Effects of Folic Acid Plus Vitamin B₁₂ vs Placebo in Myocardial Infarction Survivors

To the Editor: Past observations have raised a concern that habitual intake of supraphysiological doses of folic acid might enhance the risk of cancer among persons with precancerous or cancerous lesions. Cancers of the colorectum and prostate have been particularly implicated. Although the primary purpose of the SEARCH trial¹ was to examine whether folic acid and vitamin B₁₂ supplementation would diminish cardiovascular events over 6 to 7 years of follow-up, information on incident cancers was collected as a secondary end point. A relative increase of 7% in overall cancer risk occurred with the intervention (rate ratio [RR], 1.07; 95% confidence interval [CI], 0.96-1.19); for colorectal cancer, the RR was 0.95 (95% CI, 0.71-1.27) and for prostate cancer, 1.18 (95% CI, 0.94-1.49). The authors concluded that the results “ . . . indicate that folic acid supplementation has no significant adverse effects on cancer. . . . ” We believe that the data in this study do not justify that conclusion.