Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C-->T polymorphism of methylenetetrahydrofolate reductase.
BACKGROUND
The 677C-->T polymorphism of methylenetetrahydrofolate reductase can lead to increased homocysteine. Moderate increases of homocysteine can be lowered by folic acid (0.4-10 mg day-1). This study compared the effect of folic acid with 5-methyltetrahydrofolate, the active form of folate generated by this reductase, on homocysteine levels in healthy subjects and whether this is influenced by the 677C-->T polymorphism.


METHODS
Either 400 micrograms day-1 of [6RS] 5-methyltetrahydrofolate or 400 micrograms day-1 of folic acid were administered orally to 10 wild-type and 10 homozygous subjects. Total homocysteine and folate were determined before and after 3 and 7 weeks of treatment, and 24 weeks after stopping treatment.


RESULTS
After 3 and 7 weeks of treatment with 5-methyltetrahydrofolate, homocysteine levels fell from 11.6 +/- 1.5 to 9.0 +/- 2.3 and 8.7 +/- 1.8 (P < 0.005) in wild-type subjects and from 16.9 +/- 6.8 to 12.3 +/- 4.3 and 11.6 +/- 4.4 mumol/L, mean +/- SD (P < 0.005) in homozygous subjects, proving biological availability of 5-methyltetrahydrofolate irrespective of the 677C-->T genotype. After folic acid for 3 and 7 weeks, values fell from 12.6 +/- 3.3 to 9.2 +/- 2.9 and 9.2 +/- 2.7 (P < 0.005) and from 15.6 +/- 4.9 to 11.7 +/- 3.9 and 9.1 +/- 2.4 mumol L-1, mean +/- SD (P < 0.005) in wild-type and homozygous subjects, respectively. Six months after stopping treatment, homocysteine levels remained lower than pretreatment levels, with statistical significance, only in homozygous subjects treated with 5-methyltetrahydrofolate (12.1 +/- 2.5 vs. 16.9 +/- 6.8, P < 0.01).


CONCLUSIONS
5-methyltetrahydrofolate showed comparable efficacy in reducing homocysteine as folic acid. A prolonged effect 6 months after ceasing treatment with 5-methyltetrahydrofolate in homozygous subjects represents a further phenotypic effect of the 677TT methylenetetrahydrofolate reductase genotype.
Litynski
P
P
University Children's Hospital, Basel, Switzerland.
Loehrer
F
F
Linder
L
L
Todesco
L
L
Fowler
B
B
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018709:Statistics, Nonparametric; D013763:Tetrahydrofolates / Q000627:therapeutic use*; D013997:Time Factors
D013763:Tetrahydrofolates; D005492:Folic Acid; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); C005984:5-methyltetrahydrofolate