title: Effect of homocysteine lowering by 5-methyltetrahydrofolate on redox status in hyperhomocysteinemia.
abstract: The endothelial dysfunction induced by hyperhomocysteinemia can be reversed by 5-methyltetrahydrofolate (5-MTHF) via homocysteine (Hcy) lowering. An additive antioxidant action of 5-MTHF has been suggested to ameliorate endothelial dysfunction through increased nitric oxide production and superoxide radical scavenging, independent of Hcy lowering. The aim of the study was to assess whether 5-MTHF affects the redox state in hyperhomocysteinemia. We examined the effect of 3 months of oral 5-MTHF treatment (15 mg/day) on the redox pattern in 48 hyperhomocysteinemic subjects compared to 24 untreated hyperhomocysteinemic subjects. By analysis of variance with repeated measures in the 72 subjects, 5-MTHF markedly decreased plasma total Hcy (p-tHcy; P = 0.0001) and blood-total glutathione (GSH; b-tGSH; P = 0.002). By multivariate linear regression in the treated subjects, p-tHcy changes from baseline to 3 months (adjusted by baseline p-tHcy levels) correlated only with changes in reduced cysteinylglycine (P = 0.001). The effects of treatment on Hcy lowering and GSH metabolism were greater in medium than in moderate hyperhomocysteinemia. In conclusion, high-dose 5-MTHF treatment for 3 months ensures marked Hcy lowering to normal values even in subjects with high Hcy levels, and should be the treatment of choice in medium hyperhomocysteinemia. Furthermore, 5-MTHF shows a favorable interaction with GSH metabolism.
authors: CNR Clinical Physiology Institute, Niguarda Cà Granda Hospital, Milan, Italy.
authors: Raffaele
authors: R
authors: Caruso
authors: Jonica
authors: J
authors: Campolo
authors: Valentina
authors: V
authors: Sedda
authors: Benedetta
authors: B
authors: De Chiara
authors: Cinzia
authors: C
authors: Dellanoce
authors: Francesco
authors: F
authors: Baudo
authors: Annamaria
authors: A
authors: Tonini
authors: Marina
authors: M
authors: Parolini
authors: Giuliana
authors: G
authors: Cighetti
authors: Oberdan
authors: O
authors: Parodi