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Original Research Communication |
1 From the Department of Pathophysiology of Human Nutrition, Institute of Nutritional Science (IPF, RP-L, AB, and KP), and the Institute of Clinical Pharmacology, Medical School (HKB), University of Bonn, Germany, and the Department of Food Toxicology, Center for Food Sciences, School of Veterinary Medicine, University of Hannover, Germany (AMB and HN).
Background: Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease and neural tube defects. The polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (FADH2) (MTHFR) influences the tHcy concentration and the response to tHcy-lowering therapy. Supplementation with folic acid (FA) decreases plasma tHcy, but limited data are available on the effect of 5-methyltetrahydrofolate (MTHF).
Objective: We evaluated the tHcy-lowering potential of low-dose FA and of MTHF with respect to the MTHFR genotype.
Design: In this randomized, placebo-controlled, double-blind study, 160 women received 400 µg FA, the equimolar amount of MTHF (480 µg, racemic mixture), or a placebo daily during an 8-wk treatment period. Blood samples were collected at baseline and at 4 and 8 wk.
Results: Changes in plasma tHcy concentration depended on the supplemented folate derivative and the MTHFR genotype. Supplementation with FA significantly decreased tHcy concentrations by 
13% in women of all 3 genotypes after both 4 and 8 wk. The greatest decrease was 20% (P < 0.05) in the women with the TT genotype after 4 wk. MTHF supplementation also decreased tHcy, but only the women with the CT genotype had a significant decrease after 4 wk (7%; P < 0.05). The largest nonsignificant reduction (15%) occurred in the women with the TT genotype after 4 wk of MTHF supplementation.
Conclusions: The response to tHcy-lowering therapy is influenced by MTHFR genotype. Women with the TT genotype seem to benefit the most from supplementation with either FA or MTHF. In women with the CT or CC genotype, FA is more effective than MTHF in lowering plasma tHcy.
Key Words: MTHFR genotype • homocysteine • folic acid • methyltetrahydrofolate • methylenetetrahydrofolate reductase • supplementation • women
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