Folate is a water soluble B vitamin, deficiency of which appears to play an important pathogenetic role in the development of anaemia, atherosclerosis, neural tube defects (NTDs), adverse pregnancy outcomes, neuropsychiatric disorders, and cancer.¹ Folic acid is the fully oxidised monoglutamyl form of this vitamin that is used commercially in supplements and in fortified foods. Folate is generally regarded as safe and has long been presumed to be purely beneficial and an ideal functional food component for disease prevention.^2,3 For example, an overwhelming body of evidence for a protective effect of periconceptional folic acid supplementation against NTDs led to mandatory folic acid fortification in the USA and Canada in 1998.⁴ The effectiveness of folic acid fortification in improving folate status has already been shown to be quite striking, with a dramatic increase in blood measurements of folate concentrations in the USA and Canada.⁴ Preliminary reports also suggest a significant reduction (∼15–50%) in the incidence of NTDs in the USA and Canada.⁴

Perhaps one of the most speculative and provocative new medical applications of folate nutrition is the potential role of folate as a cancer preventive agent.^1,5 The concept that folate deficiency enhances, whereas folate supplementation reduces, the risk of neoplastic transformation appears counterintuitive and contradictory to our conventional understanding of folate biochemistry. Folate is an essential cofactor for the de novo biosynthesis of purines and thymidylate, and in this role folate plays an important role in DNA synthesis and replication.^5,6 Consequently, folate deficiency in tissues with rapidly replicating cells results in ineffective DNA synthesis. In neoplastic cells where …