Reduction of Plasma Homocyst(e)ine Levels by Breakfast Cereal Fortified with Folic Acid in Patients with Coronary Heart Disease
Manuel R. Malinow, M.D., Paul B. Duell, M.D., David L. Hess, Ph.D., Peter H. Anderson, Ph.D., Warren D. Kruger, M.D., Beverley E. Phillipson, M.D., Robert A. Gluckman, M.D., Peter C. Block, M.D., and Barbara M. Upson, B.S.
Background The Food and Drug Administration (FDA) has recommendedthat cereal-grain products be fortified with folic acid to preventcongenital neural-tube defects. Since folic acid supplementationreduces levels of plasma homocyst(e)ine, or plasma total homocysteine,which are frequently elevated in arterial occlusive disease,we hypothesized that folic acid fortification might reduce plasmahomocyst(e)ine levels.
Methods To test this hypothesis, we assessed the effects ofbreakfast cereals fortified with three levels of folic acid,and also containing the recommended dietary allowances of vitaminsB6 and B12, in a randomized, double-blind, placebo-controlled,crossover trial in 75 men and women with coronary artery disease.
Results Plasma folic acid increased and plasma homocyst(e)inedecreased proportionately with the folic acid content of thebreakfast cereal. Cereal providing 127 µg of folic aciddaily, approximating the increased daily intake that may resultfrom the FDA's enrichment policy, increased plasma folic acidby 30.8 percent (P = 0.045) but decreased plasma homocyst(e)ineby only 3.7 percent (P = 0.24). However, cereals providing 499and 665 µg of folic acid daily increased plasma folicacid by 64.8 percent (P<0.001) and 105.7 percent (P = 0.001),respectively, and decreased plasma homocyst(e)ine by 11.0 percent(P<0.001) and 14.0 percent (P = 0.001), respectively.
Conclusions Cereal fortified with folic acid has the potentialto increase plasma folic acid levels and reduce plasma homocyst(e)inelevels. Further clinical trials are required to determine whetherfolic acid fortification may prevent vascular disease. Untilthen, our results suggest that folic acid fortification at levelshigher than that recommended by the FDA may be warranted.
Source Information
From the Division of Pathobiology and Immunology (M.R.M., P.B.D., B.M.U.) and the Division of Reproductive Sciences (D.L.H.), Oregon Regional Primate Research Center, Beaverton; Department of Medicine, Oregon Health Sciences University (M.R.M., P.B.D., B.E.P., P.C.B.), and Providence St. Vincent Medical Center (M.R.M., P.H.A., B.E.P., R.A.G., P.C.B.) — both in Portland; and the Fox Chase Cancer Center, Philadelphia (W.D.K.).
Address reprint requests to Dr. Malinow at the Oregon Regional Primate Research Center, 505 NW 185th Ave., Beaverton, OR 97006-3448.
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