Preliminary evidence for cell membrane amelioration in children with cystic fibrosis by 5-MTHF and vitamin B12 supplementation: a single arm trial.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.


BACKGROUND
ClinicalTrials.gov NCT00730509.
Scambi
Cinzia
C
Department of Clinical and Experimental Medicine, Section of Rheumatology & Internal Medicine, University of Verona, Verona, Italy. cinzia.scambi@medicina.univr.it
De Franceschi
Lucia
L
Guarini
Patrizia
P
Poli
Fabio
F
Siciliano
Angela
A
Pattini
Patrizia
P
Biondani
Andrea
A
La Verde
Valentina
V
Bortolami
Oscar
O
Turrini
Francesco
F
Carta
Franco
F
D'Orazio
Ciro
C
Assael
Baroukh M
BM
Faccini
Giovanni
G
Bambara
Lisa M
LM
D017920:Antiporters / Q000097:blood; D002412:Cations / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D019587:Dietary Supplements; D004910:Erythrocyte Membrane / Q000187:drug effects*; D004912:Erythrocytes / Q000737:chemistry / Q000648:ultrastructure; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000032:analysis; D018384:Oxidative Stress; D010743:Phospholipids / Q000097:blood; D013763:Tetrahydrofolates / Q000097:blood / Q000627:therapeutic use*; D014805:Vitamin B 12 / Q000627:therapeutic use*
D017920:Antiporters; D002412:Cations; D018840:HSP70 Heat-Shock Proteins; D008563:Membrane Lipids; D010743:Phospholipids; D013763:Tetrahydrofolates; D006710:Homocysteine; D008315:Malondialdehyde; D014805:Vitamin B 12; C005984:5-methyltetrahydrofolate