Supplements of folic acid, and vitamins B6 and B12 may not affect cardiovascular health, despite lowering homocysteine levels, says a new study published in the Journal of the American Medical Association.
The potential role of B vitamins in heart health, by reducing levels of the amino acid homocysteine reported to increase the risk of cardiovascular disease, is controversial. The controversy is set to continue, with the new study being focused on women who either had a history of CVD or were considered at high risk of CVD.
The trial of B vitamins in a diseased and high risk population begs questions of the use of nutrients to correct a lifetime of poor nutrition.
"In this large-scale, placebo-controlled, randomized trial among high-risk women participants, we found no overall effects of a combination of folic acid, vitamin B6, and vitamin B12 on the primary outcome of total CVD events over the largest number of person-years and the longest follow-up period reported to our knowledge (7.3 years)," wrote lead author Christine Albert from Brigham and Women's Hospital and Harvard Medical School.
The WAFACS conclusions are based on results from a randomized, placebo-controlled study of folic acid and other B vitamins in a subset of 5,442 women taking part in a larger trial called Women's Antioxidant Cardiovascular Study (WACS).
Participants were health professionals over age 40 who either had a history of CVD or were considered at high risk due to three or more CVD risk factors such as high blood pressure, high cholesterol levels, diabetes and smoking
The results, originally presented at the American Heart Association's Scientific Sessions 2006, go against epidemiological studies that have linked increased blood levels of the amino acid homocysteine to an increased risk of cardiovascular disease (CVD). It has been suggested that by lowering the levels of homocysteine in the blood with B-vitamins, people could cut the risk of CVD.
Albert and co-workers randomly assigned women to receive daily supplements containing folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) or a matching placebo. Such doses exceed the US recommended daily allowance (RDA) of 400 micrograms of folic acid, 2 mg of vitamin B6, and 6 micrograms of vitamin B12.
After seven years of follow-up, the researchers had documented 796 participants with a confirmed CVD event, such as a heart attack, stroke, coronary revascularization, or CVD death. No significant difference in these events was observed between the groups, despite an 18.5 per cent decrease in homocysteine levels being observed in the B vitamin group.
"Our results are consistent with prior randomized trials performed primarily among men with established vascular disease and do not support the use of folic acid and B vitamin supplements as preventive interventions for CVD in these high-risk fortified populations," wrote the authors.
Explaining the disagreement
In an accompanying editorial, Eva Lonn from McMaster University in Ontario, said that previous promising results from epidemiological studies led to "overzealous interpretations" and "unjustified early enthusiasm".
In attempting to explain differences from epidemiological studies and clinical trials, Lonn suggested possible reasons to include: "Overestimation of a possible treatment effect based on earlier epidemiological studies resulting in underpowered trials; the introduction of mandatory folate-food-fortification policies in the United States and Canada resulting in lesser effects of B vitamin supplements on homocysteine levels; the vitamin doses used; and potential unexpected proatherosclerotic effects of folic acid supplementation, which may have counteracted benefits associated with homocysteine lowering.
"However, it is possible that the treatment truly has no effect on vascular risk," she added.
A number of large trials are still ongoing, said Lonn, and that it was critically important to complete these trials in order to answer the outstanding questions.
"However, until further data become available it is essential to remain firmly grounded on the available evidence and to admit that once again experimental and
observational data do not always translate into therapeutic benefits," wrote Lonn.
Volume 299, Issue 17, Pages 2027-2036
"Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease: A Randomized Trial"
Authors: C.M. Albert, N.R. Cook, J.M. Gaziano, E. Zaharris, J. MacFadyen, E. Danielson, J.E. Buring, J.E. Manson
Volume 299, Issue 17, Pages 2086-2087
"Homocysteine-Lowering B Vitamin Therapy in Cardiovascular Prevention - Wrong Again?"
Authors: E. Lonn