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EDITORIAL: Folate and cancer prevention: a closer look at a complex picture [American Journal of Clinical Nutrition]
One should be cautious about drawing strong support from the study by Ericson et al for increasing folate intakes in the general population as part of public health measures. Fortification of grain products has been mandated in several countries for the prevention of neural tube defects. The success of this policy is indisputable, given the significant decreases in neural tube defects in the United States, Canada, and Chile since the initiation of fortification (13). Folate status in the US population has increased substantially; ~40% of the US population has postfortification serum folate concentrations >40 nmol/L—a concentration that has been described as being supraphysiologic (14). At the same time, unmetabolized folic acid is detectable in the circulation of healthy individuals, with unknown physiologic consequences (4). Several European countries are currently considering the introduction of folic acid fortification for the prevention of neural tube defects, perhaps under the assumption that folic acid fortification will also aid in the prevention of cancer and of cardiovascular disease. Yet, as discussed above, there is now increasing evidence from randomized trials that high doses of folic acid can foster the growth of common precancerous lesions. The benefit of reducing a relatively small number of neural tube defects may be outweighed by the possible negative effects on tumor promotion in a substantial fraction of the population. We currently lack good quantitative information on the effects of folic acid on the growth of preneoplastic lesions or on carcinogenic progression. However, even if the extent of these adverse effects was modest, a large number of individuals with cancer precursors would be affected. Thus, a cautionary approach is warranted as we consider whether to recommend an increase in folate status for all.
Folate may play a dual role in cancer development: it may provide protection early in carcinogenesis and in individuals with a low folate status, yet it may promote carcinogenesis if administered later and potentially at very high intakes. We need to evaluate this information carefully when developing public health recommendations and should be mindful that more folate is not better in all circumstances.
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