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Original Research Communication |
1 From the Wageningen Centre for Food Sciences, Wageningen, Netherlands (FVAvO, AM-B, IAB, MBK, and PV); the Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, Netherlands (FVAvO, AM-B, IAB, CEW, MBK, and PV); the Department of Gastroenterology, University Medical Centre Nijmegen, Nijmegen, Netherlands (CEW); and the Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, United Kingdom (RC).
Background: Elevated homocysteine concentrations, a likely risk factor for cardiovascular disease, can be lowered effectively with folic acid. The minimum dose of folic acid required for maximal reduction of homocysteine concentrations is not yet known reliably.
Objective: We aimed to determine the lowest folic acid dose that decreases plasma homocysteine concentrations adequately in healthy older adults.
Design: A dose-response trial with a randomized, double-blind, parallel-group, placebo-controlled design was carried out among 316 Dutch men and women aged 50–75 y. Subjects received daily for 12 wk either a placebo or 1 of the 6 following folic acid doses: 50, 100, 200, 400, 600, or 800 µg. The relative changes in plasma homocysteine concentration in response to increasing doses of folic acid were used to calculate the dose-response curve. An adequate dose of folic acid was defined as the dose that induced 
90% of the maximal reduction in homocysteine concentration.
Results: The relative decrease in plasma homocysteine concentration was associated exponentially with increasing doses of folic acid. From the dose-response curve, the adequate daily dose of folic acid was estimated to be 392 µg, which decreased plasma homocysteine concentrations 22%.
Conclusion: In older adults, daily supplementation with folic acid effectively lowers plasma homocysteine concentrations, and a daily dose of 
400 µg is the minimum dose required for adequate homocysteine reduction.
Key Words: Folic acid • homocysteine • dose response • food fortification • dose-response curve • adult population
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