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.