Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease.
What this study found
Both folic acid doses reduced plasma homocysteine versus placebo, and the 2.0 mg dose produced a larger reduction than the 0.2 mg dose. At 6 months, homocysteine fell by 1.8 mol/L (95% CI 1.3-2.3; P<0.001) with 2.0 mg and by 1.2 mol/L (95% CI 0.8-1.7; P<0.001) with 0.2 mg. Baseline homocysteine was similar in both active groups at 10.9 mol/L. The authors concluded that higher-dose folic acid gives greater homocysteine lowering, while folic acid fortification could also reduce population homocysteine levels.
- Study & population
- Randomized trial among 723 adults with coronary heart disease, including prior myocardial infarction or unstable angina, recruited from 28 hospitals in Australia and New Zealand.
- Intervention
- Participants in the active arms received folic acid 2.0 mg daily or 0.2 mg daily for 6 months.
- Key limitation
- Follow-up was only 6 months, so the findings apply to a surrogate biomarker rather than clinical cardiovascular events.
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Open PDFOriginal abstract
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 2.0 mg daily, folic acid 0.2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2.0 mg folic acid reduced homo-cysteine by 1.8 micromol x 1(-1) [95% confidence interval (CI) 1.3-2.3] and 0.2 mg reduced homocysteine by 1.2 micromol x 1(-1) [95% CI 0.8-1.7). The higher dose reduced homocysteine significantly more than the lower dose (P=001). CONCLUSIONS Both doses of folic acid reduced homocysteine, but the effects of the 2.0 mg dose were about one third greater than the 0.2 mg 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.