Nutritional Deficiencies - Health Concerns

B Vitamins - updated: 01 December 2008

Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y

Am J Clin Nutr. 2001 Jun;73(6):1027-33

de Bree A, Verschuren WM, Blom HJ, Kromhout D.

BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration is associated with an increased risk of cardiovascular diseases. Folate, riboflavin, vitamin B-6, and vitamin B-12 are essential in homocysteine metabolism. OBJECTIVE: The objective was to describe the association between dietary intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and the nonfasting plasma tHcy concentration. DESIGN: A random sample of 2435 men and women aged 20-65 y from a population-based Dutch cohort examined in 1993-1996 was analyzed cross-sectionally. RESULTS: Univariately, intakes of all B vitamins were inversely related to the plasma tHcy concentration. In multivariate models, only folate intake remained inversely associated with the plasma tHcy concentration. Mean plasma tHcy concentrations (adjusted for intakes of riboflavin, vitamin B-6, vitamin B-12, and methionine and for age, smoking, and alcohol consumption) in men with low (first quintile: 161 microg/d) and high (fifth quintile: 254 microg/d) folate intakes were 15.4 and 13.2 micromol/L, respectively; in women, plasma tHcy concentrations were 13.7 and 12.4 micromol/L at folate intakes of 160 and 262 microg/d, respectively. In men, the difference in the mean plasma tHcy concentration between men with low and high folate intakes was greater in smokers than in nonsmokers (2.8 compared with 1.6 micromol/L) and greater in nondrinkers than in drinkers of >2 alcoholic drinks/d (3.5 compared with 1.4 micromol/L). In women, the association between folate intake and plasma tHcy was not modified by smoking or alcohol consumption. CONCLUSIONS: In this Dutch population, folate was the only B vitamin independently inversely associated with the plasma tHcy concentration. Changing dietary habits may substantially influence the plasma tHcy concentration in the general population.

Publication Types:

• random sample of 2435 men and women

Dietary intake of folate equivalents and risk of myocardial infarction in the European Prospective Investigation into Cancer and Nutrition (EPIC)--Potsdam study

Public Health Nutr. 2006 Jun;9(4):465-71

Drogan D, Klipstein-Grobusch K, Dierkes J, Weikert C, Boeing H.

OBJECTIVE: To assess the relationship between intake of dietary folate equivalents and risk of myocardial infarction in a German cohort. DESIGN: Intake of dietary folate equivalents was assessed by a validated food-frequency questionnaire. Cox proportional hazard models were used to evaluate the association between intake of dietary folate equivalents and risk of myocardial infarction. SETTING: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, Germany. SUBJECTS: Subjects were 22,245 apparently healthy non-users of vitamin supplements aged 35-64 years. RESULTS: During 4.6 years of follow-up, 129 incident cases of myocardial infarction were identified. Compared with intake below the median (103 microg), higher intake of dietary folate equivalents was associated with a multivariate-adjusted hazard ratio (HR) of 0.57 (95% confidence interval (CI) 0.36-0.91). The inverse association of folate intake and myocardial infarction risk was stronger in participants with an ethanol intake equal to or above the sex-specific median (HR=0.37, 95% CI 0.18-0.79) and attenuated in those with a low ethanol intake (HR=0.67, 95% CI 0.37-1.22). CONCLUSION: An increased intake of dietary folate equivalents was observed to be associated with decreased risk of myocardial infarction in a German study population, pointing towards the importance of folate intake with respect to primary prevention of myocardial infarction.

Publication Types:

• cohort

Vitamins B6, B12, and folate: association with plasma total homocysteine and risk of coronary atherosclerosis

J Am Coll Nutr. 1998 Oct;17(5):435-41

Siri PW, Verhoef P, Kok FJ.

OBJECTIVES: To investigate the association of status of vitamins B6, B12 and folate with plasma fasting total homocysteine (tHcy) and with risk of coronary atherosclerosis; and to establish whether associations between vitamins and risk of coronary atherosclerosis are mediated by tHcy. METHODS: The study population consisted of 131 patients with angiography-defined severe coronary atherosclerosis and 88 referents with no or minor coronary stenosis. Previous analyses in this study population have shown that fasting tHcy is an independent risk factor for coronary atherosclerosis. In the present analyses, using multiple linear regression, we estimated differences in tHcy concentrations between subjects in the lowest and highest quartiles of concentrations of each of the vitamins, adjusting for age, gender, total:HDL cholesterol ratio, smoking habits, alcohol intake, blood pressure, serum creatinine, body mass index and the two other vitamins. We used logistic regression analysis conditional on the set of potential confounders described above to study the association between vitamin concentration and risk of coronary atherosclerosis. By comparing these estimated odds ratios (ORs) with those that were additionally adjusted for fasting tHcy, we determined whether the vitamins exerted their effects on disease risk via homocysteine metabolism. RESULTS: Cases who were in the upper quartile of serum vitamin B12 and erythrocyte folate concentrations showed statistically significantly lower tHcy concentrations (-4.00 and -4.71 mumol/L, respectively) than those in the lowest quartile. Referents in the upper quartile of plasma B6 showed significantly lower tHcy concentrations (-2.36 mumol/L) than referents in the lowest quartile. Subjects in the lowest quartile of vitamin B12 concentrations had higher risk of coronary atherosclerosis (OR: 2.91; 95% CI: 1.10, 7.71) compared to those in the highest quartile. The ORs and 95% CIs for low B6 and low folate were 0.86 (95% CI: 0.33, 2.22) and 0.58 (95% CI: 0.23, 1.48), respectively. Additional adjustment for fasting tHcy weakened associations, although data indicated that low vitamin B12 concentration is a risk factor for coronary atherosclerosis, independently of tHcy. CONCLUSION: The presently accepted view that vitamin B6 mainly affects tHcy after methionine loading, and not fasting tHcy, is contradicted by our findings in referents. Low vitamin B12 concentrations were associated with an increased risk of coronary atherosclerosis, partly independently of tHcy. Although low folate status was a strong determinant of elevated tHcy concentrations, it was not associated with increased risk of coronary atherosclerosis.

Publication Types:

• Case Control

Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis

Arterioscler Thromb Vasc Biol. 1997 May;17(5):989-95

Verhoef P, Kok FJ, Kruyssen DA, Schouten EG, Witteman JC, Grobbee DE, Ueland PM, Refsum H.

Epidemiological research has shown that elevated plasma total homocysteine (tHcy) is a risk factor for atherosclerotic disease. In the present case-control study, we investigated whether fasting or postmethionine-loading tHcy was a stronger predictor of risk of severe coronary atherosclerosis. Furthermore, we studied levels of B vitamins, which are involved in homocysteine metabolism. Subjects were recruited from men and women, aged 25 to 65 years, who underwent coronary angiography between June 1992 and June 1994 in a hospital in Rotterdam, The Netherlands. Cases (n=131) were defined as those with > or =90% occlusion in one and > or =40% occlusion in a second coronary artery, while control subjects (n=88) had <50% occlusion in only one coronary vessel. In addition, a population-based control group free from clinical cardiovascular disease (n=101) was studied. Coronary patients were studied at least 2.5 months after angiography or other acute illness, such as myocardial infarction. After adjusting for age and sex differences between the groups, cases had 9% (P=.01) higher geometric mean fasting and 7% (P=.04) higher geometric mean postload tHcy than the combined control groups. Despite higher levels of tHcy for cases, their geometric mean levels of red cell folate and pyridoxal 5'-phosphate were higher than for control subjects, whereas plasma vitamin B12 was only slightly lower in cases. The frequency distribution of tHcy values in cases was slightly shifted toward the right, across the entire range, compared with the distribution in the combined control group. This was somewhat more obvious for fasting than postload tHcy levels. The odds ratio (OR) for severe coronary atherosclerosis (case status) for each 1 SD increase in fasting tHcy (5 micromol/L) was 1.3 (95% confidence interval [CI], 1.0-1.6), similar to the OR for each 1 SD increase (12 micromol/L) in postmethionine-loading tHcy (1.3 [95 CI, 1.0-1.7]), after adjustment for sex, age, and other potential confounders. Furthermore, there was a significant linear trend of increasing fasting tHcy with increasing number of occluded arteries (P=.01), correcting for sex, age, and other potential confounders. Our data show a positive association between plasma tHcy and risk of severe coronary atherosclerosis, of similar strength for fasting and postload tHcy levels. The data suggest that the association exists over a wide range of tHcy levels, without a clear cutoff point below which there is no increased risk.

Publication Types:

• Case Control

B-vitamins, homocysteine metabolism and CVD

Proc Nutr Soc. 2004 Nov;63(4):597-603

Strain JJ, Dowey L, Ward M, Pentieva K, McNulty H.

The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6 and riboflavin, that are involved in homocysteine metabolism. Homocysteine is a S-containing amino acid and its plasma concentrations can be raised by various constitutive, genetic and lifestyle factors, by inadequate nutrient status and as a result of systemic disease and various drugs. Hyperhomocysteinaemia is a modest independent predictor of CVD and stroke, but causality and the precise pathophysiological mechanism(s) of homocysteine action remain unproven. The predominant nutritional cause of raised plasma homocysteine in most healthy populations is folate insufficiency. Vitamin B12 and, to a lesser extent, vitamin B6 are also effective at lowering plasma homocysteine, especially after homocysteine lowering by folic acid in those individuals presenting with raised plasma homocysteine. However, riboflavin supplementation appears to be effective at lowering plasma homocysteine only in those individuals homozygous for the T allele of the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. This gene codes for the MTHFR enzyme that produces methyltetrahydrofolate, which, in turn, is a substrate for the remethylation of homocysteine by the vitamin B12-dependent enzyme methionine synthase. Individuals with the MTHFR 677TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.

Publication Types:

• Review

Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease

Neurology. 2006 Jul 25;67(2):315-8

de Lau LM, Koudstaal PJ, Witteman JC, Hofman A, Breteler MM.

BACKGROUND: Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects. Higher dietary intakes of folate, vitamin B12, and vitamin B6 (cofactors in homocysteine metabolism) might decrease the risk of PD through decreasing plasma homocysteine. Moreover, vitamin B6 might influence the risk of PD through antioxidant effects unrelated to homocysteine metabolism and through its role in dopamine synthesis. METHODS: In the Rotterdam Study, a prospective, population-based cohort study of people aged 55 years and older, the authors evaluated the association between dietary intake of folate, vitamin B12, and vitamin B6 and the risk of incident PD among 5,289 participants who were free of dementia and parkinsonism and underwent complete dietary assessment at baseline. PD was assessed through repeated in-person examination and continuous monitoring by computer linkage to medical records. Data were analyzed using Cox proportional hazards regression analysis. RESULTS: After a mean follow-up of 9.7 years, the authors identified 72 participants with incident PD. Higher dietary intake of vitamin B6 was associated with a significantly decreased risk of PD (hazard ratio per SD, 0.69 [95% CI 0.50 to 0.96]; for highest vs lowest tertile, 0.46 [0.22 to 0.96]). Stratified analyses showed that this association was restricted to smokers. No association was observed for dietary folate and vitamin B(12). CONCLUSIONS: Dietary vitamin B6 may decrease the risk of Parkinson disease, probably through mechanisms unrelated to homocysteine metabolism.

Publication Types:

• prospective, population-based cohort study

Publication Types:

• Review