Showing papers on "B vitamins published in 2008"

Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study.

Abstract: Aims/hypothesis Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years.

Nicotinic Acid, Nicotinamide, and Nicotinamide Riboside: A Molecular Evaluation of NAD+ Precursor Vitamins in Human Nutrition

Abstract: Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.

Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial.

Abstract: Context Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials. Objective To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD. Design, Setting, and Participants Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005. Intervention Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12. Main Outcome Measures A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality. Results Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10 000 person-years vs 219.2/10 000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10 000 person-years vs 39.5/10 000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10 000 person-years vs 36.8/10 000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10 000 person-years vs 49.6/10 000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P Conclusion After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering. Trial Registration clinicaltrials.gov Identifier: NCT00000541

High-Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Controlled Trial

Abstract: Context Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B 6 and B 12 . Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. Objective To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. Design, Setting, and Patients A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B 6 , and vitamin B 12 supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B 12 , and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. Intervention Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B 6 , 1 mg/d of vitamin B 12 ] and 40% treated with identical placebo); duration of treatment was 18 months. Main Outcome Measure Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Results A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], −2.42 [3.35] in active treatment group vs −0.86 [2.59] in placebo group; P Conclusion This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. Trial Registration clinicaltrials.gov Identifier: NCT00056225

Oat: unique among the cereals

Abstract: This review is intended to focus on the composition of oat and its therapeutic potential in the pharmacology that supports its use to cure various maladies. Oat (Avena sativa) is distinct among the cereals due to its multifunctional characteristics and nutritional profile. Recent advancement in food and nutrition has revealed the importance of its various components. It is a good source of dietary fiber especially β-glucan, minerals and other nutrients. Oat and oat by products have been proven to be helpful in the treatment of diabetes and cardiovascular disorders. Oat bran in particular, is good source of B complex vitamins, protein, fat, minerals besides heart healthy soluble fiber β-glucan. The β-glucan has outstanding functional properties and is of immense importance in human nutrition. Different physiological effects of β-glucan are related to its viscosity, attenuation of postprandial plasma glucose and insulin responses, high transport of bile acids towards lower parts of the intestinal tract and high excretion of bile acids thereby lowering of serum cholesterol levels. Moreover, it is helpful against coeliac disease. The incorporation of oat grains and oat bran in the food products improves not only the nutrition but also a therapy against various maladies.

Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial.

Abstract: Context Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B(12) can lower plasma total homocysteine levels. Objective To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis. Design, setting, and participants Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes. Interventions Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780). Main outcome measures The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke. Results Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28). Conclusions This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease. Trial registration clinicaltrials.gov Identifier: NCT00354081.

Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms

Abstract: Severe vitamin B12 deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelination of nerves; alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio; imbalance of neurotrophic and neurotoxic cytokines; and/or accumulation of lactate in brain cells. This review summarizes the current knowledge concerning infantile vitamin B12 deficiency, including a pooled analysis of case studies of infants born to mothers with untreated pernicious anemia or a strict vegetarian lifestyle and a discussion of the mechanisms that may underlie the manifestations of deficiency.

The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide

Abstract: Aims/hypothesis This study is an analysis of the relationship between ultraviolet B (UVB) irradiance, the primary source of circulating vitamin D in humans, and age-standardised incidence rates of type 1 diabetes mellitus in children, according to region of the world.

How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis.

Abstract: Recently higher rates of autism diagnosis suggest involvement of environmental factors in causing this developmental disorder, in concert with genetic risk factors. Autistic children exhibit evidence of oxidative stress and impaired methylation, which may reflect effects of toxic exposure on sulfur metabolism. We review the metabolic relationship between oxidative stress and methylation, with particular emphasis on adaptive responses that limit activity of cobalamin and folate-dependent methionine synthase. Methionine synthase activity is required for dopamine-stimulated phospholipid methylation, a unique membrane-delimited signaling process mediated by the D4 dopamine receptor that promotes neuronal synchronization and attention, and synchrony is impaired in autism. Genetic polymorphisms adversely affecting sulfur metabolism, methylation, detoxification, dopamine signaling and the formation of neuronal networks occur more frequently in autistic subjects. On the basis of these observations, a "redox/methylation hypothesis of autism" is described, in which oxidative stress, initiated by environment factors in genetically vulnerable individuals, leads to impaired methylation and neurological deficits secondary to reductions in the capacity for synchronizing neural networks.

Nutrition in clinical practice—the refeeding syndrome: illustrative cases and guidelines for prevention and treatment

Abstract: The refeeding syndrome is a potentially lethal complication of refeeding in patients who are severely malnourished from whatever cause. Too rapid refeeding, particularly with carbohydrate may precipitate a number of metabolic and pathophysiological complications, which may adversely affect the cardiac, respiratory, haematological, hepatic and neuromuscular systems leading to clinical complications and even death. We aimed to review the development of the refeeding syndrome in a variety of situations and, from this and the literature, devise guidelines to prevent and treat the condition. We report seven cases illustrating different aspects of the refeeding syndrome and the measures used to treat it. The specific complications encountered, their physiological mechanisms, identification of patients at risk, and prevention and treatment are discussed. Each case developed one or more of the features of the refeeding syndrome including deficiencies and low plasma levels of potassium, phosphate, magnesium and thiamine combined with salt and water retention. These responded to specific interventions. In most cases, these abnormalities could have been anticipated and prevented. The main features of the refeeding syndrome are described with a protocol to anticipate, prevent and treat the condition in adults.

Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials.

Abstract: Plasma total homocysteine (Hcy) has been associated with cardiovascular risk in multiple large-scale epidemiological studies, and it has been considered as an independent risk factor for atherosclerosis. Homocysteine lowering, achieved after the introduction of the folate food fortification programme in North America, was accompanied by an accelerated decline of cardiovascular risk and especially of stroke. Although the initial clinical trials suggested that homocysteine-lowering treatment with folates and B vitamins induces coronary plaque regression, this finding was not confirmed by more recent clinical studies. Under the light of the findings from the recent large randomized clinical trials that failed to document a benefit of Hcy lowering on clinical outcome of patients with atherosclerosis, the role of Hcy as a risk factor and the efficacy of Hcy lowering against atherosclerosis have been questioned. Therefore, better understanding of the mechanisms relating Hcy and Hcy-lowering treatment with vascular function and atherogenesis is crucial, to help us understand why clinical trials failed to show a benefit from Hcy-lowering treatment. Are these therapeutic strategies ineffective because they fail to reduce intracellular Hcy levels and vascular redox state or should Hcy stop being considered as an independent risk factor for atherosclerosis from now on? In this review article, we provide a global approach of the molecular mechanisms relating Hcy with cardiovascular risk and introduce possible mechanistic explanations regarding the inability of clinical trials to detect any clinical benefit from Hcy-lowering treatment in secondary prevention. Finally, we provide clinical recommendations regarding the therapeutic strategies targeting homocysteine in the general population.

Coenzyme A biosynthesis: an antimicrobial drug target.

Abstract: Pantothenic acid, a precursor of coenzyme A (CoA), is essential for the growth of pathogenic microorganisms. Since the structure of pantothenic acid was determined, many analogues of this essential metabolite have been prepared. Several have been demonstrated to exert an antimicrobial effect against a range of microorganisms by inhibiting the utilization of pantothenic acid, validating pantothenic acid utilization as a potential novel antimicrobial drug target. This review commences with an overview of the mechanisms by which various microorganisms acquire the pantothenic acid they require for growth, and the universal CoA biosynthesis pathway by which pantothenic acid is converted into CoA. A detailed survey of studies that have investigated the inhibitory activity of analogues of pantothenic acid and other precursors of CoA follows. The potential of inhibitors of both pantothenic acid utilization and biosynthesis as novel antibacterial, antifungal and antimalarial agents is discussed, focusing on inhibitors and substrates of pantothenate kinase, the enzyme catalysing the rate-limiting step of CoA biosynthesis in many organisms. The best strategies are considered for identifying inhibitors of pantothenic acid utilization and biosynthesis that are potent and selective inhibitors of microbial growth and that may be suitable for use as chemotherapeutic agents in humans.

Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case–control study

Abstract: Summary Background DNA hypomethylation has been suggested to cause genomic instability and increase cancer risk. We aimed to test the hypothesis that DNA hypomethylation is associated with increased risk of bladder cancer. Methods We measured cytosine methylation (5-mC) content in genomic DNA from blood cells from patients with bladder cancer enrolled in a large case–control study in Spain between Jan 1, 1998, and Dec 31, 2001. Cases were men and women with newly diagnosed and histologically confirmed urothelial carcinoma of the bladder. Controls were selected from patients admitted to the same hospital for diseases or conditions unrelated to smoking or other known risk factors for bladder cancer. Controls were individually matched to cases on age (within 5 years), sex, race, and area of hospital referral. 5-mC content was measured in leucocyte DNA by use of a combination of high-performance capillary electrophoresis, Hpa II digestion, and densitometry. Data on demographics, 34 polymorphisms in nine folate metabolism genes, and nutritional intake of six B vitamins (including folate), alcohol, and smoking were assessed as potential confounders. Relative 5-mC content was expressed as a percentage (%5-mC) with respect to the total cytosine content (the sum of methylated and non-methylated cytosines). The primary endpoint was median %5-mC DNA content. Findings %5-mC was measured in leucocyte DNA from 775 cases and 397 controls. Median %5-mC DNA was significantly lower in cases (3·03% [IQR 2·17–3·56]) than in controls (3·19% [2·46–3·68], p=0·0002). All participants were subsequently categorised into quartiles by %5-mC content in controls. When the highest quartile of %5-mC content was used as the reference category (Q4), the following adjusted odds ratios (OR) and 95% CI were recorded for decreasing methylation quartiles: OR (Q3) 2·05 (95% CI 1·37–3·06); OR (Q2) 1·62 (1·07–2·44); and OR (Q1) 2·67 (1·77–4·03), p for trend Interpretation For the first time, to our knowledge, we have shown in a large case–control study that leucocyte DNA hypomethylation is associated with increased risk of developing bladder cancer, and this association is independent of smoking and the other assessed risk factors. Amount of global methylation in genomic DNA could provide a useful biomarker of susceptibility to certain cancer types and further research is warranted. Funding Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA, and Fondo de Investigacion Sanitaria, Spain (G03/174).

The Worldwide Challenge of the Dementias: A Role for B Vitamins and Homocysteine?

Abstract: Dementia has reached epidemic proportions, with an estimated 4.6 million new cases worldwide each year. With an aging world population, the prevalence of dementia will increase dramatically in the next few decades. Of the predicted 114 million who will have dementia in 2050, about three-quarters will live in less developed regions. Although strongly age-related, dementia is not an inevitable part of aging but is a true disease, caused by exposure to several genetic and nongenetic risk factors. Prevention will be possible when the nongenetic risk factors have been identified. Apart from age, more than 20 nongenetic risk factors have been postulated, but very few have been established by randomized intervention studies. Elevated blood concentrations of total homocysteine and low-normal concentrations of B vitamins (folate, vitamin B12, and vitamin B6) are candidate risk factors for both Alzheimer's disease and vascular dementia. Seventy-seven cross-sectional studies on more than 34,000 subjects and 33 prospective studies on more than 12,000 subjects have shown associations between cognitive deficit or dementia and homocysteine and/or B vitamins. Biologically plausible mechanisms have been proposed to account for these associations, including atrophy of the cerebral cortex, but a definite causal pathway has yet to be shown. Raised plasma total homocysteine is a strong prognostic marker of future cognitive decline, and is common in world populations. Low-normal concentrations of the B vitamins, the main determinant of homocysteine concentrations, are also common and occur in particularly vulnerable sections of the population, such as infants and elderly. Large-scale randomized trials of homocysteine-lowering vitamins are needed to see if a proportion of dementia in the world can be prevented.

Vitamin B12 status and rate of brain volume loss in community-dwelling elderly

Abstract: Objectives: To investigate the relationship between markers of vitamin B 12 status and brain volume loss per year over a 5-year period in an elderly population. Methods: A prospective study of 107 community-dwelling volunteers aged 61 to 87 years without cognitive impairment at enrollment. Volunteers were assessed yearly by clinical examination, MRI scans, and cognitive tests. Blood was collected at baseline for measurement of plasma vitamin B 12 , transcobalamin (TC), holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), and serum folate. Results: The decrease in brain volume was greater among those with lower vitamin B 12 and holoTC levels and higher plasma tHcy and MMA levels at baseline. Linear regression analysis showed that associations with vitamin B 12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, ApoE e4 status, tHcy, and folate. Using the upper (for the vitamins) or lower tertile (for the metabolites) as reference in logistic regression analysis and adjusting for the above covariates, vitamin B 12 in the bottom tertile ( Conclusion: Low vitamin B 12 status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly.

Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial.

Abstract: Context Folate, vitamin B 6 , and vitamin B 12 are thought to play an important role in cancer prevention Objective To evaluate the effect of combined folic acid, vitamin B 6 , and vitamin B 12 treatment on cancer risk in women at high risk for cardiovascular disease Design, Setting, and Participants In the Women's Antioxidant and Folic Acid Cardiovascular Study, 5442 US female health professionals aged 42 years or older, with preexisting cardiovascular disease or 3 or more coronary risk factors, were randomly assigned to receive either a daily combination of folic acid, vitamin B 6 , and vitamin B 12 or a matching placebo They were treated for 73 years from April 1998 through July 31, 2005 Intervention Daily supplementation of a combination of 25 mg of folic acid, 50 mg of vitamin B 6 , and 1 mg of vitamin B 12 (n = 2721) or placebo (n = 2721) Main Outcome Measures Confirmed newly diagnosed total invasive cancer or breast cancer Results A total of 379 women developed invasive cancer (187 in the active treatment group and 192 in the placebo group) Compared with placebo, women receiving the active treatment had similar risk of developing total invasive cancer (1011/10 000 person-years for the active treatment group vs 1043/10 000 person-years for placebo group; hazard ratio [HR], 097; 95% confidence interval [CI], 079-118; P = 75), breast cancer (378/10 000 person-years vs 456/10 000 person-years, respectively; HR, 083; 95% CI, 060-114; P = 24), or any cancer death (246/10 000 person-years vs 301/10 000 person-years, respectively; HR, 082; 95% CI, 056-121; P = 32) Conclusion Combined folic acid, vitamin B 6 , and vitamin B 12 treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era Trial Registration clinicaltrialsgov Identifier: NCT00000541

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

Abstract: In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease, and Alzheimer's disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic, or vascular processes. We report here that feeding male C57BL6/J mice a B-vitamin-deficient diet for 10 weeks induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies (r = -0.757, P < 0.001), and with plasma total homocysteine (r = -0.631, P = 0.007). Feeding mice a methionine-rich diet produced similar but less pronounced effects. Our findings suggest that cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration. Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.

Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression.

Abstract: Background The role of folate, vitamin B12 and homocysteine levels in depression is not clear. Aims To investigate cross-sectional and prospective associations between folate, B12 and homocysteine levels and late-life depression. Method A total of 732 Korean people aged 65 years or over were evaluated at baseline. Of the 631 persons who were not depressed, 521 (83%) were followed over a period of 2–3 years and incident depression was ascertained with the Geriatric Mental State schedule. Serum folate, serum vitamin B12 and plasma homocysteine levels were assayed at both baseline and follow-up. Results Lower levels of folate and vitamin B12 and higher homocysteine levels at baseline were associated with a higher risk of incident depression at follow-up. Incident depression was associated with a decline in vitamin B12 and an increase in homocysteine levels over the follow-up period. Conclusions Lower folate, lower vitamin B12 and raised homocysteine levels may be risk factors for late-life depression.

Common variants of FUT2 are associated with plasma vitamin B12 levels

Abstract: David Hunter and colleagues report the discovery of associations between variants in FUT2 and plasma vitamin B12 levels. FUT2 encodes α,1,2-fucosyltransferase and is the classic human secretor locus that determines the secretion status of ABO blood group antigens. We identified a strong association (P = 5.36 × 10−17) between rs492602 in FUT2 and plasma vitamin B12 levels in a genome-wide scan (n = 1,658) and an independent replication sample (n = 1,059) from the Nurses' Health Study. Women homozygous for the rs492602[G] allele had higher B12 levels. This allele is in strong linkage disequilibrium with the FUT2 nonsecretor variant encoding W143X, suggesting a plausible mechanism for altered B12 absorption and plasma levels.

Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention.

Abstract: Alzheimer’s disease (AD) is the most common form of dementia. AD initially targets memory and progressively destroys the mind. The brain atrophies as the neocortex suffers neuronal, synaptic, and dendritic losses, and the “hallmark” amyloid plaques and neurofibrillary tangles proliferate. Pharmacological management, at best, is palliative and transiently effective, with marked adverse effects. Certain nutrients intrinsic to human biochemistry (orthomolecules) match or exceed pharmacological drug benefits in double-blind, randomized, controlled trials (RCT), with superior safety. Early intervention is feasible because its heritability is typically minimal and pathological deterioration is detectable years prior to diagnosis. The syndrome amnestic mild cognitive impairment (aMCI) exhibits AD pathology and to date has frustrated attempts at intervention. The condition ageassociated memory impairment (AAMI) is a nonpathological extreme of normal brain aging, but with less severe cognitive impairment than aMCI. AAMI is a feasible target for early intervention against AD, beginning with the modifiable AD risk factors – smoking, hypertension, homocysteine, type 2 diabetes, insulin resistance, and obesity. Stress reduction, avoidance of toxins, and mental and physical exercise are important aspects of prevention. The diet should emphasize omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA); flavonoids and other antioxidant nutrients; and B vitamins, especially folate, B 6 , and B 12 . Dietary supplementation is best focused on those proven from RCT: the phospholipids phosphatidylserine (PS) and glycerophosphocholine (GPC), the energy nutrient acetyl-L-carnitine, vitamins C and E, and other antioxidants. A comprehensive integrative strategy initiated early in cognitive decline is the most pragmatic approach to controlling progression to Alzheimer’s disease. (Altern Med Rev 2008;13(2):85-115)

Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.

Abstract: Aim Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. Methods Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). Results After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. Conclusion Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.

Homocysteine, B-vitamins and CVD.

Abstract: There is considerable interest in plasma homocysteine (tHcy) as a CVD risk factor. Although the secondary prevention trials published to date have been inconclusive in confirming a benefit of tHcy-lowering treatment with B-vitamins on CVD events generally, such studies are widely recognised to have been insufficiently powered to detect a significant effect for the predicted magnitude of association between tHcy and heart disease risk, and therefore cannot be interpreted as evidence that no relationship exists. In fact, a recent meta-analysis of clinical trials has confirmed that folic acid supplementation reduces the risk of stroke, particularly in individuals without a history of stroke. Evidence supporting a causal relationship between elevated tHcy and heart disease also comes from genetic studies. The most important genetic determinant of tHcy in the general population is the common C677T variant in methylenetetrahydrofolate reductase (MTHFR) that results in higher tHcy. Individuals with the homozygous mutant (TT) genotype have a significantly higher (14-21%) risk of heart disease. Plasma tHcy is very responsive to intervention with the B-vitamins required for its metabolism, in particular folic acid, and to a lesser extent vitamins B12 and B6. Thus, although primarily aimed at reducing neural-tube defects, folic acid fortification may have an important role in the primary prevention of CVD via tHcy lowering. Besides folate, riboflavin is required as a cofactor for MTHFR and enhanced riboflavin status results in a marked lowering in tHcy specifically in individuals with the TT genotype, presumably by neutralising the variant form of the enzyme. About 10% of the UK and Irish populations have the TT genotype. In the present paper the potential role of folate and related B-vitamins in the primary prevention of CVD and the implications for nutrition policy are explored.