Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B₆ and B₁₂

An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo- controlled, single-blind, dose-ranging study evaluates the effect of low- dose folic acid on homocysteine levels in 95 patients aged 61 ± 11 years (mean ± SD) with documented CAD. Patients in each group were given either placebo or 1 of 3 daily supplements of folic acid (400 μg, 1 mg, or 5 mg) for 3 months. Each active treatment arm also received 500 μg vitamin B₁₂ and 12.5 mg vitamin B₆. Total plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400 μg reduced homocysteine levels from 13.8 ± 8.8 to 9.6 ± 2.0 μmol/L at 90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 ± 6.4 to 9.8 ± 4.0 μmol/L (p = 0.001) and from 14.8 ± 6.9 to 9.7 ± 3.3 μmol/L (p <0.001), respectively. The decrease was similar in all treatment groups. There was no significant change with placebo. Although the sample size is small, these findings suggest that daily administration of 400 μg/day folic acid combined with vitamin B₁₂ and vitamin B₆ may be equivalent to higher doses in reducing homocysteine levels in patients with CAD.