The results of dietary intervention trials favor the hypothesis that higher intakes of B-vitamins (folate, vitamin B6 and B12), and subsequently lower total homocysteine (tHcy) concentrations, are causally associated with a decreased risk of vascular disease in patients with cardiovascular diseases (CVD). The same is true for a higher intake of omega-3 fish fatty acids. Yet, the lack of hard end points and/or appropriate study designs precludes a definitive conclusion about causality. In the future, intervention trials with hard end points and randomized double-blind placebo-controlled designs should be able to elucidate the causality problem. There are several pathways by which B-vitamins and omega-3 fatty acids may exert their protective effect on CVD, a common pathway is a beneficial effect on the endothelial function and hemostasis. With respect to synergy between B-vitamins and omega-3 fatty acids, there is no evidence that fish oils have a tHcy-lowering effect beyond the effect of the B-vitamins. Nevertheless, animal studies clearly illustrate that vitamin B6- as well as folate-metabolism are linked with those of long-chain omega-3 fatty acids. Furthermore, a human study indicated synergistic effects of folic acid (synthetic form of folate) and vitamin B6 together with omega-3 fatty acids on the atherogenic index and the fibrinogen concentration. Although these results are promising, they were produced in very small selective study populations. Thus, confirmation in large well-designed intervention trials is warranted.
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de Bree, A., Mennen, L., Hercberg, S. et al. Evidence for a protective (synergistic?) effect of B-vitamins and omega-3 fatty acids on cardiovascular diseases. Eur J Clin Nutr 58, 732–744 (2004). https://doi.org/10.1038/sj.ejcn.1601871
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