title: Folic acid treatment increases homocysteine remethylation and methionine transmethylation in healthy subjects.
abstract: Folic acid treatment decreases plasma total homocysteine concentrations in healthy subjects, but the effects on homocysteine metabolism are unknown. In the present study, we investigated the effect of 3 weeks of oral treatment with 5 mg of folic acid on one-carbon flux rates in 12 healthy subjects, using in vivo stable isotope methods. In addition, we determined the effect of folic acid on blood concentrations of amino acids which may have regulatory roles in homocysteine metabolism, i.e. homocysteine, AdoMet (S-adenosylmethionine), AdoHcy (S-adenosylhomocysteine), serine and glycine. Primed, continuous infusions with [2H3-methyl-1-13C]methionine were used to determine flux rates of methionine transmethylation, homocysteine remethylation and homocysteine trans-sulphuration. Metabolic homocysteine clearance was defined as the ratio of trans-sulphuration and plasma homocysteine level. Folic acid treatment increased the homocysteine remethylation rate by 59% [95% CI (confidence interval), 13-97%; P = 0.02] and methionine transmethylation rate by 20% (95% CI, 3-41%; P=0.03). Plasma total homocysteine concentration (-18%; 95% CI, -28 to -9%; P<0.01) and the serine/glycine ratio (-20%; 95% CI, -63 to -6%; P<0.01) decreased significantly, and the AdoMet/AdoHcy ratio (11%; 95% CI, 1-20%; P = 0.02) increased significantly. Changes in one-carbon flux rates did not correlate significantly with changes in plasma concentration of these amino acids. In conclusion, folic acid treatment lowered plasma homocysteine concentration and increased whole-body remethylation and transmethylation flux in healthy subjects.
authors.affiliation: Department of Internal Medicine, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Stam
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Coen
authors.initials: C
authors.lastname: van Guldener
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Kees
authors.initials: K
authors.lastname: de Meer
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D008875:Middle Aged; D014815:Vitamins / Q000097:blood
chemical_list: D000596:Amino Acids; D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D008715:Methionine