JAMA 2008 (Aug 20); 300 (7): 795–804
Ebbing M1, Bleie Ø, Ueland PM, Nordrehaug JE, Nilsen DW,
Vollset SE, Refsum H, Pedersen EK, Nygård O.
Department of Heart Disease,
Haukeland University Hospital,
Jonas Liesvei 65, 5021
Editorial Commentary: This study is a classic reminder that closing the barn door, AFTER your horse has escaped, is a fool's errand.
Poorly designed studies like this provide fodder for the press to make rediculous claims like B vitamins cannot prevent heart disease. In fact, it's already well known that low levels of circulating B vitamins are associated with high levels of homocystein (HCY), and that
high levels of HCY are associated with cardiovascular disease.
What were these researchers thinking? Let's give B vitamins to people with ADVANCED heart disease and see what happens. What a waste of time and money. All of the participants in this study were in their mid-60s, and over 78 percent of the subjects were concomitantly taking beta blockers, and over 88 percent were taking statin drugs for their pre-existing heart disease.
The “good news” is that this study confirms that B vitamins does reduce homocystein levels, even in those with advanced vascular disease. The sad conclusion is that vascular damage, caused by long-term exposure to the corrosive effects of homocystein, probably cannot be reversed by last minute supplementation.
Andrew Shao, Ph.D., vice president, scientific and regulatory affairs, Council for Responsible Nutrition (CRN), said the results were not particularly surprising. “Recent similar randomized controlled trials have shown that while B vitamins can lower homocysteine levels, they may not ‘cure’ or reduce the risk of subsequent cardiovascular events in patients who already have cardiovascular disease,” he said. “But this study, like other similarly designed studies, still fails to answer the question of whether B vitamin supplementation, over the long-term, can help reduce the risk of cardiovascular disease in a population that is healthy at baseline. It’s important to remember that there is a large body of observational data that suggests that higher B vitamin intake and lower homocysteine levels are both associated with lower CVD risk, which is consistent with how vitamins are intended to be used—as a preventive measure, rather than as a ‘treatment’ to already existing disease.”
CONTEXT: Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B(12) can lower plasma total homocysteine levels.
OBJECTIVE: To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.
INTERVENTIONS: Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780). MAIN OUTCOME MEASURES: The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.
RESULTS: Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).
CONCLUSIONS: This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with (advanced) coronary artery disease.
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