The commentary piece, published in the Journal of the American Medical Association (JAMA) argues that vitamin therapy – once widely used to lower homocysteine levels – should still play a role in the prevention of stoke, despite recent evidence to suggest that such therapy is ineffective.
In their commentary, Dr. David Spence of the University of Western Ontario and Dr. Meir Stampfer of the Harvard School of Public Health in argue that two key issues have been overlooked in the interpretation of recent clinical trials: the key role of vitamin B12, and the newly recognized role of renal failure.
"It is now clear that the large trials showing no benefit of vitamin therapy obscured the benefit of vitamin therapy because they lumped together patients with renal failure and those with good renal function,” said Spence.
“The vitamins are harmful in renal failure, and beneficial in patients with good renal function, and they cancel each other out," he explained.
Spence also argued that most of the trials did not use a high enough dose of vitamin B12, adding that the commentary provides insights that overturn the widespread belief that "homocysteine is dead."
High levels of the amino acid homocysteine in the bloodstream have been linked to increased risk of stroke and heart attack. It has been believed that therapy with B vitamins could lower homocystine levels, so reducing its effects on blood vessel walls (endothelium).
Several recently published randomised trials and a meta-analysis, have indicated that lowering homocysteine levels with B vitamins had no cardiovascular benefit. Since these results, the authors noted that the use of vitamin therapy to lower homocysteine levels has been “widely regarded as ineffective.”
However, Spence and Stampfer said that many of these studies failed to take subgroup analysis into account:
“It seems that benefit or harm from vitamin therapy used to lower homocysteine levels depends not only on adequate dosing and absorption of vitamin B12 but also on renal function,” said the authors.
They argued that when subgroup analyses are biologically based, thoughtfully developed, and pre-planned – “consideration of their results can enrich the findings from randomised trials and may lead to insights that can help explain apparently divergent results.”
In clinical practice, they said that it may be reasonable to consider acting on such insights.
Volume 306, Issue 23, Pages 2610-2611, doi: 10.1001/jama.2011.1834
“Understanding the Complexity of Homocysteine Lowering With Vitamins: The Potential Role of Subgroup Analyses”
Authors: J.D. Spence, M.J. Stampfe