Folate

1. Folate is a generic descriptor for a water-soluble B-complex vitamin that functions in one-carbon transfer reactions and exists in multiple chemical forms. Most naturally occurring folates are poly-glutamated forms, which enable their retention in the cell. However, folic acid is the most oxidized and stable form of folate, rarely found in food, yet used commonly in vitamin supplements and fortified foods. 2. The nutrient folate is a B vitamin that provides methyl groups for one-carbon transfer reactions, including those supporting the synthesis of nucleotides and methylation reactions. A higher folate status has been consistently associated with decreased cancers risks of the colorectum, esophagus, and possibly pancreas. A decreased breast cancer risk with higher folate intakes among alcohol consumers has also been suggested. 3. Folate is also important for the synthesis of S-adenosylmethionine (SAM), the universal donor of methyl groups necessary for DNA methylation. Together with changes in the histone code, DNA methylation is an important epigenetic mode of gene silencing. 4. Recently, two trials involving the prevention of recurring colorectal polyps have proven that folic acid and aspirin administration did not prevent the recurrence of colorectal adenomas. Conversely, animal studies have proven an inverse relationship between folate deficiency and increased colorectal cancer. The unexpected results of the human prevention trials were interpreted in light of the accumulating evidence from the animal studies. 5. Results from a simulation investigating a dual role of folate in carcinogens conducted by Luebeck et al. indicate that the effects of folate on colon carcinogenesis are age- and dose-dependent, with predominantly increased risk if the amount of folate given were to increase cellular replication rates by 20%. However, a lack of quantitative estimates of the response of tissues or cancer precursors to folate or folic acid supplementation limits this modeling.