5-methyltetrahydrofolate and Cystic-Fibrosis

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.. A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.. 5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.. ClinicalTrials.gov NCT00730509.

Topics: Antiporters; Cations; Child; Child, Preschool; Cystic Fibrosis; Dietary Supplements; Erythrocyte Membrane; Erythrocytes; Female; Homocysteine; HSP70 Heat-Shock Proteins; Humans; Ion Transport; Male; Malondialdehyde; Membrane Fluidity; Membrane Lipids; Oxidative Stress; Phospholipids; Tetrahydrofolates; Vitamin B 12

Recent studies have reported an imbalance between n6 and n3 fatty acids (AA and DHA) in subjects with CF. Alterations in fatty acid amounts are present in CFTR-expressing tissues, plasma and in circulating blood cells. It has been reported that the correction of polyunsaturated fatty acid deficiency reversed the organ pathologies observed in CF knockout mice. We describe a CF child with an unusual clinical course presenting high molar percentage of DHA in plasma and red cells membrane during supplementation with 5-methyltetrahydrofolate and vitamin B12.

Topics: Adult; Chymotrypsin; Cystic Fibrosis; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-6; Female; Folic Acid; Humans; Infant, Newborn; Methylation; Milk, Human; Tetrahydrofolates