In Reply: In response to Drs Mason and Baron, it has been suggested that an increase in colorectal cancer incidence in the late 1990s was linked to the introduction of folic acid fortification in the United States in the mid 1990s.1 If that were the case, this adverse effect would have been expected to emerge within a few years in randomized trials of folic acid supplementation. The most prolonged of the randomized trials in patients with colorectal polyps did report a possible hazard, but it was based on only 58 vs 34 incident cancers at all sites during a mean treatment period of 7.7 years.2 By contrast, despite there being more than 1300 incident cancers in the SEARCH trial (and using a folic acid dose almost 10 times greater than is typically achieved with folate fortification), no significant cancer excess was observed either overall (678 folate vs 639 placebo; RR, 1.07; 95% CI, 0.96-1.19) or at any particular site during a mean treatment period of 6.7 years.
Armitage J, Clarke R, Collins R. Effects of Folic Acid Plus Vitamin B12 vs Placebo in Myocardial Infarction Survivors—Reply. JAMA. 2010;304(16):1783-1784. doi:10.1001/jama.2010.1474