In Reply: We agree with Dr Ntaios and colleagues that null results from published randomized trials of folic acid and B vitamins do not rule out the possibility that long-term dietary folic acid fortification may have a beneficial effect on cardiovascular risk. However, dietary fortification has been broadly implemented in a nonrandomized fashion. It will therefore be difficult to disentangle the specific effects of fortification from other changes and improvements in risk factor profiles and preventive therapies that may also have taken place in these populations over the same time period and that may influence cardiovascular risk.
Albert CM, Cook NR, Manson JE. Effect of Folic Acid and B Vitamins on Cardiovascular Disease in Women—Reply. JAMA. 2008;300(12):1409-1410. doi:10.1001/jama.300.12.1410-b