The NORVIT Trial

Abstract & Commentary

By Alan Z. Segal, MD, Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, NewYork-Presbyterian Hospital. Dr. Segal is on the speaker's bureau of Boehringer Ingelheim.

Synopsis: Among patients on folic acid, with or without the addition of B-6, there was a non-significant trend toward an increase in cancer rates.

Source: Bonaa, et al. NORVIT: The Norwegian Vitamin Trial. Randomised Trial of Homocysteine-Lowering with B-Vitamins for Secondary Prevention of Cardiovascular Disease After Acute Myocardial Infarction. Presented at the European Society of Cardiology, 9/5/05, Stockholm, Sweden.

Plasma homocysteine has been shown to be a strong and independent risk factor for vascular disease, such as myocardial infarction and stroke. It is, therefore, common to measure homocysteine levels in stroke patients and treat with folic acid when homocysteine is found to be elevated greater than 10 umol/L. Data from randomized trials to support this practice is limited and, possibly suggests, that it may be deleterious. The Vitamin Intervention for Stroke Prevention (VISP) trial did not show any reduction in stroke or myocardial infarction among stroke patients assigned a regimen of folic acid 2.5mg, vitamin B-6 25mg and vitamin B-12 400µ. The most recent data from Bonaa et al suggest that vitamin supplementation for patients who are post-myocardial infarction are not only ineffective, but may also be dangerous.

Bonna and colleagues performed a randomized, double-blind trial for secondary prevention of vascular events, examining 3749 patients over a period 3.5 years. Study patients had suffered an acute myocardial infarction within the prior 7 days. Study drugs were folic acid 0.8mg per day and vitamin B-6 40 mg per day. All folic acid pills also contained 400µ of vitamin B-12. The trial had a 2x2 factorial design, with patients receiving folic Acid/vitamin B-12, vitamin B-6, both or neither.

After 2 months, plasma homocysteine levels fell by 28% in the patients taking folic acid, whether or not they were also taking vitamin B-6. The primary end point, a composite of MI and stroke, occurred equally in the folic acid, vitamin B-6, and placebo groups but, in the group that received combination folic acid and B-6, there was a significant increase in these events. Compared to placebo control, the folic acid/B-6 group had a relative risk for MI and stroke of 1.2 (P = .03). Among patients on folic acid, with or without the addition of B-6, there was a non-significant trend (with a relative risk risk of 1.4) toward an increase in cancer rates.

Commentary

These data add to a large body of evidence suggesting a lack of efficacy for vitamin supplementation in the prevention of not only vascular events but also cancer. Although as yet unpublished, these data suggest that combination vitamins containing folic acid, and vitamins B-12 and B-6 (marketed as Foltx or Folgard, for example) may contribute to vascular events rather than prevent them. These data strongly contrast with epidemiological data suggesting that dietary intake of these vitamins is highly beneficial. This leads to the advice given to me many years ago by one of my medical school mentors, "There's no substitute for what your mother told you—eat your vegetables!"