Unraveling the complex relationship between folate and cancer risk

Epidemiologic evidence generally 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. Preclinical models substantiate that the relationship is a genuinely causal one. However, the issue is rather complex because 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. We should not allow the complex nature of this relationship to compel us to ignore it, as understanding its true nature will greatly facilitate our ability to construct intelligent, effective, and safe strategies for the prevention of birth defects and cancer.