Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status

Objective

Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians.

Design

Double-blind, placebo controlled, randomised crossover study.

Setting

Community dwelling vegetarians.

Participants

Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. Intervention: Vitamin B-12 (500??g/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41).

Measurement

How-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound.

Results

The mean age of the subjects was 45+9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (??=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028).

Conclusions

Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.     

Dietary intake of vitamin B-6, plasma pyridoxal 5'-phosphate, and homocysteine in Puerto Rican adults

Background

Vitamin B-6 is an important cofactor in many metabolic processes. However, vitamin B-6 intake and plasma status have not been well studied in the Puerto Rican population, a group with documented health disparities.

Objective

To assess dietary intake of vitamin B-6, food sources, and plasma status of pyridoxal 5′-phosphate (PLP), and their associations with plasma homocysteine in 1,236 Puerto Rican adults, aged 45 to 75 years, living in the greater Boston area.

Design

Baseline data were analyzed cross-sectionally.

Method

Questionnaire data were collected by home interview. Dietary intake was assessed with a semiquantitative food frequency questionnaire. Plasma PLP and homocysteine were assayed from blood samples collected in the home.

Results

The mean daily intake of vitamin B-6 was 2.90±1.28 mg for men and 2.61±1.29 mg for women (P<0.001). Approximately 11% were deficient (PLP <4.94 ng/mL [PLP <20 nmol/L]) and another 17% insufficient (PLP ≥4.94 but <7.41 ng/mL [PLP ≥20 but <30 nmol/L]). Household income below the poverty threshold, physical inactivity, and current smoking were significantly associated with lower plasma PLP (P<0.05). Food groups contributing most to vitamin B-6 intake included ready-to-eat cereals, poultry, rice, potatoes, and dried beans. However, only intake of ready-to-eat cereals and use of supplements with vitamin B-6 were significantly associated with plasma PLP sufficiency (≥7.41 vs <7.41 ng/mL [PLP ≥30 vs <30 nmol/L], P<0.01). Both vitamin B-6 intake and PLP were significantly associated with plasma total homocysteine (P<0.001). The association between PLP and homocysteine remained statistically significant after further adjustment for plasma vitamin B-12 and folate (P=0.028).

Conclusions

Given the known importance of vitamin B-6 to health, the high prevalence of low vitamin B-6 status in this Puerto Rican population is of concern. Further work is needed to clarify the potential role that insufficient vitamin B-6 may have in relation to the observed health disparities in this population.     

Effects of folate, vitamin B-12 and vitamin B-6 supplementation on methionine-induced hyperhomocysteinemia in rats

An excessive intake of dietary methionine increases plasma total homocysteine (tHcy, an independent risk factor for premature cardiovascular disease) by enhancing the synthesis of homocysteine. Information on the influence of excess dietary vitamins involved in homocysteine metabolism on the methionine-induced hyperhomocysteinemia is, however, limited. Thus, a six-week study was conducted to determine the influence of excess folic acid, vitamin B-12 and vitamin B-6 on the methionine-induced hyperhomocysteinemia in rats. Supplementation of the casein control diet with 10 and 20 g/kg L-Met increased plasma tHcy to 2.0 and 8.0 times control, respectively. The hyperhomocysteinemia caused by the addition of 10 g/kg L-Met to the control diet, was completely counteracted by extra folic acid or three vitamins combined (folic acid, 2 mg/kg; vitamin B-12, 25 μg/kg; plus vitamin B-6, 6 mg/kg) but the addition of extra vitamin B-12 or vitamin B-6 alone had no effect on plasma tHcy. Similarly, extra dietary folic acid or the three vitamins combined caused substantial reduction in plasma tHcy of rats fed the control diet supplemented with 20 g/kg L-Met but addition of vitamin B-12 or vitamin B-6 alone exacerbated plasma tHcy.     

Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations.

The catabolism of homocysteine through cystathionine synthesis requires pyridoxal-5'-phosphate, thus the effect of vitamin B-6 deficiency on plasma homocysteine concentrations was evaluated. Total fasting plasma homocysteine concentrations were measured in 11 elderly subjects aged 64.4 +/- 1.7 y (mean +/- SE) who consumed a vitamin B-6-deficient diet for less than or equal to 20 d. Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency. In a supporting study, fasting plasma homocysteine concentrations were measured in 3- and 23-mo-old rats fed vitamin B-6-deficient diets and were compared with those of vitamin B-6-replete, pair-fed controls. There was no difference in homocysteine concentrations between deficient and pair-fed animals after 6 wk of the dietary regimen for either age group; after 9 wk a modest elevation was observed in the 3-mo-old deficient rats whereas no difference was observed for the 23-mo-old rats. It is concluded that fasting plasma homocysteine concentrations are not initially elevated in vitamin B-6 deficiency and therefore fasting plasma homocysteine concentrations are not a good indicator of vitamin B-6 status.     

Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis

OBJECTIVE: The purpose of this study was to determine if nonsupplementing older women (aged >or=55 years) with rheumatoid arthritis had higher plasma homocysteine and lower B-vitamin status compared to healthy controls. Elevated plasma homocysteine, a risk factor for cardiovascular disease, may help explain why individuals with rheumatoid arthritis have an increased risk of cardiovascular disease. METHODS: Older, free-living women were classified as rheumatoid arthritis (n=18) or healthy control (n=33). Participants were not using B-vitamin supplements. Fasting blood samples were measured for pyridoxal 5'phosphate (PLP) (the metabolically active coenzyme form of vitamin B-6), folate, red blood cell folate, vitamin B-12, transcobalamin II, homocysteine, C-reactive protein, and lipid concentrations. Participants completed 7-day weighed food records, the Stanford Health Assessment Questionnaire (HAQ), and a visual analog pain scale. RESULTS: PLP concentrations were lower in the rheumatoid arthritis vs healthy control participants (4.93+/-3.85 vs 11.35+/-7.11 ng/mL [20+/-16 vs 46+/-29 nmol/L]; P<0.01) whereas plasma homocysteine was higher in the rheumatoid arthritis group (1.63+/-0.74 vs 1.15+/-0.38 mg/L [12.1+/-5.5 vs 8.5+/-2.8 micromol/L]; P=0.02). Red blood cell folate concentrations were lower in the rheumatoid arthritis vs healthy control participants [414+/-141 vs 525+/-172 ng/mL [938+/-320 vs 1,190+/-390 nmol/L]; P=0.02). No significant differences were found for plasma folate, vitamin B-12, and transcobalamin II. An inverse correlation was found between PLP concentrations and the HAQ disability index (r=-0.37; P<0.01). A positive correlation was found between homocysteine concentrations and the HAQ disability index (r=0.36; P=0.01). Total cholesterol and low-density lipoprotein cholesterol levels were lower in the rheumatoid arthritis group (cholesterol 191+/-43 vs 218+/-33 mg/dL [4.95+/-1.11 vs 5.65+/-0.85 mmol/L]; P=0.02; low-density lipoprotein cholesterol 110+/-36 vs 137+/-29 mg/dL [2.85+/-0.93 vs 3.55+/-0.75 mmol/L]; P<0.01). No significant differences were seen between groups for protein (g/day), fat (g/day), cholesterol (mg/day), folate (microg/day), vitamin B-12 (microg/day), and vitamin B-6 (mg/day) dietary intakes. CONCLUSIONS: Poor vitamin B-6 status and elevated plasma homocysteine concentrations were seen in older women with rheumatoid arthritis compared to healthy controls and may contribute to their increased risk of cardiovascular disease.     

Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women

A well-planned vegetarian diet has been stated to be adequate during pregnancy. The aim of the present study was to compare serum vitamin B-12 and homocysteine concentrations in pregnant women (n = 109) consuming vegetarian and Western diets and to evaluate the adequacy of current dietary reference intakes of vitamin B-12 for these women. Pregnant women adhering to vegetarian diets for at least 3 y, with subgroups of ovo-lacto vegetarians (OLVs; n = 27), low-meat eaters (LME, n = 43), and women eating an average Western diet (control group, n = 39), were recruited. Dietary vitamin B-12 intake, serum vitamin B-12, and plasma total homocysteine (tHcy) concentrations were measured in wk 9-12, 20-22, and 36-38 of pregnancy. During pregnancy serum vitamin B-12 concentrations of ovo-lacto vegetarians (P < 0.001) and low-meat eaters (P = 0.050) were lower than those of the control group. We observed the combination of low serum vitamin B-12 concentrations and elevated plasma tHcy in 22% of ovo-lacto vegetarians, in 10% of low-meat eaters, and in 3% of controls (P = 0.003). In OLVs, serum vitamin B-12 predicted 60% of the plasma tHcy variation (P < 0.001), but in LMEs and controls only <10% (NS). Serum vitamin B-12 concentrations increased and plasma tHcy decreased sharply with increasing dietary intake of vitamin B-12 toward a cutoff point of 3 mug/d. Pregnant women consuming a long-term predominantly vegetarian diet have an increased risk of vitamin B-12 deficiency. Current recommended dietary intakes urgently need reevaluation.     

Effects of a healthy Nordic diet on plasma 25-hydroxyvitamin D concentration in subjects with metabolic syndrome: a randomized,placebo-controlled trial (SYSDIET)

Purpose

At northern latitudes, vitamin D is not synthesized endogenously during winter, causing low plasma 25-hydroxyvitamin D (25(OH)D) concentrations. Therefore, we evaluated the effects of a healthy Nordic diet based on Nordic nutrition recommendations (NNR) on plasma 25(OH)D and explored its dietary predictors.

Methods

In a Nordic multi-centre trial, subjects (n = 213) with metabolic syndrome were randomized to a control or a healthy Nordic diet favouring fish (≥300 g/week, including ≥200 g/week fatty fish), whole-grain products, berries, fruits, vegetables, rapeseed oil and low-fat dairy products. Plasma 25(OH)D and parathyroid hormone were analysed before and after 18- to 24-week intervention.

Results

At baseline, 45 % had vitamin D inadequacy (<50 nmol/l), whereas 8 % had deficiency (<25 nmol/l). Dietary vitamin D intake was increased by the healthy Nordic diet (P < 0.001). The healthy Nordic and the control diet reduced the prevalence of vitamin D inadequacy by 42 % (P < 0.001) and 19 % (P = 0.002), respectively, without between-group difference (P = 0.142). Compared with control, plasma 25(OH)D (P = 0.208) and parathyroid hormone (P = 0.207) were not altered by the healthy Nordic diet. Predictors for 25(OH)D were intake of vitamin D, eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA), vitamin D supplement, plasma EPA and plasma DHA. Nevertheless, only vitamin D intake and season predicted the 25(OH)D changes.

Conclusion

Consuming a healthy Nordic diet based on NNR increased vitamin D intake but not plasma 25(OH)D concentration. The reason why fish consumption did not improve vitamin D status might be that many fish are farmed and might contain little vitamin D or that frying fish may result in vitamin D extraction. Additional ways to improve vitamin D status in Nordic countries may be needed.     

Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial

BACKGROUND: High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease, stroke, and dementia and are relatively common in older adults. OBJECTIVE: We assessed the effect of breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 on vitamin and homocysteine status. DESIGN: A randomized, double-blind trial was conducted in 189 volunteers aged 50-85 y. The subjects had no history of hypertension, anemia, asthma, cancer, or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal. Subjects were randomly assigned to consume 1 cup (0.24 L) breakfast cereal fortified with 440 microg folic acid, 1.8 mg vitamin B-6, and 4.8 microg vitamin B-12 or placebo cereal for 12 wk. Blood was drawn at 0, 2, 12, and 14 wk. Methionine-loading tests were conducted at baseline and week 14. RESULTS: Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group (P < 0.001). The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2% to 0%, with vitamin B-12 concentrations < 185 pmol/L from 9% to 3%, with vitamin B-6 concentrations < 20 nmol/L from 6% to 2%, and with homocysteine concentrations > 10.4 micromol/L (women) or > 11.4 micromol/L (men) from 6.4% to 1.6%. The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased. CONCLUSIONS: In this relatively healthy group of volunteers, consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations, including post-methionine-load homocysteine concentrations.     

Lowering of homocysteine concentrations in elderly men and women.

B-vitamin supplementation has previously been shown to lower the concentration of plasma total homocysteine, a risk factor for cardiovascular disease. Little is known about the homocysteine-lowering effects of low-dose B-vitamins in elderly individuals, who are prone to higher homocysteine levels due to advanced age and a greater frequency of impaired vitamin status. We aimed to identify if and to what extent B-vitamins lower total homocysteine and its subfractions in elderly individuals. Men and women (> or = 60 years) received either B-vitamins (400 micrograms folic acid + 1.65 mg pyridoxine + 3 micrograms cyanocobalamin) or a placebo daily for 4 weeks. Subjects in the vitamin group showed a significant decrease in plasma total homocysteine during the first 2 weeks; thereafter, total homocysteine only slightly decreased further resulting in a geometric mean reduction of -16.3% (95% CI: -11.3% to -21.0%) over the entire treatment period. Free homocysteine decreased as well. However, the observed higher ratio of free/total homocysteine after 4 weeks of supplementation suggest a more pronounced reduction in protein-bound homocysteine. Low-dose B-vitamin supplementation is effective in lowering homocysteine in elderly individuals. Further studies are needed to be able to depict the effect of B-vitamin supplementation on different homocysteine sub-fractions in plasma.     

Dietary Intakes of Vitamin B-2 (Riboflavin), Vitamin B-6, and Vitamin B-12 and Ovarian Cycle Function among Premenopausal Women

BackgroundRiboflavin, vitamin B-6, and vitamin B-12 are key players in one-carbon metabolism as enzymatic cofactors, and deficiency of these nutrients may influence reproductive outcomes possibly through affecting reproductive hormones.ObjectiveThe goal was to investigate associations between dietary intakes of riboflavin, vitamin B-6, and vitamin B-12, and menstrual function among premenopausal women.DesignThis was a secondary analysis of a prospective cohort study conducted at the University at Buffalo during 2005 to 2007.Participants/settingParticipants were 259 healthy, regularly menstruating women (aged 18 to 44 years) with self-reported menstrual cycles between 21 and 35 days, who were not trying to conceive, and who had not used hormonal contraception during the past 3 months.Main outcome measuresIntakes of B vitamins were assessed via 24-hour dietary recalls four times per menstrual cycle for two cycles. Serum reproductive hormones and plasma homocysteine were measured eight and three times, respectively, per cycle for two cycles. Anovulatory cycles were determined by progesterone concentrations ≤5 ng/mL (15.9 nmol/L) and no observed serum luteinizing hormone peak during the mid or late luteal phase visit.Statistical analysisWeighted linear mixed regressions were used to evaluate associations between cycle-averaged B vitamin intakes and hormones and homocysteine, and generalized linear regressions for associations with anovulation. Models were adjusted for age, race, body mass index, physical activity, alternate Mediterranean diet score, intakes of total energy, protein, fiber, and folate, and percentage of energy intake from fat.ResultsHigher intakes of riboflavin (per 0.1 mg increase in intake) were inversely correlated with estradiol (−0.87%, 95% CI −1.67 to −0.06) and homocysteine levels (−0.61%, 95% CI −1.10 to −0.12). Higher vitamin B-6 intakes were suggestive of higher follicle-stimulating hormone, although the results were not statistically significant (0.63% difference, 95% CI −0.03 to 1.29, per 0.1 mg increase in intake; P=0.06). Small increases in testosterone and decreases in homocysteine were found with vitamin B-12 intake. No associations were observed between intake of B vitamins and a risk of sporadic anovulation.ConclusionsHigher intakes of riboflavin were associated with a small decrease in serum estradiol among healthy, regularly menstruating women. Higher intakes of riboflavin and vitamin B-12 were associated with lower plasma homocysteine concentrations. Overall, riboflavin, vitamin B-6, and vitamin B-12 that are one-carbon nutrients do not appear to influence the ovarian cycle among premenopausal women.     

Factors affecting the accumulation of homocyst(e)ine in rats deficient in vitamin B-6

Factors that may affect the concentration of accumulated homocyst(e)ine in rats deficient in vitamin B-6 were studied. Hepatic cystathionine synthase activity in vitamin B-6 deficient rats was 41.5% of control and plasma protein-bound and free homocyst(e)ine concentrations were significantly increased; however, among deficient rats there was no correlation between the concentration of homocyst(e)ine and the activity of hepatic cystathionine synthase. The plasma protein-bound homocysteine concentration did not fluctuate with time of day, but a decrease in bound homocysteine was found when blood was sampled repeatedly from the same animal during a 24-hour period. A 24-hour fast resulted in a reduction in plasma homocyst(e)ine to concentrations not different from those of control animals. The protein content of the diet affected growth but not food intake of rats. Feeding a 10% versus a 60% casein diet did not change the concentration of accumulated homocyst(e)ine. Of the factors examined, only food restriction significantly affected plasma homocyst(e)ine concentration in rats deficient in vitamin B-6. It is speculated that decreased and sporadic food intake in rats deficient in vitamin B-6 may be responsible for the large fluctuations in homocyst(e)ine concentration observed in these animals over time.     

Hyperhomocysteinemia is associated with vitamin B-12 deficiency: A cross-sectional study in a rural,elderly population of Shanxi China

Objectives

To report the association of lifestyle factors and plasma vitamin B-12 with hyperhomocysteinemia in a large sample of men and women living in a region of China where there is an increased risk of NTDs.

Design

Community-based, cross-sectional study of Lvliang City, Shanxi Province, China.

Setting

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) and a sensitive marker of vitamin B-12 and folate deficiency.

Participants

A total of 2355 (1044 men and 1311 women) participants born before 1 January 1958 (≥55 years of age) and living in Lvliang City for at least 2 months a year were included.

Measurements

The participants were assessed regarding demographic characteristics, height, weight, as well as having a physical examination and blood sampling for serum cholesterol, total homocysteine (tHcy), folate, and vitamin B12 levels.

Results

The median (25th–75th percentile) tHcy concentration was 21.5 (15.8–33.6) µmol/L in men and 18.0 (13.4–24.8) µmol/L in women. The overall prevalence of hyperhomocysteinemia (tHcy ≥15 µmol/L) was 72.6% (84.3% in men and 63.2% in women), inversely correlated with folate (r=–0.230, P=0.006) and vitamin B-12 (r=–0.540, P<0.001), and positively correlated with uric acid (r=0.054, P<0.001). Vitamin B-12 and folate deficiency, older age, and male gender were associated with elevated tHcy; with vitamin B-12 deficiency being the strongest.

Conclusions

Plasma tHcy concentration and hyperhomocysteinemia were significantly higher in this population than in previously studied populations. Vitamin B-12 and folate supplementation, concomitant lifestyle changes such as smoking cessation, and lipid-lowering treatments may help to decrease plasma tHcy concentrations and reduce the CVD risk in this population.

     

Konjac mannan improves the vitamin B-6 status of rats fed a vitamin B-6-deficient diet

To investigate how dietary fiber in the diet affects vitamin B-6 nutriture of rats which have been deprived of vitamin B-6, rats were made vitamin B-6-deficient by feeding a vitamin B-6-deficient 70% casein diet. They were fed 2% cellulose powder-based vitamin B-6-deficient diets supplemented with 3% of additional dietary fiber sources (agar, konjac mannan, pectin and cellulose powder) for subsequent 18 days. Vitamin B-6 status was evaluated according to several biological criteria (weight gain, urinary excretion of xanthurenic acid after tryptophan loading, plasma pyridoxal 5'-phosphate, apparent pyridoxal 5'-phosphate-saturation of liver kynureninase, urinary excretion of 4-pyridoxic acid and fecal output of vitamin B-6). Vitamin B-6 status evaluated by these criteria was considerably improved in the konjac mannan-fed group, when compared with the respective data of the vitamin B-6 supplemented group. The relative mean effect of the konjac mannan diet was about 40% of the vitamin B-6 supplemented diet. In conclusion, konjac mannan was effective for improving the vitamin B-6 nutritional state in vitamin B-6-deprived rats.     

Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine,but not cognitive performance

Background

Suboptimal vitamin B status might affect cognitive performance in early childhood. We tested the hypothesis that short-term supplementation with folic acid and selected B vitamins improves cognitive function in healthy children in a population with relatively low folate status.

Methods

We screened 1,002 kindergarten children for suboptimal folate status by assessing the total urinary para-aminobenzoylglutamate excretion. Two hundred and fifty low ranking subjects were recruited into a double blind, randomized, controlled trial to receive daily a sachet containing 220 μg folic acid, 1.1 mg vitamin B₂, 0.73 mg B₆, 1.2 μg B₁₂ and 130 mg calcium, or calcium only for 3 months. Primary outcomes were changes in verbal IQ, short-term memory and processing speed between baseline and study end. Secondary outcomes were urinary markers of folate and vitamin B₁₂ status, acetyl-para-aminobenzoylglutamate and methylmalonic acid, respectively, and, in a subgroup of 120 participants, blood folate and plasma homocysteine.

Results

Pre- and post-intervention cognitive measurements were completed by 115 children in the intervention and 122 in the control group. Compared to control, median blood folate increased by about 50 % (P for difference, P < 0.0001). Homocysteine decreased by 1.1 μmol/L compared to baseline, no change was seen in the control group (P for difference P < 0.0001) and acetyl-para-aminobenzoylglutamate was 4 nmol/mmol higher compared to control at the end of the intervention (P < 0.0001). We found no relevant differences between the groups for the cognitive measures.

Conclusion

Short-term improvement of folate and homocysteine status in healthy children does not appear to affect cognitive performance.     

The status of plasma homocysteine and related B-vitamins in healthy young vegetarians and nonvegetarians

Summary. Background: Exclusion of animal products and having only plant protein in vegetarian diets may affect the status of certain B-vitamins, and further cause the elevation of plasma homocysteine concentration. Aim: The purpose of this study was to assess the status of homocysteine and related B-vitamins in vegetarians and nonvegetarians. The effects of biochemical parameters of B-vitamins and dietary protein on plasma homocysteine were also examined. Methods: The study was performed at the Chung Shan Medical University, Taichung, in the central part of Taiwan. Thirty-seven vegetarians (28.9 ± 5.5 y) and 32 nonvegetarians (22.9 ± 1.6 y) were recruited. Nutrient intake was recorded using 3-day dietary records. Fasting venous blood samples were obtained. Plasma homocysteine, folate and vitamin B-12 were measured. Vitamin B-6 status was assessed by direct measures [plasma pyridoxal 5'-phosphate (PLP) and urinary 4-pyridoxic acid (4-PA)] and indirect measures [erythrocyte alanine (EALT-AC) and aspartate (EAST-AC) aminotransaminase activity coefficient]. Results: There was no significant difference in vitamin B-6 intake between the two groups, although the vegetarian group had a significantly lower vitamin B-12 intake than the nonvegetarian group. Vegetarian subjects had significantly lower mean plasma PLP and vitamin B-12 concentrations than did nonvegetarian subjects (p < 0.05); however, a significantly higher mean plasma folate concentration was found in the vegetarian group. Vegetarian subjects had a significantly higher mean plasma homocysteine concentration than nonvegetarian subjects (13.2 ± 7.9 vs. 9.8 ± 2.2 μmol/L). Negative correlations were seen between plasma homocysteine and vitamin B-12 concentrations in the vegetarian (p = 0.004), nonvegetarian (p = 0.026), and pooled (p < 0.001) groups. From best subsets regression analyses, the plasma homocysteine concentration could be significantly predicted by total protein intake (p = 0.027) and plasma vitamin B-12 concentration (p = 0.005) in the pooled group. When the intake of protein is not considered, vitamin B-12 concentration is still a strong predictor of plasma homocysteine concentration (p = 0.012). Conclusions: Vitamin B-12 intake and mean plasma vitamin B-12 concentration were lower for vegetarian subjects than for nonvegetarian subjects, leading to an increase in plasma homocysteine concentration. Vitamin B-6 and folate had little effect on plasma homocysteine concentration when individuals had adequate vitamin B-6 and folate status. Received: 15 July 2002, Accepted: 24 October 2002 The study was supported by National Science Council (NSC 89–2320-B-040–046), Taiwan. Correspondence to: Y. C. Huang     

Plasma homocysteine, but not folate or vitamin B-12, predicts mortality in older people in the United Kingdom

There is uncertainty about the importance of plasma levels of homocysteine, vitamin B-12, and folate for all-cause and cardiovascular disease (CVD) mortality in older people. We examined the associations between plasma levels of folate, vitamin B-12, and homocysteine, and all-cause and CVD mortality among community-dwelling adults aged > or = 75 y living in the United Kingdom. In a population-based prospective cohort study, 853 men and women aged > or = 75 y were examined in 1995-98 as part of the Medical Research Council Trial of Assessment and Management of Older People in the Community. During a median follow-up of 7.6 y (5528 person-years of follow-up), 429 individuals (50.3%) died, including 185 from CVD. Individuals with plasma homocysteine levels in the top one-third compared with the bottom one-third had a 2-fold higher risk of all-cause mortality (hazard ratio, 2.20; 95% CI, 1.76, 2.75; P < 0.001) and CVD mortality (hazard ratio, 1.96; 95% CI, 1.39, 2.78; P < 0.001) after adjustment for age, sex, and other covariates. There was no association of plasma folate or vitamin B-12 levels with mortality. Our results extend previously reported associations of homocysteine with mortality, and the absence of associations of folate and vitamin B-12 with mortality, to the older population.     

Folate and vitamin B12 improved alcohol-induced hyperhomocysteinemia in rats

Objective

The purpose of this study was to investigate the protective effects of combined treatment of folate and vitamin B12 against alcoholic liver disease.

Methods

Male Wistar rats weighing about 160 g were divided into four groups: an ethanol group fed an ethanol liquid diet; a control group pair-fed an isoenergetic diet without ethanol; an ethanol and vitamin group fed an ethanol-containing diet that was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day); and a control and vitamin group fed an isoenergetic diet without ethanol, which was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day).

Results

After 16 wk, the plasma folate concentration in the ethanol group was significantly lower than in the other three groups. The plasma homocysteine concentration in the ethanol group was significantly higher than in the other three groups. The hepatic matrix metalloproteinase-2 concentration in the ethanol group was significantly higher than in the control and ethanol/vitamin groups. Furthermore, the plasma homocysteine concentration at the 16th week and the hepatic matrix metalloproteinase-2 concentration showed a significant positive correlation in rats of each group. In addition, pathologic evidence of liver fibrosis was observed only in the ethanol group. Furthermore, hepatic cytochrome 2E1 protein expression in group E increased significantly.

Conclusion

These results suggest that combined treatment of folate and vitamin B12 can alleviate alcoholic liver injury that may be related to normalization of plasma homocysteine levels.     

Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet

Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease. Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies, no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine. We determined whether a multivitamin/mineral supplement formulated at about 100% Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid. In this randomized, double-blind, placebo-controlled trial, 80 free-living men and women aged 50-87 y with total plasma homocysteine concentrations of > or =8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet. After the 8-wk treatment, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P: < 0.01). Plasma folate, pyridoxal phosphate (PLP) and vitamin B-12 concentrations were increased 41.6, 36.5 and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group. The mean homocysteine concentration decreased 9.6% in the supplemented group (P: < 0.001) and was unaffected in the placebo group. There were no significant changes in dietary intake during the intervention. Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet.     

Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism

BACKGROUND: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction. OBJECTIVES: The objectives were to assess the influence of the TC 776C--> G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphisms and vitamin B-12 status on homocysteine concentrations. DESIGN: Healthy, nonpregnant women (n = 359; aged 20-30 y) were screened to determine plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC 776C-->G and MTHFR 677C-->T genotypes. RESULTS: The serum holo-TC concentration for women with the variant TC 776 GG genotype was significantly different (P = 0.0213) from that for subjects with the CC genotype (74 +/- 37 and 87 +/- 33 pmol/L, respectively). An inverse relation was observed between plasma homocysteine concentrations and both serum holo-TC (P G polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.     

Dietary vitamin B-6 restriction does not alter rates of homocysteine remethylation or synthesis in healthy young women and men

BACKGROUND: The effects of vitamin B-6 status on steady-state kinetics of homocysteine metabolism in humans are unclear. OBJECTIVE: The objective was to determine the effects of dietary vitamin B-6 restriction on the rates of homocysteine remethylation and synthesis in healthy humans. DESIGN: Primed, constant infusions of [(13)C(5)]methionine, [3-(13)C]serine, and [(2)H(3)]leucine were conducted in healthy female (n=5) and male (n=4) volunteers (20-30 y) before and after 4 wk of dietary vitamin B-6 restriction (<0.5 mg vitamin B-6/d) to establish whether vitamin B-6 status affects steady-state kinetics of homocysteine metabolism in the absence of concurrent methionine intake. Effects of dietary vitamin B-6 restriction on vitamin B-6 status, plasma amino acid concentrations, and the rates of reactions of homocysteine metabolism were assessed. RESULTS: Dietary vitamin B-6 restriction significantly reduced plasma pyridoxal 5-phosphate (PLP) concentrations (55.1 +/- 8.3 compared with 22.6 +/- 1.3 nmol/L; P=0.004), significantly increased plasma glycine concentrations (230 +/- 14 compared with 296 +/- 15; P=0.008), and significantly reduced basal (43%; P < 0.001) and PLP-stimulated (35%; P=0.004) lymphocyte serine hydroxymethyltransferase activities in vitro. However, the in vivo fluxes of leucine, methionine, and serine; the rates of homocysteine synthesis and remethylation (total and vitamin B-6-dependent); and the concentrations of homocysteine, methionine, and serine in plasma were not significantly affected by dietary vitamin B-6 restriction. CONCLUSIONS: Moderate vitamin B-6 deficiency does not significantly alter the rates of homocysteine remethylation or synthesis in healthy young adults in the absence of dietary methionine intake.