title: Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans.
abstract: Elevated plasma homocysteine concentration is an independent risk factor for vascular disease in humans. In addition to nutritional and genetic factors, an interruption of the coordinate regulatory function of S-adenosylmethionine has been proposed to be involved in the occurrence of hyperhomocysteinemia. The effect of oral S-adenosylmethionine on homocysteine metabolism in humans is unknown. We investigated the effect of oral S-adenosylmethionine (400 mg) on plasma levels of 5-methyltetrahydrofolate, which is the active form of folate in the remethylation of homocysteine to methionine, S-adenosylhomocysteine, the demethylated product of S-adenosylmethionine, homocysteine and methionine over 24 hr in 14 healthy subjects. After oral administration, S-adenosylmethionine increased from 38.0 +/- 13.4 to 361.8 +/- 66.4 nmol/liter (mean +/- S.E., P < .001) and returned to base-line values with a half-life of 1.7 +/- 0.3 hr. Both S-adenosylhomocysteine and 5-methyltetrahydrofolate showed a significant transient increase (from 29.9 +/- 3.7 to 51.7 +/- 7.1 nmol/liter, and from 25.1 +/- 2.5 to 36.2 +/- 3.5 nmol/liter, respectively, P < .001), although homocysteine and methionine did not change over the time of measurement. These changes were not found in subjects without previous S-adenosylmethionine administration. The observed metabolic changes suggest that S-adenosylmethionine, at least in concentrations obtained in this study, does not inhibit 5,10-methylenetetrahydrofolate reductase, the 5-methyltetrahydrofolate forming enzyme. Rather they indicate a positive effect on 5-methyltetrahydrofolate, a key cofactor in homocysteine metabolism, which should be considered in homocysteine lowering strategies for the prevention of vascular disease.
authors.affiliation: University Children's Hospital Basel, Metabolic Unit, Switzerland.
authors.forename: F M
authors.initials: FM
authors.lastname: Loehrer
authors.forename: R
authors.initials: R
authors.lastname: Schwab
authors.forename: C P
authors.initials: CP
authors.lastname: Angst
authors.forename: W E
authors.initials: WE
authors.lastname: Haefeli
authors.forename: B
authors.initials: B
authors.lastname: Fowler
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000284:Administration, Oral; D000328:Adult; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood*; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012016:Reference Values; D012435:S-Adenosylhomocysteine / Q000097:blood*; D012436:S-Adenosylmethionine / Q000008:administration & dosage / Q000494:pharmacology*; D013763:Tetrahydrofolates / Q000097:blood*
chemical_list: D013763:Tetrahydrofolates; D006710:Homocysteine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate