Vitamin supplementation reduces the level of homocysteine in the urine of autistic children

Significant differences in homocysteine levels in the urine of autistic children are observed. We hypothesized that vitamin supplementation might reduce the level of urinary homocysteine. To rationalize such a hypothesis, analyses were performed using the gas chromatography/mass spectrometry method. The homocysteine level in the urine of autistic children was measured twice: (1) before vitamin supplementation (group C, 30 autistic children) and (2) after supplementation, with either folic acid and vitamins B₆ and B₁₂ (group A1, 24 autistic children) or vitamins B₆ and B₁₂ alone (group A2, 6 autistic children). The homocysteine level in the urine of autistic children before vitamin supplementation was 2.41 ± 1.10 mmol/mol creatinine (mean ± SD difference). After treatment, the homocysteine level was reduced to 1.13 ± 0.44 and 1.33 ± 0.39 mmol/mol creatinine for A1 and A2 groups, respectively. The intake of vitamins B₆ and B₁₂, together with folic acid, was found to be more effective in lowering the levels of urinary homocysteine than the intake of vitamins B₆ and B₁₂ alone. Our findings may lead to the recommendation of including vitamins B₆ and B₁₂ together with folic acid supplementation in the diets of children with autism.     

Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects

BACKGROUND: Betaine comes from the diet and from choline, and it is associated with vascular disease in some patient groups. Betaine supplementation lowers plasma total homocysteine. OBJECTIVE: We compared the acute effects of dietary and supplementary betaine and choline on plasma betaine and homocysteine under standard conditions and after a methionine load. DESIGN: In a randomized crossover study, 8 healthy men (19-40 y) consumed a betaine supplement (approximately 500 mg), high-betaine meal (approximately 517 mg), choline supplement (500 mg), high-choline meal (approximately 564 mg), high-betaine and -choline meal (approximately 517 mg betaine, approximately 622 mg choline), or a low-betaine and -choline control meal under standard conditions or postmethionine load. Plasma betaine, dimethylglycine, and homocysteine concentrations were measured hourly for 8 h and at 24 h after treatment. RESULTS: Dietary and supplementary betaine raised plasma betaine concentrations relative to control (P < 0.001) under standard conditions. This was not associated with raised plasma dimethylglycine concentration, and no significant betaine appeared in the urine. A small increase in dimethylglycine excretion was observed when either betaine or choline was supplied (P = 0.011 and < 0.001). Small decreases in plasma homocysteine 6 h after ingestion under standard conditions (P < or = 0.05) were detected after a high-betaine meal and after a high-betaine and high-choline meal. Dietary betaine and choline and betaine supplementation attenuated the increase in plasma homocysteine at both 4 and 6 h after a methionine load (P < or = 0.001). CONCLUSIONS: Dietary betaine and supplementary betaine acutely increase plasma betaine, and they and choline attenuate the postmethionine load rise in homocysteine concentrations.     

The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people

The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 microg cobalamin (vitamin B12), or 1000 microg cobalamin plus 400 microg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36%, and increased betaine concentrations by 38%. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0.07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.     

Type of Alcoholic Beverage and Risk of Head and Neck Cancer--A Pooled Analysis Within the INHANCE Consortium

The authors pooled data from 15 case-control studies of headand neck cancer (9,107 cases, 14,219 controls) to investigatethe independent associations with consumption of beer, wine,and liquor. In particular, they calculated associations withdifferent measures of beverage consumption separately for subjectswho drank beer only (858 cases, 986 controls), for liquor-onlydrinkers (499 cases, 527 controls), and for wine-only drinkers(1,021 cases, 2,460 controls), with alcohol never drinkers (1,124cases, 3,487 controls) used as a common reference group. Theauthors observed similar associations with ethanol-standardizedconsumption frequency for beer-only drinkers (odds ratios (ORs)= 1.6, 1.9, 2.2, and 5.4 for 5, 6–15, 16–30, and>30 drinks per week, respectively; P_trend < 0.0001) andliquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001).Among wine-only drinkers, the odds ratios for moderate levelsof consumption frequency approached the null, whereas thosefor higher consumption levels were comparable to those of drinkersof other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P <0.0001). Study findings suggest that the relative risks of headand neck cancer for beer and liquor are comparable. The authorsobserved weaker associations with moderate wine consumption,although they cannot rule out confounding from diet and otherlifestyle factors as an explanation for this finding. Giventhe presence of heterogeneity in study-specific results, theirfindings should be interpreted with caution. alcohol drinking; alcoholic beverages; beer; case-control studies; head and neck neoplasms; meta-analysis; wine     

Vitamin Status among Breastfed Infants in Bhaktapur,Nepal

Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B₆, B₁₂ and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5′-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B₆ deficiency and vitamin B₁₂ deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal.     

Relationship of dimethylglycine, choline, and betaine with oxoproline in plasma of pregnant women and their newborn infants

Choline and glycine are inter-related through their roles in methyl metabolism. Choline is metabolized to betaine, which donates a methyl group to homocysteine to form methionine, also generating dimethylglycine, which is further metabolized to glycine. Choline is transported across the placenta and is higher in fetal than maternal plasma. Placental glycine transfer, however, is limited and poor glycine status has been suggested in preterm infants. Insufficient glycine for glutathione (GSH) synthesis results in increased metabolism of gamma-glutamyl cysteine to 5-oxoproline. We measured plasma 5-oxoproline as a metabolic indicator to address whether choline, via dimethylglycine, contributes physiologically relevant amounts of glycine in pregnancy. Blood was collected from healthy term pregnant women and their newborn infants at delivery (n = 46) and nonpregnant healthy women (n = 19) as a reference group. Plasma choline, betaine, dimethylglycine, homocysteine, methionine, and 5-oxoproline were quantified by HPLC-tandem MS. Plasma choline was 45% higher, but betaine was 63% lower and dimethylglycine was 28% lower in pregnant than nonpregnant women (P < 0.01). Higher white blood cell choline dehydrogenase messenger RNA levels in a random subset of pregnant (n = 8) than nonpregnant women (n = 7) (P < 0.01) suggest increased betaine and dimethylglycine turnover rather than decreased synthesis. Plasma choline, betaine, and dimethylglycine were higher (P < 0.001) in fetal plasma (36.4 +/- 13, 29.4 +/- 1.0, and 2.44 +/- 0.12 micromol/L, respectively) than maternal plasma (15.3 +/- 0.42, 14.1 +/- 0.6 and 1.81 +/- 0.12 micromol/L, respectively). Concentrations of 5-oxoproline and dimethylglycine were inversely (P < 0.05) correlated in maternal (Spearman rho = -0.35) and fetal plasma (Spearman rho = -0.32), suggesting that choline, via dimethylglycine, contributes glycine for GSH synthesis in human development.     

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

Purpose  

Cardiovascular risk factors such as elevated levels of asymmetric dimethylarginine (ADMA)/C-reactive protein (CRP) and homocysteine are potentially related to essential micronutrients such as certain B vitamins and antioxidant vitamins. The aim of the present study was to investigate whether supplementation with moderate doses of B vitamins and/or antioxidants could alter either ADMA and/or CRP concentrations in middle-aged, apparently healthy men with mildly elevated homocysteine levels.     

Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis

Cystic fibrosis (CF) is associated with many clinical complications including steatosis for which the relation to defective CF transmembrane conductance regulator protein is unclear. Choline deficiency results in hepatic steatosis. Choline is the precursor of betaine, which donates methyl groups for remethylation of homocysteine to methionine and dimethylglycine. Previously, we have shown phospholipid malabsorption and increased plasma homocysteine in children with CF. In these studies we used normal phase HPLC with tandem mass spectrometry to determine plasma choline, betaine, and dimethylglycine in children with CF (n = 34) and healthy control children without CF (n = 15). Plasma choline, betaine, and dimethylglycine were significantly lower in children with CF (means +/- SEM, 6.48 +/- 0.35, 23.8 +/- 1.49, 1.49 +/- 0.13 mumol/L, respectively) than in children without CF (8.98 +/- 0.46, 37.3 +/- 1.84, 3.01 +/- 0.17 mumol/L, respectively). Plasma choline (r = 0.373, P = 0.007) and betaine (r = 0.399, P = 0.005) were positively related to methionine, and choline was inversely related to homocysteine (r = -0.316, P = 0.03). Choline, betaine, and dimethylglycine were all significantly and positively related to the plasma S-adenosylmethionine:S-adenosylhomocysteine (SAM:SAH) ratio (r = 0.294, r = 0.377, r = 0.442, respectively; P < 0.05). The plasma choline:betaine and betaine:dimethylglycine ratios did not differ between the children with CF and the control children, suggesting no increase in betaine synthesis, or betaine-dependent remethylation of homocysteine. These studies suggest that choline depletion may contribute to increased homocysteine in children with CF. Choline depletion and altered thiol metabolism may contribute to the clinical complications associated with CF.     

Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years

Summary Background Deficiency of folic acid, vitamin B₆ and/or vitamin B₁₂ can result in elevated total plasma homocysteine concentrations (tHcy), which are considered to be a risk factor for vascular disease. Studies have shown that supplementation of the three vitamins can lower tHcy even in subjects with tHcy in the normal range. Aim of the study The aim of this study was to evaluate the effect of a 6 month supplementation with vitamin B₆, B₁₂ and folate on the concentrations of total plasma homocysteine and serum methylmalonic acid (MMA) of elderly women. Methods The study was designed as a randomized placebo controlled doubleblind trial, and 220 healthy women (aged 60–91 years) were involved. The vitamin and mineral capsule contained pyridoxine (3.4 mg), folic acid (400 µg) and cobalamin (9 µg) in addition to other micronutrients. Blood concentrations of folate, cobalamin, tHcy, MMA and the activity coefficient of erythrocyte alpha-aspartic aminotransferase (alpha-EAST) were measured at baseline and after 6 months of supplementation. Dietary intake was evaluated at the beginning and the end of the intervention by two 3–day diet records. Results Median concentrations of serum cobalamin, serum folate and erythrocyte folate increased significantly and tHcy and alpha–EAST activity (indicative of improved status of vitamin B₆) coefficient decreased significantly in the supplemented group. Median MMA concentration of the supplemented group was significantly lower than that of the placebo group after the intervention. The vitamin supplementation had a greater decreasing effect on the tHcy concentration of volunteers with lower vitamin and higher tHcy initial concentrations. In a linear regression model, baseline tHcy, serum folate, age and alpha–EAST activity coefficient were significantly correlated with the change in tHcy. The change in MMA in the supplement group was significantly associated to the baseline MMA values. Conclusions Our results show that a 6 month supplementation including physiological dosages of B vitamins improves the status of these nutrients and reduces tHcy in presumed healthy elderly women.     

Folic acid and vitamin B12 supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized,double-blind,placebo-controlled trial

An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B₁₂. The aim of this study was to determine whether there is an impact of folic acid and vitamin B₁₂ supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B₁₂ will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 μmol/L. Participants were randomly assigned to receive either a daily folic acid (800 μg) and vitamin B₁₂ (1000 μg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 μmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B₁₂ as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.     

Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations

BACKGROUND: Remethylation of homocysteine to methionine can occur through either the folate-dependent methionine synthase pathway or the betaine-dependent betaine-homocysteine methyltransferase pathway. The relevance of betaine as a determinant of fasting total homocysteine (tHcy) is not known, nor is it known how the 2 remethylation pathways are interrelated. OBJECTIVE: The objectives of the study were to examine the relation between plasma betaine concentration and fasting plasma tHcy concentrations and to assess the effect of folic acid supplementation on betaine concentrations in healthy subjects. DESIGN: A double-blind randomized trial of 6 incremental daily doses of folic acid (50-800 microg/d) or placebo was carried out in 308 Dutch men and postmenopausal women (aged 50-75 y). Fasted blood concentrations of tHcy, betaine, choline, dimethylglycine, and folate were measured at baseline and after 12 wk of vitamin supplementation. RESULTS: Concentrations of tHcy were inversely related to the betaine concentration (r = -0.17, P < 0.01), and the association was independent of age, sex, and serum concentrations of folate, creatinine, and cobalamin. Folic acid supplementation increased betaine concentration in a dose-dependent manner (P for trend = 0.018); the maximum increase (15%) was obtained at daily doses of 400-800 microg/d. CONCLUSIONS: The plasma betaine concentration is a significant determinant of fasting tHcy concentrations in healthy humans. Folic acid supplementation increases the betaine concentration, which indicates that the 2 remethylation pathways are interrelated.     

Reduced plasma homocysteine in obese red wine consumers: a potential contributor to reduced cardiovascular risk status

BACKGROUND: Moderate alcohol consumption is associated with improved vascular risk profile and decreased mortality in the middle aged. An elevated homocysteine concentration is an independent risk factor for cardiovascular disease. OBJECTIVE: To examine the relationship between alcohol consumption and homocysteine concentrations in severely obese patients (body mass index (BMI)>35). DESIGN: A careful alcohol history was obtained from 350 (male:female 1:5) consecutive patients as part of preoperative assessment for surgical treatment of obesity. Data were obtained concerning amount, frequency, timing and type of alcohol consumption. Fasting homocysteine, serum folate and vitamin B(12) concentrations were measured. Differences between groups were assessed using Student t-test, and ANOVA. Linear regression was used to assess factors influencing homocysteine concentration. RESULTS: There is a U-shaped relationship between alcohol consumption and homocysteine concentrations, with light to moderate consumption being associated with lower concentrations. Those consuming <100 g/week (n=165) of alcohol had geometric mean (95% CI of mean) serum homocysteine concentrations of 8.5 (8.2-8.9) micromol/l compared with 9.5 (9.1-9.9) micromol/l for non or rare consumers (n=153; P=0.001). The lower concentrations of homocysteine in regular consumers were associated with higher folate concentrations of 9.4 (8.6-10.2) ng/ml when compared with non-consumers 7.5 (7.1-7.8) ng/ml (P=0.001). Red wine consumers (n=42) had lower fasting concentrations of homocysteine 7.8 (7.5-8.1) micromol/l compared with 153 non-consumers 9.4 (9.0-9.8) micromol/l (P<0.001), 82 beer and spirit consumers 9.0 (8.4-9.7) micromol/l (P=0.005) and 73 white wine consumers 8.8 (8.2-9.4 micromol/l (P=0.013). Red wine consumption was an independent predictor for lower homocysteine concentrations. CONCLUSION: Mild to moderate alcohol consumption, especially red wine consumption, in obese subjects is associated with lower fasting homocysteine concentrations. This may reduce cardiovascular risk and help explain the 'French paradox'.     

Effects of dietary supplementation of high-dose folic acid on biomarkers of methylating reaction in vitamin B12-deficient rats

Folate is generally considered as a safe water-soluble vitamin for supplementation. However, we do not have enough information to confirm the potential effects and safety of folate supplementation and the interaction with vitamin B₁₂ deficiency. It has been hypothesized that a greater methyl group supply could lead to compensation for vitamin B₁₂ deficiency. On this basis, the present study was conducted to examine the effects of high-dose folic acid (FA) supplementation on biomarkers involved in the methionine cycle in vitamin B₁₂-deficient rats. Sprague-Dawley rats were fed diets containing either 0 or 100 µg (daily dietary requirement) vitamin B₁₂/kg diet with either 2 mg (daily dietary requirement) or 100 mg FA/kg diet for six weeks. Vitamin B₁₂-deficiency resulted in increased plasma homocysteine (p<0.01), which was normalized by dietary supplementation of high-dose FA (p<0.01). However, FA supplementation and vitamin B₁₂ deficiency did not alter hepatic and brain S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations and hepatic DNA methylation. These results indicated that supplementation of high-dose FA improved homocysteinemia in vitamin B₁₂-deficiency but did not change SAM and SAH, the main biomarkers of methylating reaction.     

Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis

BACKGROUND/OBJECTIVESThis study was conducted to examine relationships between dietary habits and intakes of antioxidants and B vitamins and the risk of ischemic stroke, and to compare dietary factors according to the presence of cerebral artery atherosclerosis and stroke subtypes.SUBJECTS/METHODSA total of 147 patients and 144 control subjects were recruited consecutively in the metropolitan area of Seoul, Korea. Sixty participants each in the case and control groups were included in analyses after 1:1 frequency matching. In addition, 117 acute ischemic stroke patients were classified into subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines. Dietary intake was measured using a semi-quantitative food frequency questionnaire composed of 111 food items and plasma lipid and homocysteine levels were analyzed.RESULTSWhen compared with control subjects, stroke patients had unfavorable dietary behaviors and lower intakes of fruits (73.1 ± 83.2 g vs. 230.9 ± 202.1 g, P < 0.001), vegetables (221.1 ± 209.0 g vs. 561.7 ± 306.6 g, P < 0.001), and antioxidants, including vitamins C, E, B₆, β-carotene, and folate. The intakes of fruits, vegetables, vitamin C, and folate were inversely associated with the risk of ischemic stroke after adjusting for confounding factors. Intakes of vegetables, vitamins C, B₆, B₁₂, and folate per 1,000 kcal were lower in ischemic stroke with cerebral atherosclerosis than in those without. Overall vitamin B₁₂ intake per 1,000 kcal differed according to the TOAST classification (P = 0.004), but no differences among groups existed based on the post-hoc test.CONCLUSIONSWhen compared with control subjects, ischemic stroke patients, particularly those with cerebral atherosclerosis, had unfavorable dietary intake, which may have contributed to the development of ischemic stroke. These results indicate that proper dietary recommendations are important for the prevention of ischemic stroke.     

Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets

Choline is an important component of the human diet and is required for the endogenous synthesis of choline-containing phospholipids, acetylcholine and betaine. Choline can also be synthesised de novo by the sequential methylation of phosphatidylethanolamine to phosphatidylcholine. Vitamins B6, B12 and folate can enhance methylation capacity and therefore could influence choline availability not only by increasing endogenous choline synthesis but also by reducing choline utilisation. In the present experiment, we determined whether combined supplementation of these B vitamins affects plasma choline concentration in a rat model of mild B vitamin deficiency which shows moderate increases in plasma homocysteine. To this end, we measured plasma choline and homocysteine concentrations in rats that had consumed a B vitamin-poor diet for 4 weeks after which they were either continued on the B vitamin-poor diet or switched to a B vitamin-enriched diet for another 4 weeks. Both diets contained recommended amounts of choline. Rats receiving the B vitamin-enriched diet showed higher plasma choline and lower plasma homocysteine concentrations as compared to rats that were continued on the B vitamin-poor diet. These data underline the interdependence between dietary B vitamins and plasma choline concentration, possibly via the combined effects of the three B vitamins on methylation capacity.     

B Vitamins and the Brain: Mechanisms,Dose and Efficacy—A Review

The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B₉/B₁₂/B₆) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health.     

High prevalence of hyperhomocysteinemia in chronic alcoholism: the importance of the thermolabile form of the enzyme methylenetetrahydrofolate reductase (MTHFR)

Alcoholism is related to malnutrition and low levels of several vitamins that take part in the metabolism of homocysteine. The objective of the study was to analyze the prevalence of hyperhomocysteinemia in patients with heavy alcohol intake and the factors on which it depends. Included in the study were 103 hospitalized heavy drinkers (i.e., patients with an intake of alcohol greater than 80 g per day). Serum homocysteine, folate, and vitamin B₁₂ levels, plasma vitamin B₆ levels, and CT677 polymorphisms of methylenetetrahydrofolate reductase (MTHFR) were determined. We also recorded the intensity of alcoholism, the status of nutrition, and the existence of liver cirrhosis. Determination of biochemical data was repeated after 15 days of withdrawal. Serum homocysteine levels were found to be significantly elevated, whereas serum folate and plasma B₆ levels were significantly decreased. Serum homocysteine levels were significantly higher in those heavy drinkers who showed the TT polymorphism of MTHFR, with a prevalence of hyperhomocysteinemia of 84.2% in the homozygote TT, 54.3% in the heterozygote CT, and 31.6% in the normal CC genotype. Serum homocysteine inversely correlated with serum folate, serum B₁₂, and plasma B₆ levels. We did not find any relation between serum homocysteine and intensity of alcoholism, nutritional status, or liver cirrhosis. Serum folate levels were significantly decreased in heavy drinkers, mainly depending on irregular feeding and malnutrition. After 15 days of withdrawal, serum homocysteine levels significantly decreased, whereas folate, B₁₂, and B₆ levels significantly increased. The conclusion is that heavy drinkers show a high prevalence of hyperhomocysteinemia related to low levels of folate, B₆, and B₁₂ and to the TT polymorphism of MTHFR. © 2001 Elsevier Science Inc. All rights reserved.     

Lead Exposure,B Vitamins,and Plasma Homocysteine in Men 55 Years of Age and Older: The VA Normative Aging Study

Background: Lead (Pb) exposure may influence the plasma concentration of homocysteine, a one-carbon metabolite associated with cardiovascular and neurodegenerative diseases. Little is known about the associations between Pb and homocysteine over time, or the potential influence of dietary factors.Objectives: We examined the longitudinal association of recent and cumulative Pb exposure with homocysteine concentrations and the potential modifying effect of dietary nutrients involved in one-carbon metabolism.Methods: In a subcohort of the Veterans Affairs (VA) Normative Aging Study (1,056 men with 2,301 total observations between 1993 and 2011), we used mixed-effects models to estimate differences in repeated measures of total plasma homocysteine across concentrations of Pb in blood and tibia bone, assessing recent and cumulative Pb exposure, respectively. We also assessed effect modification by dietary intake and plasma concentrations of folate, vitamin B₆, and vitamin B₁₂.Results: An interquartile range (IQR) increment in blood Pb (3 μg/dL) was associated with a 6.3% higher homocysteine concentration (95% CI: 4.8, 7.8%). An IQR increment in tibia bone Pb (14 μg/g) was associated with a 3.7% higher homocysteine (95% CI: 1.6, 5.6%), which was attenuated to 1.5% (95% CI: –0.5, 3.6%) after adjusting for blood Pb. For comparison, a 5-year increase in time from baseline was associated with a 5.7% increase in homocysteine (95% CI: 4.3, 7.1%). The association between blood Pb and homocysteine was significantly stronger among participants with estimated dietary intakes of vitamin B₆ and folate below (vs. above) the study population medians, which were similar to the U.S. recommended dietary allowance intakes.Conclusions: Pb exposure was positively associated with plasma homocysteine concentration. This association was stronger among men with below-median dietary intakes of vitamins B₆ and folate. These findings suggest that increasing intake of folate and B₆ might reduce Pb-associated increases in homocysteine, a risk factor for cardiovascular disease and neurodegeneration.Citation: Bakulski KM, Park SK, Weisskopf MG, Tucker KL, Sparrow D, Spiro A III, Vokonas PS, Nie LH, Hu H, Weuve J. 2014. Lead exposure, B vitamins, and plasma homocysteine in men 55 years of age and older: the VA Normative Aging Study. Environ Health Perspect 122:1066–1074; http://dx.doi.org/10.1289/ehp.1306931     

Biological Variability and Impact of Oral Contraceptives on Vitamins B6, B12 and Folate Status in Women of Reproductive Age

Vitamins B₆, B₁₂ and folate play crucial metabolic roles especially during the reproductive years for women. There is limited reporting of within-subject variability of these vitamins. This study aimed to determine the within and between subject variability in serum vitamins B₆, B₁₂, folate and erythrocyte folate concentrations in young women; identify factors that contribute to variability; and determine dietary intakes and sources of these vitamins. Data were obtained from the control group of a trial aimed at investigating the effect of iron on the nutritional status of young women (age 25.2 ± 4.2 year; BMI 21.9 ± 2.2 kg/m²). The coefficients of variability within-subject (CV_I) and between-subject (CV_G) for serum vitamins B₆, B₁₂ and folate, and erythrocyte folate were calculated. Food frequency questionnaires provided dietary data. CV_I and CV_G were in the range 16.1%–25.7% and 31.7%–62.2%, respectively. Oral contraceptive pill (OCP) use was associated (P = 0.042) with lower serum vitamin B₁₂ concentrations. Initial values were 172 ± 16 pmol/L and 318 ± 51 pmol/L for OCP and non-OCP users, respectively; with differences maintained at four time points over 12 weeks. BMI, age, physical activity, alcohol intake and haematological variables did not affect serum or erythrocyte vitamin concentrations. Vitamin B₁₂ intakes were derived from traditional and unexpected sources including commercial energy drinks. Young women using OCP had significantly lower serum vitamin B₁₂ concentrations. This should be considered in clinical decision making and requires further investigation.     

Poor nutrition and alcohol consumption are related to high serum homocysteine level at post-stroke

BACKGROUND/OBJECTIVES

Increased serum homocysteine (Hcy) levels have been reported to be related to the occurrence of cardio- and cerebrovascular diseases. High serum Hcy levels are also related to the development of secondary stroke and all-cause mortality. The purpose of this study was to investigate the prevalence of high serum homocysteine level and relating factors, and the change over the 10 month period post-stroke.

SUBJECTS/METHODS

Consecutive stroke patients who were admitted to the Asan Medical Center were enrolled. Ten months after the onset of stroke, an interview with a structured questionnaire was performed and blood samples were obtained for the biochemical parameters. Nutritional status was determined using the mini nutritional assessment (MNA) score and dietary nutrient intakes were also obtained using a 24 hour recall method.

RESULTS

Out of 203 patients, 84% were malnourished or at risk of malnutrition, and 26% had high homocysteine levels at 10 months post-stroke. Using logistic regression, the factors related with high homocysteine levels at 10 months post-stroke included heavy alcohol consumption (P = 0.020), low MNA scores (P = 0.026), low serum vitamin B₁₂ (P = 0.021) and low serum folate levels (P = 0.003). Of the 156 patients who had normal homocysteine levels at admission, 36 patients developed hyperhomocysteinemia 10 months post-stroke, which was related to heavy alcohol consumption (P = 0.013). Persistent hyperhomocysteinemia, observed in 22 patients (11%), was related to male sex (P = 0.031), old age (P = 0.042), low vitamin B₆ intake (P = 0.029), and heavy alcohol consumption (P = 0.013).

CONCLUSION

Hyperhomocysteinemia is common in post-stroke, and is related to malnutrition, heavy alcohol drinking and low serum level of folate and vitamin B₁₂. Strategies to prevent or manage high homocysteine levels should consider these factors.