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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Folic acid fortification of the food supply. Potential benefits and risks for the elderly population.

OBJECTIVE: To estimate the potential benefits and risks of food folic acid fortification for an elderly population. Benefits are expected through the improvement of folate and homocysteine status, but there is also a risk of masking or precipitating clinical manifestations related to vitamin B12 deficiency with increasing exposure to folic acid. DESIGN: Cross-sectional analysis, with projected change at various levels of folic acid fortification. SETTING: Participants in the Framingham Heart Study original cohort. PARTICIPANTS: A total of 747 subjects aged 67 to 96 years who both completed usable food frequency questionnaires and had blood concentrations of B vitamins and homocysteine measured. MAIN OUTCOME MEASURES: Projected blood folate and homocysteine concentrations and combined high folate intake and low plasma vitamin B12 concentration. RESULTS: Percentages of this elderly population with folate intake below 400 microg/d are projected to drop from 66% at baseline to 49% with 140 microg of folate per 100 g of cereal-grain product, to 32% with 280 microg, to 26% with 350 microg, and to 11% with 700 microg. Percentages with elevated homocysteine concentrations (>14 micromol/L) are projected to drop from 26% at baseline to 21% with 140 microg of folate per 100 g, to 17% with 280 microg, to 16% with 350 microg, and to 12% with 700 microg. Without fortification, the prevalence of combined high folate intake (>1000 microg/d) and low plasma vitamin B12 concentration (<185 pmol/L [<250 pg/mL]) was 0.1%. This is projected to increase to 0.4% with folate fortification levels of 140 to 350 microg/100 g and to 3.4% with 700 microg. CONCLUSION: The evidence suggests that, at the level of 140 microg/100 g of cereal-grain product mandated by the Food and Drug Administration, the benefits of folate fortification, through projected decreases in homocysteine level and heart disease risk, greatly outweigh the expected risks. However, quantification of the actual risks associated with vitamin B12 deficiency remains elusive. Before higher levels of folic acid fortification are implemented, further research is needed to better understand the clinical course of various forms of vitamin B12 deficiency, to measure the potential effect of high folate intake on this course, and to identify cost-effective approaches to the identification and treatment of all forms of vitamin B12 deficiency.[1]


  1. Folic acid fortification of the food supply. Potential benefits and risks for the elderly population. Tucker, K.L., Mahnken, B., Wilson, P.W., Jacques, P., Selhub, J. JAMA (1996) [Pubmed]
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