Increased total plasma homocysteine concentration is an independent risk factor for premature atherosclerosis. Elevated levels of homocysteine may reflect low levels of folate, decreased vitamin B₁₂ or vitamin B₆ levels, or inherited abnormalities of certain essential enzymes. Folic acid in dosages of 1 to 10 mg can lower homocysteine levels. Lobo and associates studied a combination of daily low-dose folic acid supplement combined with vitamins B₁₂ and B₆ to reduce homocysteine levels in patients with coronary artery disease.

Ninety-five patients with coronary artery disease were nonrandomly assigned to one of four groups: placebo, 400 μg of folic acid, 1 mg of folic acid or 5 mg of folic acid daily. Patients receiving supplemental folic acid also received additional vitamin B₆ (12.5 mg) and vitamin B₁₂ (500 μg) daily. Treatment was administered for 90 days. Homocysteine, folate, vitamin B₁₂ and vitamin B₆ levels were determined before enrollment in the study and at 30 or 90 days after initiation of therapy.

Baseline demographic variables were similar in all of the groups. After 30 days of therapy, homocysteine levels were significantly lower in the 1- and 5-mg groups. After 90 days of therapy, homocysteine concentrations were significantly lower in all of the treatment groups. There was no significant change in the placebo group. Seven patients reported adverse reactions—one patient in the placebo group, four patients who were taking 400 μg of folate, one taking 1 mg of folate and one taking 5 mg of folate.

The authors conclude that a daily dose of 400 μg of folic acid (a dose commonly available in nonprescription vitamins) combined with vitamins B₁₂ and B₆ normalized homocysteine levels in patients with coronary artery disease. This effect may prevent vascular disease progression.