title: Folic acid effects on s-adenosylmethionine, s-adenosylhomocysteine, and DNA methylation in patients with intermediate hyperhomocysteinemia.
abstract: OBJECTIVE
  Folic acid (FA) supplementation decreases homocysteine (tHcy) levels. However, little is known about the effects of FA treatment on DNA methylation or plasma S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) concentrations. The purpose of this study was to investigate the effects of FA supplementation on AdoMet, AdoHcy, and genomic DNA methylation in hyperhomocysteinemic subjects without end-stage renal disease.
  
  
  METHODS
  To evaluate the effects of 5 mg FA/d for 8 weeks, we recruited 7 hyperhomocysteinemic MTHFR677TT patients (tHcy >30 μmol/L) with normal renal function.
  
  
  RESULTS
  FA supplementation induced a decrease in tHcy (from 51.1 ± 21 at baseline to 26.1 ± 27 μmol/L after folate supplementation; p < 0.01). A parallel increase was seen in plasma AdoMet concentrations and the AdoMet/AdoHcy ratio (p < 0.05). However, FA supplementation had no effect on global DNA methylation levels in the present study.
  
  
  CONCLUSIONS
  Supraphysiologic FA supplementation can modulate biochemical markers in one-carbon metabolism such as tHcy, AdoMet, and the AdoMet/AdoHcy ratio in hyperhomocysteinemic subjects. However, the reduction in homocysteinemia and the increased availability of methyl compounds provided by vitamin supplementation may not be sufficient to affect genomic DNA methylation.
authors.affiliation: Department of Medicine, University of Verona School of Medicine, Verona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pizzolo
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Sang W
authors.initials: SW
authors.lastname: Choi
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Guarini
authors.forename: Nicola
authors.initials: N
authors.lastname: Martinelli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Stanzial
authors.forename: Roberto
authors.initials: R
authors.lastname: Corrocher
authors.forename: Oliviero
authors.initials: O
authors.lastname: Olivieri
authors.forename: Simonetta
authors.initials: S
authors.lastname: Friso
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D012435:S-Adenosylhomocysteine / Q000097:blood*; D012436:S-Adenosylmethionine / Q000097:blood*; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D014803:Vitamin B Complex; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)