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Potential Benefits and Risks for the Elderly Population

Katherine L. Tucker, PhD; Brenda Mahnken, MSc; Peter W. F. Wilson, MD; Paul Jacques, ScD; Jacob Selhub, PhD

JAMA. 1996;276(23):1879-1885.

Abstract
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.

Desing.
—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 µg/d are projected to drop from 66% at baseline to 49% with 140 µg of folate per 100 g of cereal-grain product, to 32% with 280 µg, to 26% with 350 µg, and to 11% with 700 µg. Percentages with elevated homocysteine concentrations (>14 µmol/ L) are projected to drop from 26% at baseline to 21% with 140 µg of folate per 100 g, to 17% with 280 µg, to 16% with 350 µg, and to 12% with 700 µg. Without fortification, the prevalence of combined high folate intake (>1000 µg/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 µg/100 g and to 3.4% with 700 µg.

Conclusion.
—The evidence suggests that, at the level of 140 µg/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.

Author Affiliations
From the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (Drs Tucker, Jacques, and Selhub and Ms Mahnken), and the Framingham (Mass) Heart Study, National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Wilson).

Footnotes
The contents of this article do not necessarily reflect the views or policies of the US Department of Agriculture or the National Heart, Lung, and Blood Institute.

Reprints: Katherine L. Tucker, PhD, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111.

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