Folic acid elicits diverse effects over all major life stages and body systems

Over several decades, the vitamin supplement folic acid has been praised for its ability to reduce neural tube defects in the developing embryo. Many studies show that folic acid plays a vital role in the reduction of severe and diverse congenital abnormalities. The health benefits of folic acid are so highly regarded that in the mid-1990s Food and Drug Administration mandated that foods be fortified with folic acid, and it is generally accepted that it should be consumed unconditionally as a part of prenatal care. More recent studies however, suggest that supplementation may not be entirely beneficial, and that safety depends on dosage. Inappropriate supplementation of folic acid can influence risk for health implications such as pre-term birth, multiple births, chronic disease development in children, and vascular, neurodegenerative disease, and tumorigenesis in adults. There is a concerning rise in chronic diseases such as obesity, Type II diabetes, cardiovascular disease, and cancer which might in part be mediated by inappriate exposure to folic acid. Folic acid supplementation may also be a source for epigenetic modifications, leading to transgenerational effects. This review synthesizes the literature, highlighting the positive and negative effects that folic acid has across life stages and body systems. We find that the benefits of folic acid supplementation vary across life stage. For example, exposure during development is generally protective, but there is little evidence that folic acid supplementation is beneficial when taken by healthy children and adults. The benefits of folic acid supplementation also depend on body system. For example, exposure during adulthood likely decreases risk of cardiovascular disease but also might increase risk of colon cancer. A comprehensive understanding of folic acid’s effects across life stage and body systems will facilitate the development of studies to understand mechanisms of action, and allow personalized healthcare and dosing regimens