Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials

Background: Dietary supplementation with B vitamins that lower blood homocysteine concentrations is expected to reduce cardiovascular disease risk, but there has been uncertainty about the optimum regimen to use for this purpose. Objective: The objectives were to ascertain the lowest dose of folic acid associated with the maximum reductionin homocysteine concentrations and to determine the additional relevance of vitamins B-12 and B-6. Design: A meta-analysis of 25 randomized controlled trials involving individual data on 2596 subjects assessed the effect on plasma homocysteine concentrations of different doses of folic acid and of the addition of vitamins B-12 and B-6. Results: The proportional reductions in plasma homocysteine concentrations produced by folic acid were greater at higher homocysteine (P = 0.8 mg folic acid are typically required to achieve the maximal reduction in plasma homocysteine concentrations producedby folic acid supplementation. Doses of 0.2 and 0.4 mg are associated with 60% and 90%, respectively, of this maximal effect.