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BMJ. 2007 September 22; 335(7620): 587.
PMCID: PMC1988969
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Supplements to lower homocysteine concentration disappoint again

Epidemiological and genetic studies show a clear association between high serum concentrations of homocysteine and a higher risk of cardiovascular disease. So for more than a decade, researchers have been trying to reduce the risk of cardiovascular disease by giving people homocysteine lowering supplements of B vitamins and folic acidacid.. Four large trials have already reported disappointing results. Now a fifth finds that B vitamins and folic acid don't prevent cardiovascular disease, even in high risk patients with chronic renal failure. Once again, the supplements brought down participant's homocysteine concentrations but not their risk of death (hazard ratio 1.04, 95% CI 0.91 to 1.18), heart attack (0.86, 0.67 to 1.08), stroke (0.90, 0.58 to 1.40), or amputation (1.14, 0.79 to 1.64).

figure scut2209.f4

No one can explain why the supplements don't work in large trials, although one explanation is the attenuating effect of fortifying cereals with folic acid. Most of the trials have been done in the US, where fortification is compulsory. Further trials are still under way and when finished will bring the total number of analysable participants to about 52 000. That should be enough to detect even a small effect, says an editorial (p 1212). Unless, of course, there isn't one.


  • JAMA 2007;298:1163-70 [PubMed]

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