Homocysteine lowering with B vitamins again fails to show benefit

September 4, 2007 By Sabina A. Murphy, M.P.H. [mailto:smurphy@perfuse.org]

Vienna, Austria: Adding to a growing body of literature showing no benefit with homocysteine lowering using B vitamins, the Western Norway B-vitamin intervention trial (WENBIT) confirmed no effect of supplementation in patients with suspected coronary artery disease. The study was presented today at the European Society of Cardiology Congress by Dr. Marta Ebbing.

Early observational studies found that patients with high levels of homocysteine were at an increased risk of cardiovascular events, leading to the hypothesis that lowering these levels with B vitamin supplementation could potentially lower cardiovascular events. However, several large-scale randomized trials enrolling more than 12,000 patients to date have shown no impact on clinical events with folic acid and B vitamins, despite these agents effectively lowering homocysteine levels in the studies. These studies include the NORVIT trial conducted in ST elevation MI patients and the HOPE 2 trial conducted in patients with cardiovascular disease or diabetes.

WENBIT randomized patients undergoing cardiac catheterization for suspected coronary artery disease in a 2 x 2 factorial design to folic acid 0.8 mg plus vitamin B12 0.4 mg and vitamin B6 40 mg per day (n = 771); folic acid 0.8 mg plus vitamin B12 0.4 mg per day (n = 769); vitamin B6 40 mg per day (n = 771); or placebo (n = 779). Most of the patients in the trial were found to have stable CAD (84%) and 15% were found to have an acute coronary syndrome.

Baseline homocysteine levels dropped by 28% in the folic acid groups from a mean of 10.8 mmol/L at baseline. The primary endpoint of death, MI, hospitalization for unstable angina, or stroke through a median 38 month follow-up was not altered by the vitamin supplementation, with events occurring in 93 patients in the folic acid + B12 + B6 group, 126 patients in the folic acid + B12 group, 106 patients in the B6 group, and 97 patients in the placebo group. This gave a relative risk of 1.10 when comparing the folic acid + B12 groups with the non folic acid + B12 groups (p = 0.35), and a relative risk of 0.89 when comparing the B6 groups with the non B6 groups (p = 0.23).

While NORVIT found a non-significant increase in cancer with folic acid, WENBIT showed no evidence pointing to a difference in the rate of cancers with folic acid in the 156 patients who developed the disease during the trial.

The presenter of the WENBIT trial, Dr. Marta Ebbing from the Haukeland University Hospital in Bergen, Norway, concluded that "B-vitamin supplementation is not justified as secondary prevention in cardiovascular disease."