5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women.
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 (FADH(2)) (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.


METHODS
In this randomized, placebo-controlled, double-blind study, 160 women received 400 microg FA, the equimolar amount of MTHF (480 microg, 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 > or = 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.
Fohr
Iris P
IP
Department of Pathophysiology of Human Nutrition, Institute of Nutritional Science, University of Bonn, Germany.
Prinz-Langenohl
Reinhild
R
Brönstrup
Anja
A
Bohlmann
Anja M
AM
Nau
Heinz
H
Berthold
Heiner K
HK
Pietrzik
Klaus
K
D000328:Adult; D000704:Analysis of Variance; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy*; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D013763:Tetrahydrofolates / Q000627:therapeutic use*
D013763:Tetrahydrofolates; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate