Copyright © 2002 by the European Society of Cardiology.
Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease
revised December 31, 2001; accepted January 2, 2002Abstract
Aims To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation.
Methods and Results The PACIFIC study was a double-blind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2·0mg daily, folic acid 0·2mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2·0mg folic acid reduced homocysteine by 1·8µmol.l–1 [95% confidence interval (CI) 1·3–2·3] and 0·2mg reduced homocysteine by 1·2µmol.l–1 (95% CI 0·8–1·7). The higher dose reduced homocysteine significantly more than the lower dose (P=0·01).
Conclusions Both doses of folic acid reduced homocysteine, but the effects of the 2·0mg dose were about one third greater than the 0·2mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.
Key Words: Homocysteine, folic acid, coronary heart disease, randomized trial
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