Grant: Operating Grant

Folate, a B vitamin is generally regarded as safe and has long been presumed to be purely beneficial, and is in fact promoted as the ultimate functional food component for disease prevention. In Canada, an overwhelming body of evidence for a protective effect of periconceptional folic acid supplementation on neural tube defects led to mandatory folic acid fortification in 1998. Also, up to 40% of the Canadian population are taking folic acid supplementation. Over the past decade, the Canadian population has been exposed to a drastic increase in folate intake, for which essentially no data on safety exist. No studies have been done to look directly or even indirectly for the adverse effects of greatly increased folate intakes. Although folate fortification has significantly improved folate status and reduced neural tube defects rates in Canada, the possibility remains that the vast majority of the Canadian population, who are not at risk of neural tube defects but have been unintentionally exposed to high amounts of folic acid, may benefit less and may even experience unexpected, potentially serious adverse effects from an increase in folic acid intake. Indeed, an emerging body of evidence has recently warned of new potential harmful effects of folic acid supplementation. Although health consequences of folate insufficiency and deficiency have been extensively studied, studies examining the adverse effects of folic acid supplementation on health outcomes and underlying mechanisms are lacking. The developing fetus and the aging population might be particularly vulnerable to adverse effects of high levels of folic acid. We propose to conduct animal and mechanistic studies to determine potential adverse effects of folic acid supplementation and associated mechanisms in these vulnerable subgroups.