Don’t reject potential of vitamins to cut heart disease risk because of ‘inappropriate’ clinical trials: Review
A new review in the PubMed-listed journal Cardiovascular Therapeutics found that many of the clinical trials examining if supplementation with B vitamins or vitamin E could benefit cardiovascular and cerebrovascular health neglected to consider confounding factors, such as the use of medication.
This led to a bias and inappropriate conclusions, state Balazs Debreceni from the University of Pecs in Hungary and Laszlo Debreceni from the Heart Disease Research Foundation in Brooklyn, New York.
“From the large vitamin trials, no conclusions along the lines of ‘B vitamin supplements cannot currently be recommended for the prevention of CVD events’ or ‘vitamin E was associated with an increased risk of hemorrhagic stroke’ can be drawn because the results were determined from inappropriate trial settings, and—in the latter case—can be accounted for by the combined action of vitamin E plus aspirin, since antiplatelet and anticoagulant effects are accumulative when taken in combination,” wrote Debreceni and Debreceni.
“We take the view that (1) the B- and E-vitamin prevention therapy can work in the primary prevention, and (2) the large vitamin trials did not have power to settle the debate on the effectiveness of vitamin substitution in the secondary prevention of the cardiovascular diseases.”
Controversy
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.
Epidemiological studies 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.
However, clinical trials including participants at risk of, or already suffering from, cardiovascular disease have produced null results, with some experts arguing that short term B vitamin supplementation should not be expected to reverse the long-term development of heart disease.
In 2009 a prestigious Cochrane review concluded in that supplements of B6, B12 or folate do not affect cardiovascular health, despite lowering homocysteine levels. The review included data from eight randomized controlled trials equivalent to 24,210 participants.
New review
Debreceni and Debreceni analyzed eight B vitamin and four E vitamin trials and found that “possible factors implicated in the failure of vitamin therapies included inappropriate designs.
“The protocols neglected an essential fact: that the impact of some confounding factors, such as concomitant use of statins, acetylsalicylic acid, folic acid, and other drugs, might have led to bias and an inappropriate interpretation of the data.”
“The cardiovascular protective and preventive effects of statins and aspirin might have reduced or abolished the possibility of observing a difference in the number of events between the vitamin and placebo groups for the clinical endpoints.
“We concluded that the vitamin preventive effect on cardiovascular disease may not be rejected in reference to the negative trial evidence.”
Other perspective
Another interpretation of the null findings from clinical trials has been proposed by several different sources, is related to the use of nutrients in diseased populations to try to reverse a lifetime of poor lifestyle.
Criticism has also focused on the design of the trials – some commentators have stated that a set dose of a nutrient for a select period, is an inappropriate way to evaluate the potential of nutrients to influence health and wellness.
Source: Cardiovascular Therapeutics
August 2012, Volume 30, Issue 4, pages 227–233, doi: 10.1111/j.1755-5922.2011.00266.x
“Why Do Homocysteine-Lowering B Vitamin and Antioxidant E Vitamin Supplementations Appear To Be Ineffective in the Prevention of Cardiovascular Diseases?”
Authors: B. Debreceni, L. Debreceni
