The findings appear to close the door on the potential benefit of lowering homocysteine levels with folic acid supplements, according to report author Robert Clarke, of the University of Oxford in the United Kingdom, and his colleagues.
The researchers also said previous studies that suggested high levels of homocysteine might be a modifiable risk factor for heart disease were plagued by publication bias and methodological problems.
Clarke and his team analyzed data on nearly 50,000 heart disease patients and 68,000 healthy people, culled from 86 published studies and 19 unpublished studies. There was no increased risk of heart disease in people who had an MTHFR gene variant that is associated with 20 percent higher blood homocysteine levels.
The MTHFR gene plays a role in the production of methylene tetrahydrofolate reductase, which uses folate to break down and remove homocysteine.
The study appears in this week's issue of the journal PLoS Medicine.
"The discrepancy between the overall results in the unpublished and the published datasets is too extreme to be plausibly dismissed as a chance finding," the researchers wrote. "Some studies, particularly if small, might have been prioritized for publication by investigators, referees or editors according to the positivity of their results and some may have been liable to other methodological problems that bias the average of all results. To avoid such biases, we chiefly emphasize the new results from the previously unpublished datasets."
"The magnitude of the effect of publication bias is substantial and, in addition to distorting the association of MTHFR with [coronary heart disease] in published studies, publication bias may also help explain the discrepant findings recently reported for MTHFR and stroke," they concluded.
More information
The U.S. National Heart Lung and Blood Institute has more about coronary heart disease.
