LOWERING BLOOD HOMOCYSTEINE WITH FOLIC-ACID BASED SUPPLEMENTS - METAANALYSIS OF RANDOMIZED TRIALS

Objective: To determine the size of reduction in homocysteine concentr ations produced by dietary supplementation with folic acid and with vi tamins B-12 or B-6. Design: Meta-analysis of randomised controlled tri als that assessed the effects of folic acid based supplements on blood homocysteine concentrations. Multivariate regression analysis was use d to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. Subje cts: Individual data on 1114 people included in 12 trials. Findings: T he proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood h omocysteine concentrations (P < 0.001) and at lower pretreament blood folate concentrations (P < 0.001). After standardisation to pretreatme nt blood concentrations of homocysteine of 12 mu mol/l and of folate o f 12 nmol/l (approximate average concentrations for Western population s), dietary folic acid reduced blood homocysteine concentrations by 25 % (95% confidence interval 23% to 28%; P < 0.001), with similar effect s in the range of 0.5-5 mg folic acid daily, Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction in blood homoc ysteine, Vitamin B-6 (mean 16.5 mg daily) did not have a significant a dditional effect. Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitami n B-12 would be expected to reduce blood homocysteine concentrations b y about a quarter to a third (for example, from about 12 mu mol/l to 8 -9 mu mol/l). Large scale randomised trials of such regimens in high r isk populations are now needed to determine whether lowering blood hom ocysteine concentrations reduces the risk of vascular disease.