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

Objectives: To investigate the association of status of vitamins B-6, B-12 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 angiographically-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 B-12 and erythrocyte folate concentrations showed statistically significantly lower tHcy concentrations (-4.00 and -4.71 mu mol/L, respectively) than those in the lowest quartile. Referents in the upper quartile of plasma B-6 showed significantly lower tHcy concentrations (-2.36 mu mol/L) than referents in the lowest quartile. Subjects in the lowest quartile of vitamin B-12 concentration 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 B-6 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 B-12 concentration is a risk factor for coronary atherosclerosis, independently of tHcy. Conclusion: The presently accepted view that vitamin B-6 mainly affects tHcy after methionine loading, and not fasting tHcy, is contradicted by our findings in referents. Low vitamin B-12 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.