Folate, cancer risk, and the Greek god, Proteus: a tale of two chameleons

Abstract

Evidence indicates that an abundant intake of foodstuffs rich in folate conveys protection against the development of colorectal cancer, and perhaps some other common cancers as well. The issue is complex, however, since some observations in animal and human studies demonstrate that an overly abundant intake of folate among those who harbor existing foci of neoplasia might instead produce a paradoxical promotion of tumorigenesis. The pharmaceutical form of the vitamin, folic acid, might affect the process in a manner that is distinct from natural forms of the vitamin, although this remains a speculative concept. Our limited understanding of this complex relationship is impeding efforts to move ahead with widespread folic acid fortification, but this delay may be necessary to ensure that such programs are instituted in a safe manner.

Figure 1. 1-carbon metabolism in cytosol of most mammalian cells, emphasizing inter-conversion of different forms of folate (simplified)

DHF, Dihydrofolate; dmg, dimethylglycine; S-AdoHcyst, S-adenosylhomocysteine; SAdoMet, S-adenosylmethionine; THF, tetrahydrofolate; 1, methionine synthase; 2, betaine:homocysteine methyltransferase; 3, methylenetetrahydrofolate reductase; 4, serine hydroxymethyltransferase; 5, cystathionine β-synthase