Folic Acid: Beyond Metabolism

Abstract

Mandatory and discretionary fortification with folic acid is eliminating deficiency of this vitamin. Blood levels of the vitamin have never been higher, with hematologic folate values commonly exceeding the upper range of calibration. The synthetic analog (pteroylmonoglutamic acid) prevents neural tube defects and lowers homocysteine, both positive attributes, yet negative correlates of pteroylmonoglutamic acid are increasingly reported. These involve increased risk for common cancers (ie, colon, breast, prostate) and antimetabolite effects on natural killer cells and at dihydrofolate reductase, a critical gatekeeper enzyme. This review, however, takes a different, human ecological perspective, examining novel folate-related phenomena distinct from the classic metabolic role of the vitamin in maintaining health and well-being. An argument is developed that at molecular, cellular, and organism levels, folate is crucial to some important events that link light to life.