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Department of Food Technology and Nutrition Sciences (P.W.S., P.V., F.J.K.), Division of Human Nutrition and Epidemiology, Wageningen Agricultural University, Wageningen, THE NETHERLANDS
Netherlands Institute of Health Sciences (P.W.S.), Erasmus University Medical School, Rotterdam, THE NETHERLANDS
Institute of Human Nutrition (P.W.S.), Columbia University, New York, New York
Address reprint requests to: Petra Verhoef, PhD, Department of Food Technology and Nutrition, Division of Human Nutrition and Epidemiology, Wageningen Agricultural University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands
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 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 B12 and erythrocyte folate concentrations showed statistically significantly lower tHcy concentrations (-4.00 and -4.71 µmol/L, respectively) than those in the lowest quartile. Referents in the upper quartile of plasma B6 showed significantly lower tHcy concentrations (-2.36 µmol/L) than referents in the lowest quartile. Subjects in the lowest quartile of vitamin B12 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 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.
Key words: vitamin B6, vitamin B12, folate, plasma total homocysteine, coronary atherosclerosis, methylenetetrahydrofolate reductase (MTHFR)
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