B-group Vitamins Research Articles

Stroke: roles of B vitamins, homocysteine and antioxidants

In the present review concerning stroke, we evaluate the roles of B vitamins, homocysteine and antioxidant vitamins. Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. Several studies have reported important benefits on reducing the risk of stroke and improving the post-stroke-associated functional declines in patients who ate foods rich in micronutrients, including B vitamins and antioxidant vitamins E and C. Folic acid, vitamin B6 and vitamin B12 are all cofactors in homocysteine metabolism. Growing interest has been paid to hyperhomocysteinaemia as a risk factor for CVD. Hyperhomocysteinaemia has been linked to inadequate intake of vitamins, particularly to B-group vitamins and therefore may be amenable to nutritional intervention. Hence, poor dietary intake of folate, vitamin B6 and vitamin B12 are associated with increased risk of stroke. Elevated consumption of fruits and vegetables appears to protect against stroke. Antioxidant nutrients have important roles in cell function and have been implicated in processes associated with ageing, including vascular, inflammatory and neurological damage. Plasma vitamin E and C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke. After reviewing the observational and intervention studies, there is an incomplete understanding of mechanisms and some conflicting findings; therefore the available evidence is insufficient to recommend the routine use of B vitamins, vitamin E and vitamin C for the prevention of stroke. A better understanding of mechanisms, along with well-designed controlled clinical trials will allow further progress in this area.

Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women

The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the 'Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale' (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline.

Effects of Excess Nicotinic Acid on Growth and the Urinary Excretion of B-Group Vitamins and the Metabolism of Tryptophan in Weaning Rats

To determine the tolerable upper intake level of nicotinic acid in humans, we investigated the effects of excess nicotinic acid administration on body weight gain, food intake, and urinary excretion of water-soluble vitamins and the metabolism of tryptophan in weaning rats. The weaning rats were freely fed a niacin-free 20% casein diet (control diet) or the same diet with 0.1%, 0.3% or 0.5% nicotinic acid for 23 days. The excess nicotinic acid intake did not affect body weight gain, food intake, serotonin contents in the brain, stomach and small intestine, or the urinary excretions of water-soluble vitamins. Although excess nicotinic acid did not affect the upper part of the tryptophan-nicotinamide pathway, 0.5% nicotinic acid diet increased the urinary excretion of quinolinic acid. The diet containing more than 0.3% nicotinic acid also increased the urinary excretion of nicotinic acid, which is usually below the limit of detection. As determined from the results of body weight gain and food intake as indices for apparent adverse effects, the no-observed-adverse-effect-level (NOAEL) for nicotinic acid was 0.5% in diet, corresponding to 450 mg/kg body weight/day. As judged from in increase of urinary quinolinic acid and nicotinic acid as indices of metabolic change, NOAEL was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and the lowest-observed-adverse-effect-level (LOAEL) was 0.3% in diet, corresponding to 270 mg/kg body weight/day.

Effects of Excess Vitamin B1 or Vitamin B2 on Growth and Urinary Excretion of Water-soluble Vitamins in Weaning Rats

To determine the tolerable upper intake levels of vitamin B(1) and vitamin B(2) in humans, we investigated the effects of excess thiamin or riboflavin administration on body weight gain, food intake, tissue weights, and urinary excretion of B-group vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0006% thiamin-HCl or the same diet with 0.006%, 0.03%, 0.18% or 1.0% thiamin-HCl for 30 days, or the diet containing 0.0006% riboflavin or the same diet with 0.1%, 0.5 or 1.0% riboflavin for 22 days. Mild diarrhea was seen only in the rats fed with 1.0% thiamin-HCl diet. Excess thiamin-HCl or riboflavin did not affect body weight gains, food intake or tissue weights. The urinary excretions of water-soluble vitamins also did not differ among the diets. These results clearly showed that feeding a diet containing up to 1.0% thiamin-HCl or 1.0% riboflavin did not induce apparent adverse effects, and the no-observed-adverse-effect-levels (NOAELs) for thiamin-HCl and riboflavin in rats might be 1.0% in diet, corresponding to 900 mg/kg body weight/day.

Should Folate Supplements be Integrated with Workplace Nutrition Programs?

Suboptimal nutrition is known to underpin various occupational health issues. According to the International Labour Organization (ILO), poor diet at work may be costing countries up to 20% in lost productivity, either due to malnutrition in underdeveloped regions, or the over-nutrition and obesity epidemic that is currently occurring in many industrialised nations 1) . Obese workers, for example, are up to twice as likely to miss work when compared to their non-obese counterparts, while iron deficiency may lead to workplace accidents and has also been shown to reduce productivity by up to 30% 2) . Workplace nutrition programs and health promotion campaigns, therefore, offer an ideal opportunity for dietary interventions to help improve the health of employees on a long-term basis. Aside from maintaining adequate energy levels at work, nutritional interventions may also help address vitamin deficiencies which might otherwise have adverse sequelae for the offspring of female employees. Such programs would be considerably beneficial in workplaces that consist predominately of females at reproductive age. Folic Acid is the generic term for a large family of Bgroup vitamins occurring naturally in liver, fruit juice, certain leafy vegetables, cereals and grains 3) . These are largely in the form of methyl- and formyl-folate polyglutamates. The vitamin is essential for the production and maintenance of new cells, and by the early 1960s, it had been suggested that folic acid metabolism might be related to neural tube defects 4) . By the late 1980s evidence had mounted, with folic acid supplementation in the form of synthetic pteroylmonoglutamic acid being shown to reduce the prevalence of neural tube defects in some studies from the United States (US) 5) . In 1991, a groundbreaking and well-publicised investigation from the United Kingdom demonstrated that supplementation with synthetic folic acid may prevent over 70% of spina bifida and anencephaly cases 6) . Human folate status can be ascertained by blood measurements 7) , from which various population-based studies were able to demonstrate that its intake in the general community may be suboptimal. US national surveys conducted during the mid 1990s, for example, began to reveal that most adults were not consuming adequate amounts of this vitamin 8) . Given its role in the prevention of neural tube defects and the fact that many pregnancies are often unplanned, folic acid was subsequently introduced on a mandatory basis to grains, cere

Biosynthesis of lovastatin and (+)-geodin by Aspergillus terreus in batch and fed-batch culture in the stirred tank bioreactor

The simultaneous formation of mevinolinic acid (lovastatin; antihypercholesterolemia drug) and (+)-geodin (by-product) by Aspergillus terreus ATCC 20542 in the batch and fed-batch cultivation in the stirred tank bioreactor was investigated and described in this paper. The main factors influencing the formation of these two secondary metabolites were the initial nitrogen concentration and the aeration rate of the medium. The experiments aimed at achieving as high as possible lovastatin titre accompanied by as low as possible (+)-geodin concentration. The application of lactose-fed discontinuous fed-batch process allowed increasing lovastatin formation, in comparison with the batch process. Nevertheless (+)-geodin titre increased too. But the control of pH at the levels of 7.6 and 7.8 was successfully applied to repress the formation of the by-product both in batch and fed-batch experiments. Additionally, apart from pH control, the supplementation of the medium with nicotinamide and calcium pantothenate was used to facilitate the formation of lovastatin. The simultaneous pH control and B-group vitamin supplementation allowed achieving the best results in the batch cultivation.

Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat

Recent studies have demonstrated nicotinamide (NAM), a soluble B-group vitamin, to be an effective treatment in experimental models of traumatic brain injury (TBI). However, research on this compound has been limited to administration regimens starting shortly after injury. This study was conducted to establish the window of opportunity for NAM administration following controlled cortical impact (CCI) injury to the frontal cortex. Groups of rats were assigned to NAM (50 mg/kg), saline (1 ml/kg), or sham conditions and received contusion injuries or sham procedures. Injections of NAM or saline were administered at 15 min, 4 h, or 8 h post-injury, followed by five boosters at 24 h intervals. Following the last injection, blood was taken for serum NAM analysis. Animals were tested on a variety of tasks to assess somatosensory performance (bilateral tactile adhesive removal and vibrissae–forelimb placement) and cognitive performance (reference and working memory) in the Morris water maze. The results of the serum NAM analysis showed that NAM levels were significantly elevated in treated animals. Behavioral analysis on the tactile removal test showed that all NAM-treated groups facilitated recovery of function compared with saline treatment. On the vibrissae–forelimb placing test all NAM-treated groups also were significantly different from the saline-treated group. However, the acquisition of reference memory was only significantly improved in the 15-min and 4-h groups. In the working memory task both the 15-min and 4-h groups also improved working memory compared with saline treatment. The window of opportunity for NAM treatment is task-dependent and extends to 8 h for the sensorimotor tests but only extends to 4 h post-injury in the cognitive tests. These results suggest that a 50 mg/kg treatment regimen starting at the clinically relevant time point of 4 h may result in attenuated injury severity in the human TBI population.

Total plasma homocysteine correlates in women with gestational diabetes

We aim to assess serum total homocysteine (tHcy) associations with metabolic syndrome components and B-vitamins in women with gestational diabetes mellitus (GDM). We studied 61 consecutive pregnant women, 44 with GDM and 17 with normal glucose tolerance (CG). Serum homocysteine levels were analyzed by ELISA, using Bio-Rad reagents. Serum folates and vitamin B(12) concentrations were determined by chemiluminescent immunoassay, free fatty acids (FFA) and lipids enzymatically. Serum homocysteine levels were similar in both the GDM and the CG groups (8+/-2.0 vs 7.4+/-1.1 micromol/l, respectively). Women with GDM in comparison to CG women were characterized by higher values of homeostasis model of insulin resistance (HOMA-IR) (2.8+/-1.7 vs 1.6+/-0.9, P<0.01), serum triglycerides (2.7+/-0.9 vs 1.9+/-0.5 mmol/l, P<0.01) and FFA (0.6+/-0.2 vs 0.46+/-0.2 mmol/l, P<0.05). In GDM women serum tHcy correlated with vitamin B(12) (r= -0.47, P<0.01) and folates (r= -0.51, P<0.001); in CG women with HOMA-IR, a marker of insulin resistance (r= -0.49, P<0.05). In multiple regression analysis with serum tHcy as a dependent variable, folate and vitamin B(12) entered the analysis in GDM women (beta= -0.42 and -0.34, respectively, P<0.05), whereas in CG cystatin C and HOMA-IR entered the analysis (P<0.05). In women with GDM, serum homocysteine is significantly associated with vitamin B(12) and folate levels, while in healthy pregnant women with HOMA-IR and with kidney function. The results suggest the importance of the B-group vitamins in regulation of serum tHcy levels in women with insulin resistance/gestational diabetes, what might be relevant in protection against pregnancy complications associated with elevated tHcy in GDM women.

Age-Related Alterations of B-Group Vitamin Contents in Urine, Blood and Liver from Rats

To investigate how aging alters B-group vitamin metabolism, rats were fed with niacin-free 20% casein diet from 3 to 80 wk old, and the urinary excretions of the B group vitamins were periodically measured. The blood and liver B-group vitamin levels in 80-wk-old rats were also compared with those in 8-wk-old rats. The urinary excretion of thiamin, riboflavin, vitamin B6 metabolite 4-pyridoxic acid, pantothenic acid, folic acid and biotin were not altered during 540 d. The urinary vitamin B12 increased by 8-fold at 29 wk old, and further increased at 80 wk old. Conversion of nicotinamide from tryptophan gradually decreased to 60% from 29 to 48 wk old. Plasma PLP, vitamin B12 and folate levels in 80-wk-old rats were lower than those in 8-wk-old rats, consistent with lower liver vitamin B6 and folate levels in aged rats. Plasma and liver biotin levels in aged rats were higher than those in young rats. Other B-group vitamins such as vitamin B1, vitamin B2, niacin and pantothenic acid levels in blood and liver from aged rats were same as those from young rats. Alteration of vitamin B6 metabolism in particular is similar to the observations in elderly humans reported previously. Our findings suggest that aged rats can be useful models to investigate aging-related B-group vitamin metabolism.

Effects of Excess Folic Acid on Growth and Metabolism of Water-soluble Vitamins in Weaning Rats

In order to determine the tolerable upper intake level of folic acid in humans, we investigated the effects of excessive folic acid administration on the body weight gain, food intake, tissue weight, and metabolism of B-group vitamins in weaning rats. The rats were freely fed ordinary diet containing 0.0002% folic acid (control diet) or the same diet with 0.01%, 0.1%, or 1.0% folic acid for 29 days. The body weight gains and food intakes did not differ among the four groups. Diarrhea was not seen even in the 1.0% group. Excess folic acid did not affect the tissue weights of the brain, heart, liver, kidney, spleen, lung, or testis, or urinary excretion of other B-group vitamins. These results clearly showed that feeding a diet containing up to 1.0% folic acid did not affect the food intake, body weight gain, tissue weight, or urinary excretion of B-group vitamins in weaning rats.

Simultaneous determination of B-Group vitamins in enriched cookies

The objective of this research was to determine the levels of enrichment of vitamins B1, B2, B6 and B3 in different types and brands of enriched cookies. The chromatographic separation was performed in a C18 column with gradient elution and UV detection at 254 and 287 nm. The results show that only 5 of the 24 brands evaluated are in accordance with the Brazilian legislation with respect to the vitamin content declared on the labels. However, consumption of approximately 100-150 g of most of the brands supplies the recommended dietary intake for children and adults of the vitamins evaluated.

Relationship between Bioactive Minerals and Bioavailability of B-group vitamins

Relationship between Bioactive Minerals and Bioavailability of B-group vitamins

Low vitamin B6 and folic acid levels are associated with retinal vein occlusion independently of homocysteine levels

Retinal vein occlusion (RVO) is one of the most common retinal vascular disorders. During the last years, high levels of homocysteine (Hcy) have been demonstrated to be an independent risk factor for RVO. Aim of this study was to investigate the association among circulating B-group vitamins, Hcy and RVO. Thus, we studied 262 RVO patients and 262 age- and sex-comparable healthy subjects. Serum vitamin B6 was measured by HPLC, serum folic acid and vitamin B12 by radioimmunoassay and plasma Hcy by FPIA. Blood levels of vitamin B6, folate and Hcy, but not of vitamin B12, were found to be significantly different in patients as compared to healthy subjects. At the univariate analysis, the lowest tertile of vitamin B6 [odds ratio (OR) 4.03; 95% confidence interval (CI) 2.58–6.31; P < 0.0001)] and folate (OR 6.13; 95% CI 3.85–9.76, P < 0.0001), and the highest tertile of Hcy (OR 8.08; 95% CI 5.05–12.92, P < 0.0001) were found to be significantly associated with RVO. Moreover, at multivariate analysis, after adjustment for traditional cardiovascular risk factors, Hcy, and circulating levels of vitamins, respectively, the lowest tertile of vitamin B6 (OR 3.29; 95% CI 1.89–5.70, P < 0.0001) and folate (OR 5.41; 95% CI 3.08–9.51, P < 0.0001) and the highest tertile of Hcy (OR 2.58; 95% CI 1.12–5.94, P < 0.0001) maintained their significant association with RVO. In conclusion, the present study documents, on a large sample of patients, that low vitamin B6 levels, low folic acid levels and elevated Hcy levels are each independently associated with RVO.

Biosynthesis of food constituents: Vitamins. 2. Water-soluble vitamins: Part 2 - a review

This review article gives a survey of the biosynthetic pathways that lead to water-soluble vitamins in microorganisms, plants and some animals. The biosynthetic pathways leading to some the B-group vitamins (biotin, folacin, cobalamins) and to vitamin C are described in detail using reaction schemes and mechanisms with enzymes involved and detailed explanations based on chemical principles and mechanisms.

Simultaneous Determination of B-Group Vitamins in Enriched Brazilian Dairy Products

In addition to serving as good natural sources of vitamin B 2 , milk and milk products are currently being enriched with the vitamins B 1 , B 2 , B 6 , and nicotinamide in Brazil. The objective of this research was to evaluate the levels of enrichment of these products according to their availability in supermarkets in the Campinas (SP, Brazil) region. The separation of the vitamins was carried out on a C 18 column with gradient elution with acetonitrile and aqueous phase. Detection of vitamins was effected in the ultraviolet region and quantification by an external standard. The levels of vitamin B 2 determined in powdered whole milk, skimmed milk powder, and one brand of flavored lactic beverage, were practically double those stated on the packages. The same occurred with vitamins B 6 and PP (nicotinic acid + nicotinamide), when determined in the same lactic beverage and with vitamin B 6 , determined in acidified milk. The high levels of vitamin B 2 , naturally present in whole milk, and the predominance of the free form, allowed for the determination of this vitamin in non-enriched milk.

Analytical procedures for water-soluble vitamins in foods and dietary supplements: a review

Water-soluble vitamins include the B-group vitamins and vitamin C. In order to correctly monitor water-soluble vitamin content in fortified foods for compliance monitoring as well as to establish accurate data banks, an accurate and precise analytical method is a prerequisite. For many years microbiological assays have been used for analysis of B vitamins. However they are no longer considered to be the gold standard in vitamins analysis as many studies have shown up their deficiencies. This review describes the current status of analytical methods, including microbiological assays and spectrophotometric, biosensor and chromatographic techniques. In particular it describes the current status of the official methods and highlights some new developments in chromatographic procedures and detection methods. An overview is made of multivitamin extractions and analyses for foods and supplements.

Biosynthesis of food constituents: Vitamins. 2. Water-soluble vitamins: Part 1 - a review

This review article gives a survey of the generally accepted biosynthetic pathways that lead to water-soluble vitamins in microorganisms, plants and some animals. The biosynthetic pathways leading to the B-group vitamins (thiamin, riboflavin, nicotinic acid and nicotinamide, pantothenic acid, vitamin B&lt;sub&gt;6&lt;/sub&gt;) are described in detail using the reaction schemes, sequences, and mechanisms with the enzymes involved and detailed explanations based on chemical principles and mechanisms. Keywords:

Riboflavin status in acute ischaemic stroke

There is experimental evidence that riboflavin (vitamin B2) supplementation reduces oxidative damage and cerebral oedema following acute stroke. To measure riboflavin levels in acute stroke before and after supplementation with this vitamin. Ninety-six acute ischaemic stroke patients had their riboflavin status measured at baseline and then randomly assigned to receive 5 mg of oral riboflavin and other B-group vitamins within 12 h of the stroke onset and then daily or no B-vitamins for 14 days. Non-fasting venous blood was obtained at baseline, days 7 and 14 post-randomization for measurement of riboflavin status using erythrocyte glutathione reductase activity coefficient (EGRAC). EGRAC is a measure of riboflavin tissue saturation. This assay has the advantage of being extremely stable and sensitive. EGRAC values are inversely proportional to riboflavin status, so that values greater than 1.3 indicate biochemical deficiency. Fifty-one per cent of patients studied were riboflavin deficient at baseline. Fourteen days of riboflavin supplementation significantly improved the measure of B2 status compared with the control group. Seven out of 37 patients in the supplement group (19%) were riboflavin deficient compared with 22 out of 39 patients (56%) in the control group at the end of the treatment period (P=0.035 for the differences in cumulative changes between groups over 2 weeks). A high proportion of acute stroke patients were biochemically deficient of riboflavin immediately post-infarct. Supplementation with 5 mg of riboflavin for 2 weeks significantly improved riboflavin status; however, the clinical significance of these findings is not yet known.

B-group vitamins, MTHFR C677T polymorphism and carotid intima-media thickness in clinically healthy subjects

Plasma B-group vitamins and age may affect the carotid intima-media thickness (IMT) in subjects with different 677TT genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. A hospital-based cross-study. Genomic and Vascular Center, Changhua Christian Hospital, Changhua, Taiwan. Five hundred and forty-one clinically healthy subjects. Fasting plasma, homocysteine (Hcy), vitamin B(6), vitamin B(12), folate and B-mode carotid ultrasound. MTHFR genotype, plasma concentrations of folate, vitamin B(6) and vitamin B(12) and age were significantly correlated to the plasma Hcy concentration. MTHFR 677TT carriers had higher concentrations of Hcy than did subjects with the CC and CT genotypes. Age, sex, body mass index and plasma Hcy were independent contributors to increase carotid IMT. However, with stratification by mean value of age and B-group vitamins concentrations, we found that at advanced age, lower plasma folate and vitamin B(12) were three risk factors involved in the enhancing effect of the MTHFR 677TT genotype on the increase of plasma Hcy and carotid IMT. MTHFR 677TT-related carotid atherosclerosis was only identified in healthy elderly subjects with lower level of plasma folate and vitamin B(12). Changhua Christian Hospital.

Hyperhomocysteinemia and Mortality after Coronary Artery Bypass Grafting

BackgroundThe independent prognostic impact, as well as the possible causal role, of hyperhomocysteinemia (HHcy) in coronary artery disease (CAD) is controversial. No previous study specifically has addressed the relationship between HHcy and mortality after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the prognostic impact of HHcy after CABG surgery.Methodology and Principal FindingsWe prospectively followed 350 patients who underwent elective CABG between May 1996 and May 1999. At baseline, fasting total homocysteine (tHcy) levels were measured in all participants, and a post-methionine loading (PML) test was performed in 77.7% of them (n = 272). After a median follow-up of 58 months, 33 patients (9.4%) had died, 25 because of cardiovascular events. HHcy, defined by levels higher than the 90th percentile (25.2 µmol/L) of the population's distribution, was significantly associated to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002 [log-rank test 9.76], respectively). The PML test had no prognostic value. After multiple adjustment for other univariate predictors by Cox regression, including statin therapy (the most powerful predictor in uni-/multivariate analyses), high-sensitivity C Reactive Protein (hs-CRP) levels, and all known major genetic (MTHFR 677C→T polymorphism) and non-genetic (B-group vitamin status and renal function) tHcy determinants, HHcy remained an independent prognostic factor for mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001).ConclusionsHHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers.