( 60 mg hydrosoluble CoQ10 , 100 mg alpha-lipoic acid ( ALA ) and 200 mg vitamin E ) were used in two daily doses for three months . 3 ) QALAPL group ( n = 20 ) : Patients used antioxidants along with PL applications . To test for differences in means , paired Student 's t-test ( before and after three months ) was used . RESULTS Three months application of PL significantly increased plasma concentrations of coenzyme Q10 , alpha-tocopherol , tau-tocopherol and beta-carotene , and decreased lactate dehydrogenase ( LDH ) activity . Supplementation with antioxidants decreased plasma lipid peroxides , increased concentration of CoQ10 and improved echocardiographic parameters . Simultaneous application of PL and antioxidants significantly stimulated plasma CoQ10 and alpha-tocopherol concentrations , decreased LDH activity and contributed to improvement in heart left ventricular function in diabetics . CONCLUSION Thus the data show that supportive therapy with PL along with the antioxidants hydrosoluble CoQ10 , alpha-lipoic acid and vitamin E is an effective way of controlling the complications of type 2 diabetes ( Tab . 7 , Fig. 2 , Ref . 44 ) Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads . The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis .  80 patients affected with a long term diabetic late syndrome were r and omised and arranged to 4 groups of n = 20 each . In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium ( sodium selenite ) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months . In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates . The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner . The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications Dietary supplementation is approximately a $ 30 billion industry in the United States , with more than 90 000 products on the market . In recent national surveys , 52 % of US adults reported use of at least 1 supplement product , and 10%reporteduseofatleast4suchproducts.1 Vitamins and minerals are among the most popular supplements and are taken by 48 % and 39 % of adults , respectively , typically to maintain health and prevent disease . Despite this enthusiasm , most r and omized clinical trials of vitamin and mineral supplements have not demonstrated clear benefits for primary or secondary prevention of chronic diseases not related to nutritional deficiency . Indeed , some trials suggest that micronutrient supplementation in amounts that exceed the recommended dietary allowance (RDA)—eg , high doses of beta carotene , folic acid , vitamin E , or selenium — may have harmful effects , including increased mortality , cancer , and hemorrhagic stroke.2 In this Viewpoint , we provide information to help clinicians address frequently asked questions about micronutrient supplements from patients , as well as promote appropriate use and curb inappropriate use of such supplements among generally healthy individuals . Importantly , clinicians should counsel their patients that such supplementation is not a substitute for a healthful and balanced diet and , in most cases , provides little if any benefit beyond that conferred by such a diet . Clinicians should also highlight the many advantages of obtaining vitamins and minerals from food instead of from supplements . Micronutrients in food are typically better absorbed by the body and are associated with fewer potential adverse effects.2,3 A healthful diet provides an array of nutritionally important substances in biologically optimal ratios as opposed to isolated compounds in highly concentrated form . Indeed , research shows that positive health outcomes are more strongly related to dietary patterns and specific food types than to individual micronutrient or nutrient intakes.3 Although routine micronutrient supplementation is not recommended for the general population , targeted supplementation may be warranted in high-risk groups for whom nutritional requirements may not be met through diet alone , including people at certain life stages and those with specific risk factors ( discussed in the next 3 sections and in the Box ) BACKGROUND Oxidative stress plays an important role in the development of diabetic cardiomyopathy . Alpha-lipoic acid ( ALA ) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction . AIM We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular ( LV ) dysfunction in children and adolescents with asymptomatic type 1 diabetes ( T1D ) . SUBJECTS AND METHODS Thirty T1D patients ( aged 10 - 14 ) were r and omized to receive insulin treatment ( n = 15 ) or insulin plus alpha-lipoic acid 300 mg twice daily ( n = 15 ) for four months . Age and sex matched healthy controls ( n = 15 ) were also included . Patients were evaluated with conventional 2-dimensional echocardiographic examination ( 2D ) , pulsed tissue Doppler ( PTD ) , and 2-dimensional longitudinal strain echocardiography ( 2DS ) before and after therapy .  Glutathione , malondialdhyde ( MDA ) , nitric oxide ( NO ) , tumor necrosis factor-alpha ( TNF-alpha ) , Fas lig and ( Fas-L ) , matrix metalloproteinase 2 ( MMP-2 ) , and troponin-I were determined and correlated to echocardiographic parameters . RESULTS Diabetic patients had significantly lower levels of glutathione and significantly higher MDA , NO , TNF-alpha , Fas-L , MMP-2 , and troponin-I levels than control subjects . The expression of transforming growth factor beta ( TGF-beta ) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients . Significant correlations of mitral e'/a ' ratio and left ventricular global peak systolic strain with glutathione , MDA , NO , TNF-alpha , and Fas-L were observed in diabetic patients . Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA , NO , TNF-alpha , Fas-L , MMP-2 , troponin-I levels , and TGF-beta gene expression . Moreover , alpha-lipoic acid significantly increased mitral e'/a ' ratio and left ventricular global peak systolic strain in diabetic patients . CONCLUSION These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes BACKGROUND Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity . However , few large trials in elderly people have been conducted that include end points for clinical variables . OBJECTIVE To determine the effects of long-term daily supplementation with trace elements ( zinc sulfate and selenium sulfide ) or vitamins ( beta carotene , ascorbic acid , and vitamin E ) on immunity and the incidence of infections in institutionalized elderly people . METHODS This r and omized , double-blind , placebo-controlled intervention study included 725 institutionalized elderly patients ( > 65 years ) from 25 geriatric centers in France . Patients received an oral daily supplement of nutritional doses of trace elements ( zinc and selenium sulfide ) or vitamins ( beta carotene , ascorbic acid , and vitamin E ) or a placebo within a 2 x 2 factorial design for 2 years . MAIN OUTCOME MEASURES Delayed-type hypersensitivity skin response , humoral response to influenza vaccine , and infectious morbidity and mortality . RESULTS Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year , during which there was no effect of any treatment on delayed-type hypersensitivity skin response . Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins , whereas the vitamin group had significantly lower antibody titers ( P<.05 ) . The number of patients without respiratory tract infections during the study was higher in groups that received trace elements ( P = .06 ) . Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections . Survival analysis for the 2 years did not show any differences between the 4 groups . CONCLUSIONS Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one OBJECTIVE The present study was design ed to assess the effect of magnesium plus zinc , vitamins C plus E , and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients . RESEARCH DESIGN AND METHODS In a r and omized , double-blind , placebo-controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months : group M ( n = 16 ) , 200 mg Mg and 30 mg Zn ; group V ( n = 18 ) , 200 mg vitamin C and 100 IU vitamin E ; group MV ( n = 17 ) , minerals plus vitamins ; and group P ( n = 18 ) , placebo .  Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity ( NAG ) in urine were determined at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . RESULTS Results indicate that after 3 months of supplementation , levels of urinary albumin excretion decreased in the V and MV groups ( P = 0.034 and P = 0.005 , respectively ) . Urinary NAG activity did not significantly change in any treatment groups . Levels of systolic , diastolic , and mean blood pressure significantly decreased in the MV group ( P = 0.008 , P = 0.017 , and P = 0.009 , respectively ) . Also , combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose ( P = 0.035 ) and malondialdehyde concentrations ( P = 0.004 ) and in increasing HDL cholesterol and apolipoprotein A1 levels ( P = 0.019 ) . There was no significant change in the levels of these parameters in the other three groups . CONCLUSIONS In conclusion , the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium , zinc , and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients Background Diabetes and vitamin D deficiency are global epidemics . Research ers have long been exploring the role of potentially modifiable factors to manage type 2 diabetes . We conducted a systematic review of prospect i ve studies and r and omized controlled trials that involved vitamin D supplementation and specifically intended to study glycemic outcomes related to type 2 diabetes . Methods Two authors independently search ed Medline and PubMed for longitudinal studies that had assessed the effect of vitamin D supplements on glycemic control , insulin resistance and beta-cell dysfunction in patients with diabetes . Results Seventeen r and omized control trials and seven longitudinal studies with a minimum follow-up of one month were included . Results of the various short-term studies ( follow up ≤ 3 months ) suggested that vitamin D supplementation had a positive impact on glycemic control and metabolic parameters such as insulin resistance and beta cell dysfunction . However , the evidence was weak due to the low method ological quality of the studies . There was no significant effect on HbA1c , beta cell function and insulin resistance in the long-term studies ( follow up > 3 months ) . There existed heterogeneity in the methodology of the studies , inclusion criteria , mode of supplementation of vitamin D and the duration of follow up . Conclusions Current evidence based on r and omized controlled trials and longitudinal studies do not support the notion that vitamin D supplementation can improve hyperglycemia , beta cell secretion or insulin sensitivity in patients with type 2 diabetes . Large-scale trials with proper study design , optimal vitamin D supplementation and longer follow up need to be conducted Chromium supplements are thought to be the second most commonly taken nutritional supplement , used by an estimated 10 million Americans ( 1 ) . Chromium is an essential element in humans , and deficiency is associated with the development of diabetes , which was first noted in patients receiving long-term parenteral nutrition before the advent of routine chromium supplementation  ( 2,3 ) . In these patients , diabetes resolved following chromium replacement ( 2–4 ) . The dietary requirement for chromium is controversial , with the recommended daily intake in the U.S. being 0.05–0.20 μg ( 5 ) . Chromium is abundant in the environment ; however , aside from the extreme situation of unsupplemented parenteral nutrition , it has proven difficult to ascertain any clinical effects , due solely to chromium deficiency . Despite these difficulties , chromium supplements are widely promoted in the complementary health industries . There are many studies examining the effects of various forms of chromium supplementation ( rev . in 6,7 ) . These studies utilized a variety of chromium formulations , varying doses , and patients with normal glucose tolerance , diabetes , or gestational diabetes . The outcomes have been inconsistent . Some studies showed no benefit , and other studies have shown inconsistent improvements in glucose , insulin resistance , and /or lipids . The paucity of data has prompted the National Institutes of Health to release a program announcement to address the issue : “ Chromium as an adjuvant therapy Oxidative stress plays a central role in the pathogenesis and progression of late microangiopathic complications ( diabetic nephropathy ) in diabetes mellitus . Previous studies suggested that treatment of diabetic patients with the antioxidant alpha-lipoic acid reduce oxidative stress and urinary albumin excretion . In this prospect i ve , open and non-r and omized study , the effect of alpha-lipoic acid on the progression of endothelial cell damage and the course of diabetic nephropathy , as assessed by measurement of plasma thrombomodulin and urinary albumin concentration ( UAC ) , was evaluated in 84 patients with diabetes mellitus over 18 months . Forty-nine patients ( 34 with Type 1 diabetes , 15 with Type 2 diabetes ) had no antioxidant treatment  and served as a control group . Thirty-five patients ( 20 with Type 1 diabetes , 15 with Type 2 diabetes ) were treated with 600 mg alpha-lipoic acid per day . Only patients with an urinary albumin concentration < 200 mg/l were included into the study . After 18 months of follow up , the plasma thrombomodulin level increased from 35.9+/-9.5 to 39.7+/-9.9 ng/ml ( P<0.05 ) in the control group . In the alpha-lipoic acid treated group the plasma thrombomodulin level decreased from 37.5+/-16.2 to 30.9+/-14.5 ng/ml ( P<0.01 ) . The UAC increased in patients without alpha-lipoic acid treatment from 21.2+/-29.5 to 36.9+/-60.6 ng/l ( P<0.05 ) , but was unchanged with alpha-lipoic acid . It is postulated that the significant decrease in plasma thrombomodulin and failure of UAC to increase observed in the alpha-lipoic acid treated group is due to antioxidative effects of alpha-lipoic acid , and if so that oxidative stress plays a central role in the pathogenesis of diabetic nephropathy . Furthermore , progression of the disease might be inhibited by antioxidant drugs . A placebo-controlled study is needed Context Research suggests that selenium supplements may improve glucose metabolism . Contribution The investigators examined the incidence of type 2 diabetes among participants in a clinical trial design ed to assess the effects of selenium supplementation on skin cancer . Participants r and omly assigned to receive selenium  were more likely to develop type 2 diabetes than were those assigned to placebo . Caution s Diabetes was a secondary outcome of the original trial . The diagnosis was self-reported , and most participants were older and white . Implication Long-term selenium supplementation appears to increase the risk for type 2 diabetes .  The Editors Insulin resistance , impaired glucose tolerance , and type 2 diabetes are all linked to oxidative stress , which may be the pathogenic mechanism that links these conditions to cardiovascular disease ( 1 ) . Observational epidemiologic studies show a protective association of dietary or plasma antioxidants against the development of type 2 diabetes ( 2 , 3 ) . However , the few clinical trials that have examined the efficacy of antioxidant supplementation in the prevention of type 2 diabetes or its complications have had negative results ( 46 ) . Experimental evidence from animal models suggests that supplementation with low doses of the antioxidant selenium may exert beneficial effects on glucose metabolism , possibly through many insulin-like actions , and may delay complications of diabetes . The effects of high-dose selenium supplements , however , are less clear ( 710 ) . Some studies in patients with diabetes suggest that selenium supplementation may help to prevent vascular complications ( 11 ) and that diabetic patients may be deficient in selenium relative to healthy persons ( 12 ) . Conversely , recent findings from the SU.VI.MAX ( Supplementation with Antioxidant Vitamins and Minerals ) study ( 13 ) showed no effect of supplementation with a combination of antioxidants , including selenium ( 100 g/d ) , on fasting plasma glucose levels after 7.5 years of follow-up . Because no r and omized , placebo-controlled clinical trials to date have tested the effect of long-term supplementation with selenium alone ( 200 g/d ) on the risk for type 2 diabetes , we examined the efficacy of selenium supplementation in preventing new-onset type 2 diabetes in the NPC ( Nutritional Prevention of Cancer ) trial , a r and omized , double-blind clinical trial design ed primarily to evaluate the efficacy of selenium supplementation for prevention of cancer ( 14 , 15 ) . Specifically , we assessed the incidence of type 2 diabetes as a secondary end point throughout the blinded phase of the trial ( 19831996 ) among participants who did not have type 2 diabetes at baseline ( n= 1202 ) . Methods Design and Participants The rationale , design , and methods of the NPC trial are described in detail elsewhere ( 14 ) . In brief , the NPC trial was a r and omized , double-blind , placebo-controlled study of 1312 participants who were recruited in 1983 to 1991 from 7 dermatology clinics in areas of low selenium consumption of the eastern United States . R and omization was blocked by time and stratified by clinic . Persons were eligible if they had a confirmed history of nonmelanoma skin cancer in the year before r and omization , had an estimated life expectancy of 5 years , and had no reported internal cancer in the previous 5 years . Participants with a history of clinical ly important liver or kidney disorders were excluded . Because the primary aim of the trial was to determine the effects of selenium supplementation on nonmelanoma skin cancer , we excluded nonwhite persons . This restriction served to control the effects of skin pigmentation on the risk for skin cancer recurrence . As a result , almost all participants in the NPC trial were non-Hispanic white persons ; about 1.4 % ( n= 18 ) of persons who were r and omly allocated were identified as Hispanic , and some persons were from other ethnic groups . Although recruitment was sex-neutral , about three quarters of the participants were male . Of the 1316 persons recruited , r and om assignment was successful for 1312 . At the end of the blinded treatment period on 1 February 1996 , no participant was lost to vital follow-up , generating a total of 9301 person-years of follow-up . Self-reported adherence indicated that 79.3 % of participants ( 80.3 % in the placebo group and 78.4 % in the selenium group ) adhered to the intervention ( 16 ) . This was corroborated by the fact that plasma selenium levels remained constant throughout the trial in the placebo group but were substantially higher in the selenium group ( Figure 1 ) . Figure 1 . Mean plasma selenium levels . We analyzed only participants with a valid baseline selenium value obtained within 4 days from the date of r and omization ( 1250 of 1312 participants ) , a decision that is consistent with previously published studies from the NPC trial ( 1517 ) . Baseline characteristics of the total NPC cohort of 1312 participants and the sub sample of 1250 participants with valid baseline selenium levels did not statistically significantly differ ( 17 ) , and our findings did not change substantially when analyses were exp and ed to include all 1312 participants ( data not reported ) . We focus on the 1202 participants who did not have type 2 diabetes at baseline ( 600 selenium recipients and 602 placebo recipients ) . Ascertainment of prevalent type 2 diabetes at baseline was based on a self-reported diagnosis of type 2 diabetes before r and omization , with subsequent evaluation of medical records ( 48 cases [ 21 in the selenium group and 27 in the placebo group ] ) . Figure 2 shows the flow diagram of the NPC participants included in our analysis . Figure 2 . Flow diagram of the Nutritional Prevention of Cancer Trial , 19831996 . Clinical Examination and Laboratory Methods The intervention agent was 200 g of selenium daily , supplied in a 0.5-g , high-selenium baker 's yeast tablet provided by Nutrition 21 ( La Jolla , California ) through 1995 and by Cypress Systems ( Fresno , California ) thereafter . The placebo group received a tablet containing yeast only . Selenium and placebo pills were coated with titanium oxide to ensure identical appearance and smell . Each patient was assigned a unique sequential treatment number . Treatment group assignment was made central ly by using sealed identical pill bottles that were distributed at the clinic . The coordinating center held all treatment information in blinded form ( 14 ) . The selenium content of each batch of pills was determined in the laboratories of Dr. Combs and of I.S. Palmer , MD ( South Dakota State University , Brookings , South Dakota ) , by the diaminonapthalene fluorometric procedure after nitricperchloric acid digestion ( 18 ) . Plasma selenium level was determined in the laboratory of Dr. Combs by using an automated electrothermal atomic absorption spectrophotometer ( Perkin Elmer 3030 , Perkin-Elmer , Norwalk , Connecticut ) equipped with an electrodeless discharge lamp and automatic Zeeman-effect background correction . Quality control included multiple aliquots of human plasma as external control sample s. A coefficient of variation less than 7 % ( for duplicate analyses ) was the criterion for acceptance ( 19 ) . Participants visited their respective clinics biannually to provide blood sample s and report new illnesses and medications . Patient medical records from both study and non study visits were periodically review ed to ensure completeness and accuracy . At the baseline interview , data were collected on sociodemographic , anthropometric , and behavioral characteristics , including education ( 0 to 18 years ) , body mass index ( BMI ) , use of vitamin supplements , alcohol consumption ( drinks consumed per day ) , smoking status ( never , former , or current ) , and pack-years of smoking . For participants who became inactive , annual monitoring was attempted by using the National Death Index and ChoicePoint Services ( formerly Equifax , Atlanta , Georgia ) to determine vital status and identify diagnoses of new illnesses . Ascertainment of Type 2 Diabetes and Follow-up Participants who had a new diagnosis of type 2 diabetes during the blinded phase of the trial ( 15 September 1983 to 1 February 1996 ) were noted . The initial report of diabetes came from 3 sources : self-report during the clinical interview , reported use of drugs for diabetes , and reports in medical record documents . Medical record requests were then sent to the primary physicians for every patient with a report . This process of requesting and review ing documentation was done in a blinded manner . About 92 % of these reports , regardless of source , were corroborated with medical record documentation , as determined by registered nurse review ers . Person-years of follow-up were accrued from the date of r and omization as the start date to the date of an incident case of type 2 diabetes , the date of death , or the end of the blinded period of the trial . Statistical Analysis For continuous and categorical variables , we used t tests and chi-square tests , respectively , to determine the statistical significance of any difference in the distribution of baseline variables between treatment groups . Cumulative incidence curves of type 2 diabetes by treatment group were constructed by comparing NelsonAalen cumulative hazard function estimates that were calculated at different time points of the trial and by using the 2-sided log-rank test ( 20 ) . In unadjusted analyses , incidence data were statistically analyzed by calculating relative risks as the ratios of the incidence density for the treatment groups , with corresponding 95 % CIs . P values were derived from log-rank tests . In adjusted analyses , hazard ratios and 95 % CIs were calculated by using the Cox proportional hazard model , which allowed adjustment for age , BMI ( continuous variable ) , sex , and smoking status at baseline as covariates . We decided a priori to adjust for these diabetes risk factors regardless of whether they differed between treatment groups . Tests of proportional hazards assumptions were based on DESIGN Placebo for 3 months , followed by 30 mg/day zinc gluconate in identical capsules . SETTING Diabetic out patients clinic at the University Hospital , Grenoble . SUBJECTS Diabetic patients cared for type I diabetes mellitus . 22 patients began the study , 4 dropped out . 10 patients suffered of an early retinopathy , 8 patients had no retinopathy . INTERVENTIONS In this order : T0 biological measurements , 3 months placebo treatment , T1 biological measurements , 3 months zinc gluconate treatment , T2 biological measurements . Plasma Zn , Cu , Se , thiobarbituric acid reactants and antioxidant enzymes were measured [ plasma and red glutathione peroxidase ( Se-GPx ) , red cell superoxide dismutase ( Cu-Zn-SOD ) ] . RESULTS Lower plasma zinc level in the two groups . An increase in zinc level was observed and was more important in diabetic patients with no retinopathy ( P = 0.05 ) . The thiobarbituric acid reactants were above the reference values in all the patients , and were decreased at T2 ( P < 0.05 ) . Increase of GPx activity after zinc supplementation in patients with retinopathy . CONCLUSIONS Zinc deficiency in insulin-dependent diabetic patients is corrected by a zinc supplementation . Moreover this supplementation decreases lipid peroxidation . The effects of zinc are different in diabetic patients with or without retinopathy . The increase in Se-GPx activity observed in patients with retinopathy could be linked to the protective effect of zinc on the protein itself PURPOSE The Age-Related Eye Disease Study ( AREDS ) demonstrated beneficial effects of oral supplementation with antioxidant vitamins and minerals on the development of advanced age-related macular degeneration ( AMD ) in persons with at least intermediate AMD ( bilateral large drusen with or without pigment changes ) . Observational data suggest that other oral nutrient supplements might further reduce the risk of progression to advanced AMD . The primary purpose of the Age-Related Eye Disease Study 2 ( AREDS2 ) is to evaluate the efficacy and safety of lutein plus zeaxanthin ( L+Z ) and /or ω-3 long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation in reducing the risk of developing advanced AMD . The study also assesses the reduction in zinc and the omission of β-carotene from original AREDS formulation . DESIGN Multicenter , phase III , r and omized , controlled clinical trial . PARTICIPANTS Persons aged 50 to 85 with bilateral intermediate AMD or advanced AMD in 1 eye . METHODS All participants were r and omly assigned to placebo ( n = 1012 ) , L+Z ( 10 mg/2 mg ; n = 1044 ) , ω-3 LCPUFAs ( eicosapentaenoic acid + docosahexaenoic acid [ 650 mg/350 mg ] ; n = 1069 ) , or the combination of L+Z and ω-3 LCPUFAs ( n = 1078 ) . All participants were offered a secondary r and omization to 1 of 4 variations of the original AREDS formulation keeping vitamins C ( 500 mg ) and E ( 400 IU ) and copper ( 2 mg ) unchanged while varying zinc and β-carotene as follows : Zinc remains at the original level ( 80 mg ) , lower only zinc to 25 mg , omit β-carotene only , or lower zinc to 25 mg and omit β-carotene . MAIN OUTCOME MEASURES Progression to advanced AMD determined by central ized grading of annual fundus photographs . RESULTS We enrolled 4203 participants at 82 clinical centers located in the United States . Population characteristics at baseline were as follows : Mean age , 74 years ; 57 % female ; 97 % white ; 7 % current smokers ; 19 % with prior cardiovascular disease ; and 44 % and 50 % taking statin-class cholesterol-lowering drugs and aspirin , respectively . Ocular characteristics include 59 % with bilateral large drusen , 32 % with advanced AMD in 1 eye and mean visual acuity of 20/32 in eyes without advanced AMD . CONCLUSIONS This report presents the AREDS2 study design and the participants ' baseline demographic and ocular characteristics Introduction Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring . A wealth of observational studies have reported on both obstetric outcomes and complications , including pre-eclampsia , gestational diabetes , mode and timing of delivery . Many foetal and childhood outcomes are also linked to vitamin D status , including measures of foetal size , body composition and skeletal mineralization , in addition to later childhood outcomes , such as asthma . Sources of data Synthesis of systematic and narrative review s. Areas of agreement and controversy The findings are generally inconsistent in most areas , and , at present , there is a lack of data from high- quality intervention studies to confirm a causal role for vitamin D in these outcomes . In most areas , the evidence tends towards maternal vitamin D being of overall benefit , but often does not reach statistical significance in meta-analyses . Growing points and areas timely for developing research The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia ; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily . High- quality r and omized placebo-controlled trials , such as the UK-based MAVIDOS trial , will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes Knowledge about the impact of maternal food and micronutrient supplementation on infant micronutrient status is limited . We examined the effect of maternal food and micronutrient supplementation on infant micronutrient status in the Maternal and Infant Nutrition Interventions in Matlab Trial . Pregnant women ( n = 4436 ) were r and omized to Early or Usual promotion of enrollment in a food supplementation program . In addition , they were r and omly allocated to 1 of the following 3 types of daily micronutrient supplements provided from wk 14 of gestation to 3 mo postpartum : 1 ) folic acid and 30 mg iron ( Fe30Fol ) ; 2 ) folic acid and 60 mg iron ; or 3 ) a multiple micronutrient including folic acid and 30 mg iron ( MMS ) . At 6 mo , infant blood sample s ( n = 1066 ) were collected and analyzed for hemoglobin and plasma ferritin , zinc , retinol , vitamin B-12 , and folate . The vitamin B-12 concentration differed between the micronutrient supplementation groups ( P = 0.049 ) . The prevalence of vitamin B-12 deficiency was lower in the MMS group ( 26.1 % ) than in the Fe30Fol group ( 36.5 % ) ( P = 0.003 ) . The prevalence of zinc deficiency was lower in the Usual food supplementation group ( 54.1 % ) than in the Early group ( 60.2 % ) ( P = 0.046 ) . There were no other differential effects according to food or micronutrient supplementation groups . We conclude that maternal multiple micronutrient supplementation may have a beneficial effect on vitamin B-12 status in infancy OBJECTIVE Best disease is a slowly progressive macular dystrophy that typically has an onset in early childhood . Multiple lines of evidence suggest that dietary docosahexaenoic acid ( DHA ) protects against the development of macular degeneration . Our trial tested the effect of an oral supplement of DHA on visual function in patients with Best disease . DESIGN Double-masked , r and omized , placebo-controlled , crossover clinical trial . PARTICIPANTS Eight patients with Best disease . METHODS Patients were given either an oral supplement of DHA ( 20 mg/kg daily ) or placebo . Primary outcome measures were the multifocal electroretinogram ( mfERG ) and electro-oculogram ( EOG ) . Plasma DHA was tracked along with visual acuity ( Early Treatment Diabetic Retinopathy Study chart ) , VF-14 scores , and Humphrey visual fields . RESULTS All 8 patients had increased plasma DHA levels ( 2 - 3 fold ) during periods of DHA supplementation compared with periods without supplementation . Differences in visual acuity , VF-14 scores , and EOG Arden ratios during periods with and without DHA supplementation were all statistically insignificant . A positive correlation was found between the plasma concentration of DHA and mfERG amplitudes , but amplitude changes during the treatment periods were not significant . A carryover effect of DHA supplementation was a confounding error . CONCLUSIONS Our pilot trial of DHA supplementation in 8 patients with Best disease did not demonstrate an improvement in macular function . An exp and ed trial would be needed to examine the full effects of DHA supplementation on visual function in Best disease BACKGROUND Pre clinical studies have shown that the combination of chromium picolinate and biotin significantly enhances glucose uptake in skeletal muscle cells and enhances glucose disposal . The present pilot study was conducted to determine if supplementation with chromium picolinate and biotin can improve glycemic control in patients with type 2 diabetes mellitus with suboptimal glycemic control despite use of oral antihyperglycemic agents . METHODS Forty-three subjects with impaired glycemic control ( 2-h glucose > 200 mg/dL ; glycated hemoglobin > or=7 % ) , despite treatments with oral antihyperglycemic agents  , were r and omized to receive 600 microg of chromium as chromium picolinate and biotin ( 2 mg/day ) ( Diachrome ( , Nutrition 21 , Inc. , Purchase , NY ) in addition to their pre study oral antihyperglycemic agent therapy . Measurements of glycemic control and blood lipids were taken at baseline and after 4 weeks . RESULTS After 4 weeks , there was a significantly greater reduction in the total area under the curve for glucose during the 2-h oral glucose tolerance test for the treatment group ( mean change -9.7 % ) compared with the placebo group ( mean change + 5.1 % , P < 0.03 ) . Significantly greater reductions were also seen in fructosamine ( P < 0.03 ) , triglycerides ( P < 0.02 ) , and triglycerides/ high-density lipoprotein cholesterol ratio ( P < 0.05 ) in the treatment group . No significant adverse events were attributed to chromium picolinate and biotin supplementation . CONCLUSIONS This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements .  Chromium picolinate/ biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism Background Despite Australia ’s sunny climate , low vitamin D levels are increasingly prevalent . Sun exposure is limited by long working hours , an increase in time spent indoors , and sun protection practice s , and there is limited dietary vitamin D fortification . While the importance of vitamin D for bone mineralization is well known , its role as a protective agent against chronic diseases , such as type 2 diabetes and cardiovascular disease , is less understood . Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion , mainly via its anti-inflammatory properties , thereby decreasing the risk of development and progression of type 2 diabetes . The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , obtained through vitamin D supplementation , will increase insulin sensitivity and insulin secretion . A secondary aim is to determine whether these relationships are mediated by a reduction in underlying sub clinical inflammation associated with obesity . Methods / Design Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old , with low vitamin D levels ( 25(OH)D < 50 nmol/l ) , will be r and omly assigned to intervention or placebo . At baseline , participants will undergo a medical review and anthropometric measurements , including dual X-ray absorptiometry , an intravenous glucose tolerance test , muscle and fat biopsies , a hyperinsulinemic euglycemic clamp  , and question naires assessing diet , physical activity , sun exposure , back and knee pain , and depression . The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D ( cholecalciferol ) daily , while the placebo group will receive apparently identical capsules , both for a period of 16 weeks . All measurements will be repeated at follow-up , with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group . Secondary outcome measures will compare changes in anthropometry , cardiovascular risk factors , and inflammatory markers . Discussion The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms , which are relevant for the prevention and management of type 2 diabetes . Trial registration Clinical trials.gov ID : NCT02112721 INTRODUCTION Increased oxidative stress , inflammation , and malnutrition are present in hemodialysis patients and these factors exacerbate cardiovascular comorbidities . Vitamin E and alpha-lipoic acid ( ALA ) may have a protective role against cardiovascular disease risk factors via anti-oxidative and anti-inflammatory properties . The aim of this study was to evaluate the effect of ALA and vitamin E administration ( alone or combined ) on hemodialysis-induced stress oxidation , inflammation , and malnutrition . MATERIAL S AND METHODS In a r and omized placebo-controlled trial , we examined the effects of 2-month supplementation by vitamin E and ALA ( alone or combined ) on biomarkers of lipid peroxidation ( malondialdehyde ) , inflammation ( high-sensitivity C-Reactive protein and interleukin-6 ) , and malnutrition ( Subjective Global Assessment and body mass index ) in 85 hemodialysis patients receiving ALA ( 600 mg ) , vitamin E ( 400 IU ) , ALA and vitamin E , and placebo .  RESULTS After supplementation , no significant changes were observed in malondialdehyde level ; however , there was a decrease in the ALA and vitamin E group during the period of the study . Also , a nonsignificant decrease was seen in the high-sensitivity C-Reactive protein concentration of the interventional groups . Supplementation of vitamin E with and without ALA significantly reduced interleukin-6 concentration . A significant improvement was observed in malnutrition status of all groups . CONCLUSIONS Vitamin E and ALA supplementation , especially their combination , might improve inflammation and malnutrition status , which suggest it as a potential preventive strategy against CVD among end-stage renal disease patients Background Osteoporosis is a major health problem , and the economic burden is expected to rise due to an increase in life expectancy throughout the world . Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk . As vitamin B12 and folate intake and status play a large role in homocysteine metabolism , it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration . Methods / Design The B-PROOF ( B-Vitamins for the PRevention Of Osteoporotic Fractures ) study is a r and omized double-blind placebo-controlled trial . The intervention comprises a period of two years , and includes 2919 subjects , aged 65 years and older , independently living or institutionalized , with an elevated homocysteine concentration ( ≥ 12 μmol/L ) . One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet . In both tablets 15 μg ( 600 IU ) vitamin D is included . The primary outcome of the study is osteoporotic fractures . Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers , physical performance and physical activity including falls , nutritional intake and status , cognitive function , depression , genetics and quality of life . This large multi-center project is carried out by a consortium from the Erasmus MC ( Rotterdam , the Netherl and s ) , VUmc ( Amsterdam , the Netherl and s ) and Wageningen University , ( Wageningen , the Netherl and s ) , the latter acting as coordinator . Discussion To our best knowledge , the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population . We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013 . The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures . Trial Registration The B-PROOF study is registered with the Netherl and s Trial ( NTR NTR1333 ) and with Clinical Trials.gov ( NCT00696514 ) OBJECTIVE To investigate if a-keto/amino acid supplemented low protein diet can slow down the progression of diabetic nephrophathy in comparison with non-supplemented diabetes diet . METHODS A prospect i ve , r and omized , controlled clinical study was conducted . Twenty three cases of type 2 diabetic nephropathy in IV stage were r and omly divided into alpha-keto/amino acid supplemented diet group ( trial group ) and conventional diabetes diet group ( control group ) , The treatment duration was 52 weeks . 24 h urine protein was measured at 0 , 12 , 20 , 36 and 52 weeks . Before and after the 52 weeks treatment , all the patients received the measurement of glomerular filtration rate ( GFR ) , blood glucose , blood lipids , inflammatory markers , as well as nutritional status . RESULTS After the treatment for 20 , 36 , 52 weeks , mean 24 h urine protein decreased significantly in trial groups ( P < 0.05 ) , and 24 h urine protein in trial group were significantly decreased ( P < 0.05 ) compared with control group in 20 weeks after treatment . Either in trial group or in control group , GFR remained relatively stable during the observation period . Nutrition status , inflammatory markers , and serum calcium , phosphorus levels between the two groups were no significantly difference . The adverse events experienced by the patients in trial group were similar and consistent with the patients underlying renal diseases . CONCLUSION Alpha-keto/amino acid can reduce proteinuria more effectively , while improve renal function and nutritional status in diabetic nephropathy patients with well-toleration Background Besides the classical role of vitamin D on calcium and bone homeostasis , vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus . However , it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus . There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control . The objective of this study is to investigate the effect of vitamin D supplementation on glycaemic control and quality of life in patients with type 2 diabetes mellitus . Methods / design In a r and omised double-blind placebo-controlled trial conducted in five general practice s in the Netherl and s three hundred patients with type 2 diabetes mellitus treated with lifestyle advises or metformin or sulphonylurea-derivatives are r and omised to receive either placebo or 50,000 IU Vitamin D3 at monthly intervals . The primary outcome measure is the change in glycated haemoglobin level between baseline and six months . Secondary outcome measures include blood pressure , anthropometric parameters , lipid profile , insulin resistance , quality of life , advanced glycation end products and safety profiles . Quality of life will be measured by The Short Form ( SF-36 ) Health Survey question naire . Advanced glycation end products are measured by an AGE-reader . Discussion This trial will be the first study exploring the effect of vitamin D supplementation on both glycaemic control and quality of life in patients with type 2 diabetes mellitus . Our findings will contribute to the knowledge of the relationship between vitamin D status and insulin resistance in patients with type 2 diabetes mellitus . Trial registration The Netherl and s trial register : BACKGROUND Previously we showed that women in rural Nepal experience multiple micronutrient deficiencies in early pregnancy . OBJECTIVE This study examined the effects of daily antenatal micronutrient supplementation on changes in the biochemical status of several micronutrients during pregnancy . DESIGN In Nepal , we conducted a r and omized controlled trial in which 4 combinations of micronutrients ( folic acid , folic acid + iron , folic acid + iron + zinc , and a multiple micronutrient supplement containing folic acid , iron , zinc , and 11 other nutrients ) plus vitamin A , or vitamin A alone as a control , were given daily during pregnancy . In a sub sample of subjects ( n = 740 ) , blood was collected both before supplementation and at approximately 32 wk of gestation . RESULTS In the control group , serum concentrations of zinc , riboflavin , and vitamins B-12 and B-6 decreased , whereas those of copper and alpha-tocopherol increased , from the first to the third trimester . Concentrations of serum folate , 25-hydroxyvitamin D , and undercarboxylated prothrombin remained unchanged . Supplementation with folic acid alone or folic acid + iron decreased folate deficiency . However , the addition of zinc failed to increase serum folate , which suggests a negative inhibition ; multiple micronutrient supplementation increased serum folate .  Folic acid + iron + zinc failed to improve zinc status but reduced sub clinical infection .  Multiple micronutrient supplementation decreased the prevalence of serum riboflavin , vitamin B-6 , vitamin B-12 , folate , and vitamin D deficiencies but had no effect on infection . CONCLUSIONS In rural Nepal , antenatal supplementation with multiple micronutrients can ameliorate , to some extent , the burden of deficiency . The implication s of such biochemical improvements in the absence of functional and health benefits remain unclear OBJECTIVE The purpose of this study was to prospect ively examine the association between vitamin D and calcium intake and risk of type 2 diabetes .  RESEARCH DESIGN AND METHODS In the Nurses ' Health Study , we followed 83,779 women who had no history of diabetes , cardiovascular disease , or cancer at baseline for the development of type 2 diabetes .  Vitamin D and calcium intake from diet and supplements was assessed every 2 - 4 years . During 20 years of follow-up , we documented 4,843 incident cases of type 2 diabetes . RESULTS After adjusting for multiple potential confounders , there was no association between total vitamin D intake and type 2 diabetes . However , the relative risk ( RR ) of type 2 diabetes was 0.87 ( 95 % CI 0.75 - 1.00 ; P for trend = 0.04 ) comparing the highest with the lowest category of vitamin D intake from supplements . The multivariate RRs of type 2 diabetes were 0.79 ( 0.70 - 0.90 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from all sources and 0.82 ( 0.72 - 0.92 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from supplements . A combined daily intake of > 1,200 mg calcium and > 800 IU vitamin D was associated with a 33 % lower risk of type 2 diabetes with RR of 0.67 ( 0.49 - 0.90 ) compared with an intake of < 600 mg and 400 IU calcium and vitamin D , respectively . CONCLUSIONS The results of this large prospect i ve study suggest a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes BACKGROUND Vitamin E isomers may protect against atherosclerosis . The aim of this study was to compare the effects of supplementation with either alpha-tocopherol ( alphaT ) or mixed tocopherols rich in gamma-tocopherol ( gammaT ) on markers of oxidative stress and inflammation in patients with type 2 diabetes . METHODS In a double-blind , placebo-controlled trial , 55 patients with type 2 diabetes were r and omly assigned to receive ( 500 mg/day ) ( a ) alphaT , ( b ) mixed tocopherols , or ( c ) placebo for 6 weeks . Cellular tocopherols , plasma and urine F(2)-isoprostanes , erythrocyte antioxidant enzyme activities , plasma inflammatory markers , and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation . RESULTS Neutrophil alphaT and gammaT increased ( both P < 0.001 ) with mixed tocopherol supplementation , whereas alphaT ( P < 0.001 ) increased and gammaT decreased ( P < 0.005 ) after alphaT supplementation . Both alphaT and mixed tocopherol supplementation result ed in reduced plasma F(2)-isoprostanes ( P < 0.001 and P = 0.001 , respectively ) but did not affect 24-h urinary F(2)-isoprostanes or erythrocyte antioxidant enzyme activities . Neither alphaT nor mixed tocopherol supplementation affected plasma C-reactive protein , interleukin 6 , tumor necrosis factor-alpha , or monocyte chemoattractant protein-1 . Stimulated neutrophil leukotriene B(4 ) production decreased significantly in the mixed tocopherol group ( P = 0.02 ) but not in the alphaT group ( P = 0.15 ) . CONCLUSIONS The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes . In population s with well-controlled type 2 diabetes , supplementation with either alphaT or mixed tocopherols rich in gammaT is unlikely to confer further benefits in reducing inflammation Aims : The aim was to evaluate circulating levels of reactive oxygen species ( ROS ) and changes in central macular thickness ( CMT ) in patients with nonproliferative diabetic retinopathy ( NPDR ) after antioxidant supplementation . Material s and Methods : A total of 68 patients ( 68 eyes ) with NPDR were enrolled . Patients were r and omly divided into two groups : Treated with antioxidant supplement ( Group A ) and untreated control group ( Group B ) . Each tablet , for oral administration , containing pycnogenol 50 mg , Vitamin E 30 mg and coenzyme Q10 20 mg .  CMT and free oxygen radical test ( FORT )  were analyzed at baseline ( T0 ) , 3 ( T1 ) and 6 ( T2 ) months in both groups . Results : In Group A , FORT levels and CMT were significantly reduced over time ( P < 0.001 for both ) . In Group B , FORT levels were increased ( P < 0.001 ) and CMT did not vary significantly ( P = 0.81 ) over 3 time points . Conclusions : This is the first study showing the reduction of ROS levels in patients with NPDR thanks to antioxidant therapy . Moreover , our findings have suggested also an influence on retinal thickness We studied the macular pigment ocular density ( MPOD ) in patients with early age macular degeneration ( AMD ) before and 1 year after nutritional supplementation with lutein and docosahexaenoic acid ( DHA ) .  Forty-four patients with AMD were r and omly divided into two groups that received placebo ( n = 21 ) or a nutritional supplement ( n = 23 , 12 mg of lutein and 280 mg of DHA daily ) . Heterochromatic flicker photometry was used to determine the MPOD . At baseline , the MPOD in AMD patients with placebo was 0.286 ± 0.017 meanwhile in AMD patients with supplementation it was 0.291 ± 0.016 . One year later , the mean MPOD had increased by 0.059 in the placebo group and by 0.162 in patients receiving lutein and DHA . This difference between groups was significant ( p < 0.05 ) . Lutein and DHA supplementation is effective in increasing the MPOD and may aid in prevention of age related macular degeneration Summary : In patients with Crohn 's disease ( CD ) , malnutrition is frequently observed and is generally accepted to be an important issue . The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants ( AO ) or n‐3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue , respectively , in patients with long‐st and ing CD currently in remission . In a r and omized , double‐blind placebo‐controlled study , CD patients received either placebo , AO , or n‐3 fatty acids plus AO for 3 months in addition to their regular diet . In all , 25/37 CD patients completed the study . AO status was assessed by blood biochemical parameters . A statistical per‐ protocol analysis was performed . Serum concentrations of selenium , vitamin C , and vitamin E , the activity of superoxide dismutase and total antioxidant status were significantly ( p < 0.05 ) increased after AO supplementation . Furthermore , compared with controls , serum concentrations of & bgr;‐carotene , selenium , and vitamin C and the activity of glutathione peroxidase ( GPx ) were significantly ( p < 0.05 ) lower before supplemention ; however , after AO supplementation these levels were not significantly different from controls ( except for GPx ) . N‐3 fatty acids plus AO supplementation significantly ( p < 0.05 ) decreased the proportion of arachidonic acid , and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue . Supplementation with antioxidants improved antioxidant status in patients with CD in remission . In addition , supplementation with n‐3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile , which may lead to the production of eicosanoids with attenuated proinflammatory activity . This study indicates that an immunomodulating formula containing n‐3 fatty acids and /or AO may have the potential to play a role in the treatment of CD AIM OF THE STUDY To evaluate with an open-label study the efficacy and safety of a complex of nutritional supplements with antioxidant activity ( L-carnitine , acetyl-L-carnitine , fructose , citric acid , selenium , coenzyme Q10 , zinc , ascorbic acid , cyanocobalamin , folic acid ) in primary infertile patients with idiopathic astenoteratozoospermia . METHODS The study was conducted in a population of 114 infertile men ( 96 completed the study ) diagnosed with idiopathic astenoteratozoospermia since at least 18 months . Patients orally received a formulation ( Proxeed - Sigma-Tau ) containing L-carnitine 145 mg , acetyl-L-carnitine 64 mg , fructose 250 mg , citric acid 50 mg , selenium 50 mcg , coenzyme Q10 20 mg , zinc 10 mg , ascorbic acid 90 mg , cyanocobalamin 1.5 mcg , folic acid 200 mcg in combination once a day for 4 months . RESULTS At the end of study , the mean sperm progressive motility showed a statistically significant increase from 18.3 + /- 3.8 to 42.1 + /- 5.5 . Sixteen patients achieved pregnancy during the study . No significant improvement were observed for sperm density and rate of morphologically normal forms . The treatment was well tolerated . CONCLUSIONS Carnitines in association with others functional substances can improve the most important parameters of sperm quality To evaluate the protective effects of α-lipoic acid on the kidneys of Goto-Kakisaki ( GK ) diabetic rats , ten GK diabetic rats were r and omly divided into a diabetic control group and a lipoic acid-treated diabetic group with α-lipoic acid 35 mg·Kg−1 intraperitoneal injections . Four healthy Wistar rats served as normal controls . Malonaldehyde ( MDA ) , ascorbic acid ( vitamin C ) , vitamin E , glutathione ( GSH ) and superoxide dismutase ( SOD ) levels in renal homogenate , and urine protein excretion were measured . The expression of mRNA for NF-κB , NADPH oxidase subunits p22phox and p47phox in renal tissue was examined by realtime PCR . Pathological changes in renal tissue were evaluated by light and electron microscopy . There were significant increases in urine protein excretion , MDA levels and the expression of mRNA of NF-κB , p22phox and p47phox , and significant decreases in GSH , SOD , vitamin C and vitamin E levels in the diabetic control group compared with the normal control group . Pathological changes of renal tissue were more progressive in the diabetic control group than in the normal control group . All the parameters above were improved in the α-lipoic acid-treated diabetic group . Oxidative stress is increased in the kidney of type 2 diabetic GK rats . It is associated with the progression of diabetic nephropathy . α-lipoic acid can protect renal function in diabetic rats via its antioxidant activity Background : Diabetes mellitus ( DM ) and vitamin D deficiency are major health concerns around the world . Evidence suggests a possible role of vitamin D in improvement of insulin secretion and sensitivity . Objectives : We assessed whether vitamin D supplementation could be used in vitamin D deficient-type II diabetes to improve glucose metabolism , components of metabolic syndrome ( MetS ) and specific inflammatory biomarkers . Patients and Methods : A double blind , r and omized clinical trial was conducted in King Khalid University Hospital , Saudi Arabia to evaluate the effect of cholecalciferol supplementation on glycemic control , MetS components and specific inflammatory biomarkers including tumor necrosis factor-alpha ( TNF-α ) , Interleukin ( IL-6 ) , leptin , adiponectin and vascular cell adhesion molecule-1 ( VCAM-1 ) . Twenty-two patients with type II diabetes with insulin resistance , glycated hemoglobin ( HbA1c ) ≥ 6 ( 42 mmol/mol ) and serum 25(OH)D < 50 nmol/L were r and omized using a computer program to receive either supplementation with cholecalciferol ( 5000 IU/day ) or placebo for 12 weeks . The primary outcome was change in HbA1c levels from baseline . Results : Median [ IQR ] 25(OH)D levels increased significantly in the vitamin D group as 58.1 [ 48 , 67.3 ] nmol/L ( P = 0.002 ) . There was no significant difference in the change of HbA1c between the groups ( P = 0.5 ) with a decrease of -0.1 % [ -1 , 0.5 ] in the vitamin D group and an increase of 0.15 % [ 0.1 , 0.2 ] in the placebo group . A significant improvement was observed in the homeostasis model of assessment of β-cell activity ( HOMA-%B ) ( P = 0.03 ) with vitamin D supplementation compared to baseline . Conclusions : Vitamin D repletion for 12 weeks increased serum vitamin D concentrations and improved β-cell activity in vitamin D-deficient type II diabetes with no significant changes in HbA1c or insulin sensitivity Zinc and folic acid nutritional status was evaluated in 74 low-income pregnant adolescents ranging from 13 to 18 years of age who received prenatal care at the Evangelina Rosa Maternity Hospital in Teresina , Piau State , Brazil . In order to evaluate the effects of different supplementation regimens on nutritional status , the adolescents were distributed into five groups . Groups I and II received equal amounts of folic acid ( 250 micro;g ) and different doses of iron ( ferrous sulfate ) , 120 and 80 mg , respectively . Groups III and IV received equal amounts of folic acid ( 250 micro;g ) associated with zinc sulfate and iron at doses of 120 and 80 mg , respectively , while group V received only 120 mg of iron ( routine dosage ) . There was a reduction in the zinc plasma concentration , and this decline was significant only in those groups which did not receive zinc supplementation . In relation to combination iron/folic acid and iron/folic acid/zinc  , an excellent response was observed for folic acid , and this effect was larger in the groups that received folic acid combined with zinc , suggesting a possible role for zinc in folic acid metabolism
The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors .
A majority of the trials found a positive effect of chromium on fasting plasma glucose .
Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures , but only when combined with soy proteins .
Vitamin E is reported to reduce oxidative stress at levels of 200 mg day(-1 ) or more
The role of nutritional supplementation is of increasing interest with regard to ocular disease .
R and omised controlled trials have demonstrated the effectiveness of supplementation for age-related macular degeneration , and formulations are now being developed for use by people with diabetes and diabetic retinopathy .
The aim of this review was to synthesis e the evidence for use of nutritional supplementation in type 2 diabetes .
The potential role of alpha-lipoic acid , chromium , folic acid , isoflavones , magnesium , Pycnogenol , selenium , vitamin C , vitamin E , and zinc in the treatment of type 2 diabetes is discussed .