title: Cyclic supplementation of 5-MTHF is effective for the correction of hyperhomocysteinemia.
abstract: Folic acid supplementation is the mainstay treatment of hyperhomocysteinemia (HHcy). However, no recommendations are currently available in regard to the optimal replacement therapy. Therefore, this prospective study hypothesized that a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 5-methyltetrahydrofolate (5-MTHF) would reduce plasma levels of fasting total homocysteine (tHcy) in patients with mild/moderate HHcy. Patients with a new diagnosis of mild/moderate HHcy were evaluated for the methylenetetrahydrofolate reductase genotype and the presence of major features of metabolic syndrome. All enrolled subjects received a cyclic 5-MTHF oral supplementation and were reevaluated after each treatment cycle for a total of 2 years. In the 246 enrolled subjects, a significant reduction of tHcy levels occurred after the first cycle of treatment (from 31.6 ± 13.6 to 14.4 ± 5.77 μmol/L, P < .001) and during the whole 2-year follow-up (from 31.6 ± 13.6 to 12.18 ± 3.03 μmol/L, P < .001). The values of tHcy returned to reference range in 117 subjects (51.3%) after the first cycle and in 198 (86.8%) during the follow-up. The risk of failure in tHcy level normalization was increased in patients with metabolic syndrome (hazard ratio [HR], 3.49; 95% confidence interval [CI], 1.46-8.36), higher baseline tHcy levels (HR, 1.045; 95% CI, 1.018-1.073), or methylenetetrahydrofolate reductase homozygous mutation (HR, 6.59; 95% CI, 2.64-16.4). This study clearly shows that a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 5-MTHF supplementation is able to significantly reduce tHcy levels in patients with mild/moderate HHcy.
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ambrosino
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lupoli
authors.affiliation: Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Minno
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Nardo
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Marrone
authors.affiliation: Department of Pharmacy, Federico II University, Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lupoli
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scaravilli
authors.affiliation: Department of Pharmacy, Federico II University, Naples, Italy.
authors.forename: Emma
authors.initials: E
authors.lastname: Mitidieri
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tufano
authors.affiliation: Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address: dario.diminno@hotmail.it.
authors.forename: Matteo Nicola Dario
authors.initials: MN
authors.lastname: Di Minno
mesh_terms: D000328:Adult; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood* / Q000235:genetics; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011446:Prospective Studies; D013763:Tetrahydrofolates / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D013763:Tetrahydrofolates; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate
keywords: 5-Methyl-tetra-hydro-folate; Cyclic folate supplementation; Folate; Homocysteine; Hyperhomocysteinemia; Patient