Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Abstract

BackgroundCystic 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.Methodology and Principal FindingsA 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.Conclusion and Significance5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.Trial RegistrationClinicalTrials.gov NCT00730509

A Novel Lipidomic Strategy Reveals Plasma Phospholipid Signatures Associated with Respiratory Disease Severity in Cystic Fibrosis Patients

“…Reduced ratios of S-adenosylmethionine to S-adenosylhomocysteine and of PC to phosphatidylethanolamine in plasma, and phospholipid malabsorption have also been reported in CF children [36]. These altered values are reversed by PC treatment [36] and also by administration of 5-methyltetrahydrofolate [37]. Another enzyme involved in PC synthesis is CTP∶phosphocholine cytidylyltransferase.…”

Vitamin B12 Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

“…It is unclear whether there are clinical benefits of B 12 intake beyond that to sustain a normal B 12 status. Scambi et al (33) reported improvements in phospholipid docosahexaenoic acid (DHA) status in young children with CF with daily 5‐methyltetrahydrofolate (7.5 mg) and B 12 (0.5 mg) supplementation in a 24‐week intervention. The phospholipid DHA improvement was thought to be a result of the interaction of folate, B 12 , phospholipid DHA, and 1‐methyl metabolic pathway (33).…”

Functional cobalamin (vitamin B12) deficiency: role of advanced age and disorders associated with increased oxidative stress

“…14 It is noteworthy then that Cbl is an active superoxide scavenger; 15,16 reduced forms of Cbl are required for its coenzyme activity; 2 cellular uptake of Cbl may be impaired by oxidative byproducts; 17 and functional Cbl deficiency occurs after exercise and in many other pro-oxidant disorders. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Significantly, diabetes and folate excess, both of which are associated with increased oxidative stress, have been linked to functional Cbl deficiency in the elderly but not in younger individuals. 10,18,21 These observations suggest that functional Cbl deficiency may be associated with oxidative stress and that this relationship may be particularly prevalent in the elderly.…”