Reduction of Plasma Homocyst(e)ine Levels by Breakfast Cereal Fortified with Folic Acid in Patients with Coronary Heart Disease

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Abstract
The Food and Drug Administration (FDA) has recommended that cereal-grain products be fortified with folic acid to prevent congenital neural-tube defects. Since folic acid supplementation reduces 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 plasma homocyst(e)ine levels. To test this hypothesis, we assessed the effects of breakfast cereals fortified with three levels of folic acid, and also containing the recommended dietary allowances of vitamins B6 and B12, in a randomized, double-blind, placebo-controlled, crossover trial in 75 men and women with coronary artery disease. Plasma folic acid increased and plasma homocyst(e)ine decreased proportionately with the folic acid content of the breakfast cereal. Cereal providing 127 μg of folic acid daily, approximating the increased daily intake that may result from the FDA's enrichment policy, increased plasma folic acid by 30.8 percent (P = 0.045) but decreased plasma homocyst(e)ine by only 3.7 percent (P = 0.24). However, cereals providing 499 and 665 μg of folic acid daily increased plasma folic acid 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. Cereal fortified with folic acid has the potential to increase plasma folic acid levels and reduce plasma homocyst(e)ine levels. Further clinical trials are required to determine whether folic acid fortification may prevent vascular disease. Until then, our results suggest that folic acid fortification at levels higher than that recommended by the FDA may be warranted.