Reducing levels of the amino acid homocysteine through vitamin therapy still has a role to play in reducing stroke, researchers argue.
In a commentary piece published in the Journal of the American Medical Association (JAMA) researchers argue that vitamin therapy, once widely used to lower homocysteine levels, should still play a role in the prevention of stroke, despite recent reports suggesting that such therapy is ineffective.
In the commentary, Dr. David Spence of the University of Western Ontario and Dr. Meir Stampfer of the Harvard School of Public Health argue that two key issues have been overlooked in the interpretation of recent clinical trials: the key role of vitamin B-12 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 B-12, 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 homocysteine levels, reducing its effects on blood vessel walls (endothelium).
Several recently published randomized 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 B-12 but also on renal function," the authors said.
They argued that when subgroup analyses are biologically based, thoughtfully developed and pre-planned, "consideration of their results can enrich the findings from randomized trials and may lead to insights that can help explain apparently divergent results."
Journal of the American Medical Association 306(23):2610-2611, 2011