Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials

L Brattstrom, F Landgren, B Israelsson, A Lindgren, B Hultberg, A Andersson, G Cuskelly, H McNulty, SS Strain, J McPartlin, DG Weir, JM Scott, M den Heijer, IA Brouwer, HJ Blom, GMJ Bos, A Spaans, FR Rosendaal, CMG Thomas, HL HaakPW Wijermans, WBJ Gerrits, HJ Naurath, E Joosten, R Riezler, SP Stabler, RH Allen, J Lindenbaum, K Pietrzik, R Prinz-Langenohl, J Dierkes, E Saltzman, JB Mason, P Jacques, J Selhub, D Salem, E Schaefer, IH Rosenberg, J Ubbink, A van der Mere, WJH Vermack, R Delport, PJ Becker, HC Potgieter, JV Woodside, JWG Yarnell, D McMaster, IS Young, EE McCrum, SS Patterson, KF Gey, AE Evans, R Clarke, P Appleby, P Harding, P Sherliker, R Collins, C Frost, V Leroy

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1117 Citations (Scopus)


Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6. Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentrations. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. Subjects: Individual data on 1114 people included in 12 trials. Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P < 0.001) and at lower pretreament blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 mu mol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P < 0.001), with similar effects 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 homocysteine, Vitamin B-6 (mean 16.5 mg daily) did not have a significant additional effect. Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by 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 risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.
Original languageEnglish
Pages (from-to)894-898
Issue number7135
Publication statusPublished (in print/issue) - Mar 1998


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