This week’s PLoS Medicine reports on a comprehensive study that reveals that levels of the amino acid, homocysteine, have no significant effect on the risk of developing coronary heart disease. This concludes the ongoing argument of the previously suggested benefits of lowering homocysteine with folate acid.
According to earlier studies, high blood levels of homocysteine might be a modifiable risk factor for coronary heart disease. However, Robert Clarke, from the Clinical Trial Service Unit and Epidemiological Studies Unit at the University of Oxford and his team, have proven in a detailed assessment of data from 19 unpublished and 86 published studies that lifelong moderate elevation of homocysteine levels had no important effect on the risk of developing coronary heart disease.
The results of the study indicate that extensive publication bias, combined with methodological problems have previously influenced suggestions to associate homocysteine with coronary heart disease risk.
The researchers’ findings demonstrated that there was no risk of developing coronary heart disease in almost 50,000 people with coronary heart disease and 68,000 controls, with a variant of the MTHFR gene that is linked to a 20% higher blood homocysteine. The MTHFR gene reduces methylene tetrahydofolate, which uses folate to break down and remove homocysteine.
The researchers comment:
“The discrepancy between the overall results in the unpublished and the published datasets is too extreme to be plausibly dismissed as a chance finding. 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 To avoid such biases, we chiefly emphasize the new results from the previously unpublished datasets.”
In the same journal, the authors concluded:
“The magnitude of the effect of publication bias is substantial and in addition to distorting the association of MTHFR with CHD [coronary heart disease] in published studies, publication bias may also help explain the discrepant findings recently reported for MTHFR and stroke.”
Significantly, the results show a consistency between not finding any evidential link of disease with high homocysteine levels in the 50,000 unpublished heart disease cases with the MTHFR genetic variant and the zero results of 10 large trials that tested the effects of 5 years of folic acid therapy in 50,000 participants in terms of its effect on coronary heart disease. Therefore, both the genetic studies and the trials argue against using folic acid supplements in order to reduce the risk of coronary heart disease.
Written by Petra Rattue