vitamin-b-12 and Cystic-Fibrosis

Vitamin B12 can bind two carrier proteins in the digestive tract, haptocorrin (R binder) and intrinsic factor, but only its binding to intrinsic factor allows its absorption. A malabsorption of vitamin B12 is observed in about 30% of adult patients with exocrine pancreatic insufficiency, using the Schilling test. None of the hypotheses that have tried to explain this malabsorption are entirely satisfactory. A failure to degrade haptocorrin can prevent the binding of vitamin B12 to intrinsic factor. It has also been suggested that pancreatic secretion could modify the structure of intrinsic factor, enabling the uptake of the vitamin B12-intrinsic factor complex by the ileum. Other factors can also affect the binding of vitamin B12 to intrinsic factor, such as the gastric pH and bile. The Schilling test is abnormal in nearly all cases of cystic fibrosis. One explanation could be the gastric hyperacidity observed in this disease. Despite the frequency of abnormal Schilling tests, vitamin B12 deficiency is very rare in cases of exocrine pancreatic dysfunction, in adults as well as in children with cystic fibrosis. The assimilation of this vitamin with a tracer included in food instead of the crystalline labeled cobalamin used in the Schilling test remains to be investigated.

Topics: Adult; Child; Cystic Fibrosis; Digestion; Exocrine Pancreatic Insufficiency; Humans; Malabsorption Syndromes; Schilling Test; Vitamin B 12

Topics: Abetalipoproteinemia; Acrodermatitis; Acute Disease; Age Factors; Amino Acid Metabolism, Inborn Errors; Animals; Celiac Disease; Child; Chlorides; Cystic Fibrosis; Diarrhea; Diet Therapy; Endopeptidases; Enteritis; Food Hypersensitivity; Humans; Lactose Intolerance; Malabsorption Syndromes; Metabolism, Inborn Errors; Milk; Vitamin B 12

Topics: Abetalipoproteinemia; Amino Acids; Biliary Tract Diseases; Bone Marrow Diseases; Celiac Disease; Child, Preschool; Cystic Fibrosis; Folic Acid; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Intestine, Large; Intestine, Small; Lipidoses; Magnesium; Malabsorption Syndromes; Pancreatic Diseases; Postoperative Complications; Protein-Losing Enteropathies; Sprue, Tropical; Vitamin B 12; Whipple Disease; Xanthomatosis

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Bile Acids and Salts; Cholecystokinin; Cystic Fibrosis; Enzymes; Gastric Juice; Gastrointestinal Hormones; Humans; Lipoprotein Lipase; Pancreas; Pancreatic Juice; Pancreatitis; Phospholipases; Research; Salts; Secretin; Vitamin B 12

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

Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based, and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI.. Serum B12 status was assessed in subjects (5-18 years) and categorized as elevated (serum B12 above reference range for age and sex [Hi-B12]) or within reference range (serum B12 within reference range for age and sex) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index z scores, pulmonary function, energy, and dietary and supplement-based vitamin intake were assessed.. A total of 106 subjects, mean age 10.4 ± 3.0 years, participated in the study. Median serum B12 was 1083 pg/mL, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intakes were both high representing 376% and 667% recommended dietary allowance (RDA), respectively. The Hi-B12 group had significantly greater supplement-based B12 intake than the serum B12 within reference range for age and sex group (1000% vs 583% RDA, P < 0.001). Multiple logistic regression analysis showed that high supplement-based B12 intake and age >12 years increased the risk of Hi-B12, whereas higher forced expiratory volume at 1 second (FEV1) decreased the risk (pseudo-R = 0.18, P < 0.001).. Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and forced expiratory volume at 1 second.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Cystic Fibrosis; Diet; Dietary Supplements; Exocrine Pancreatic Insufficiency; Female; Forced Expiratory Volume; Humans; Logistic Models; Male; Nutritional Status; Vitamin B 12

Information on peripheral neuropathy in children with cystic fibrosis is scanty. The etiology can be multifactorial (micronutrient deficiency, chronic hypoxia, impaired glucose tolerance, immunological, vasculopathic, critical illness).. Forty five cystic fibrosis children aged 1-18 years on vitamin E supplementation for at least 6 months underwent detailed neurological examination, serum vitamin E, vitamin B12, folate, copper levels and detailed nerve conduction studies.. The mean age of the study population was 8.35 years (±4.9 years) with 62.2% being males. Overall 22 out of 45 (48.88%,CI: 33.7-64.2) had electrophysiological evidence of peripheral neuropathy which was predominantly axonal (86.4%), sensory (50%), and polyneuropathy (95.45%). There was no significant association between status of serum micronutrients and electrophysiological evidence of peripheral neuropathy.. Patients with cystic fibrosis have electrophysiological evidence of peripheral neuropathy (predominantly axonal, sensory and polyneuropathy). There is significant association of higher chronological age with occurrence of peripheral neuropathy.

Topics: Adolescent; Child; Child, Preschool; Comorbidity; Copper; Cystic Fibrosis; Female; Folic Acid; Humans; Infant; Male; Peripheral Nervous System Diseases; Prevalence; Vitamin B 12; Vitamin E

In a recent study, the authors demonstrated the beneficial effect of proton-pump inhibitors (PPI) on fat malabsorption and bone mineral content in children with cystic fibrosis (CF). Prolonged use of PPI could result in vitamin B(12) deficiency as a consequence of impaired release of vitamin B(12) from food in a nonacid environment. The aim of this study was to evaluate the vitamin B 12 status of CF patients either treated with a PPI or not by measuring vitamin B(12) and homocysteine blood levels, the latter being a sensitive indicator of vitamin B(12) deficiency.. The study population consisted of 20 CF patients, 11 patients treated with a PPI for at least 2 years and 9 patients not treated with a PPI, and 10 healthy, age-matched control participants. Homocysteine blood levels were measured by high-performance liquid chromatography, and vitamin B(12) levels were measured by a competitive protein-binding assay.. Vitamin B(12) levels were significantly higher in both CF groups compared with the control participants (PPI+, P = 0.02; PPI-, P = 0.009). There was no significant difference in vitamin B(12) levels between both CF groups. Homocysteine levels were normal and similar in all groups.. Cystic fibrosis patients treated with a PPI for at least 2 years show no signs of vitamin B(12) deficiency.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Case-Control Studies; Child; Child, Preschool; Cystic Fibrosis; Enzyme Inhibitors; Female; Homocysteine; Humans; Lansoprazole; Male; Omeprazole; Proton Pump Inhibitors; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Absorption of crystalline labeled cobalamin is strongly decreased in cases of cystic fibrosis. In order to determine if this is due to an alteration or a lack of activation of intrinsic factor by proteases, the physicochemical properties and biological activity of intrinsic factor have been studied. Intrinsic factor was purified 800-fold from stimulated gastric juice of cystic fibrosis patients with a yield of 64.2%. Cystic fibrosis intrinsic factor had an estimated Mr of 57,000 in SDS-polyacrylamide gel electrophoresis. Its carbohydrate content resembled that of normal human intrinsic factor, except that the ratio fucose/sialic acid was higher (6.1 and 1.6, respectively) and that the content in N-acetylgalactosamine was decreased. The same alterations in carbohydrate composition were observed for Hc purified from cystic fibrosis saliva. Purified intrinsic factor from cystic fibrosis gastric juice was biologically active in vitro in the presence of ileal solubilized receptor as well as in vivo (Schilling test). The fate of iodinated cystic fibrosis intrinsic factor in guinea pig ileum studied by high-resolution radioautography was similar to that of normal intrinsic factor. In conclusion, despite modifications of the carbohydrate content of the molecule, the biological activity of intrinsic factor is not altered in cases of cystic fibrosis. The malassimilation of crystalline cobalamin observed in cystic fibrosis is due to a mechanism independent from intrinsic factor secretion.

Topics: Animals; Carbohydrates; Chromatography, Affinity; Chromatography, Ion Exchange; Cystic Fibrosis; Electrophoresis; Female; Gastric Juice; Guinea Pigs; Humans; Intrinsic Factor; Isoelectric Focusing; Pentagastrin; Transcobalamins; Vitamin B 12

The authors hypothesized the possibility of quantitative or qualitative abnormalities of amniotic fluid B12-binding proteins in cystic fibrosis. Seven cystic fibrosis and 59 normal amniotic fluids sampled between 17.5 and 18.5 gestational weeks were studied by radioimmunogel filtration, radioisotope technique, and isoelectric focusing chromatography. In normal amniotic fluid there was an increase of unsaturated B12-binding capacity from 16 to 41 weeks of gestation. There was no statistically significant difference in unsaturated B12-binding capacity, molecular weights and isoelectric points of haptocorrin, transcobalamin 2, and intrinsic factor between cystic fibrosis and normal amniotic fluid. Cobalamin-binding proteins study cannot help in the antenatal diagnosis of cystic fibrosis.

Topics: Amniotic Fluid; Chromatography, Gel; Cystic Fibrosis; Female; Humans; Isoelectric Focusing; Pregnancy; Prenatal Diagnosis; Transcobalamins; Vitamin B 12

Excretion of haptocorrin (R binder), cobalamin, and other corrinoids was studied in meconium from cystic fibrosis (n = 4), premature (n = 3), and control neonates (n = 13). Corrinoids content was 1.67 +/- 0.92 pmol/mg protein in meconium of cystic fibrosis (CF) neonates but only 0.33 +/- 0.37 and 0.48 +/- 0.47 pmol/mg protein, respectively, in that of prematures and controls. Considering its molecular mass (110,100 +/- 10,100) and its mean isoelectric point (3.67 +/- 0.20), haptocorrin remained undergraded in the meconium of CF neonates whereas it was partially degraded in the meconium of prematures and in most of the meconium from controls. Sequestration of cobalamin by undergraded haptocorrin can explain its increased excretion in CF meconium. Cobalamin-binding capacity of haptocorrin was 22.13 +/- 15.50 pmol/mg protein in CF meconium and about 400-fold lower in meconium of prematures and controls. This may correspond to a fetal intestinal hypersecretion in cases of CF.

Topics: Cystic Fibrosis; Glucosidases; Humans; Infant, Newborn; Infant, Premature; Meconium; Transcobalamins; Vitamin B 12

Topics: Absorption; Cystic Fibrosis; Humans; Vitamin B 12

Vitamin B12 absorption was measured in 30 patients with cystic fibrosis by means of the urinary excretion method and found to be impaired, i.e. less than 10%, in 25. The mean urinary excretion amounted to 4.7 +/- 0.8%. In all patients vitamin B12 absorption improved by the addition of trypsin (18.9 +/- 2.1%). Addition of the vitamin B12 analogue cobinamide, which prevents vitamin B12-binding by R-binders, raised the vitamin B12 absorption to 15.0 +/- 2.2%. A further improvement was obtained by the simultaneous addition of cobinamide and trypsin, 18.2 +/- 2.6%, the same value as with trypsin alone. Assuming that cobinamide addition was effective in suppressing all R-binder activity, the additional effect of trypsin suggests a second, stimulatory function of trypsin on vitamin B12 absorption, separate from R-binder-inactivation. In 5 patients only marginal improvement of vitamin B12 absorption was gained by the addition of either trypsin or cobinamide. The deficient serum vitamin B12 (110 pmol/l) in one of them indicates that the normal pancreas-substitution therapy not always implies sufficient restoration of vitamin B12 absorption.

Topics: Adolescent; Child; Child, Preschool; Cobamides; Cystic Fibrosis; Drug Therapy, Combination; Exocrine Pancreatic Insufficiency; Humans; Trypsin; Vitamin B 12

In 62 patients with cystic fibrosis the serum vitamin B12 concentration ranged from 160-2600 pmol/l with a mean of 1 105 pmol/l. Both vitamin B12-binding proteins in the serum, transcobalamin II and R-binders, carried increased amounts of vitamin B12, but showed relatively normal levels of unsaturated vitamin B12-binding capacity. This combination is rather typical for hepatic dysfunction, although the recurrent pulmonary infections might exert an upward effect on plasma R-binder concentration through increased turnover of myeloid cells. A significant positive correlation between transcobalamin II-vitamin B12 and serum alkaline phosphatase suggests that transcobalamin II-bound vitamin B12 might be an early indicator of focal biliary cirrhosis, which is known to occur in these patients.

Topics: Adolescent; Alkaline Phosphatase; Aspartate Aminotransferases; Child; Child, Preschool; Cystic Fibrosis; Humans; Transcobalamins; Vitamin B 12

A malabsorption of crystalline labelled cobalamin is observed in 100% of cystic fibrosis patients. Using radioisotope dilution assays and molecular sieve gel chromatography, we determined the serum concentration and the faecal excretion of cobalamin and cobalamin analogues in nine cystic fibrosis children before and after 4 days' interruption of pancreatic extract treatment. On chromatography, the unsaturated cobalamin binders of the faecal extracts eluted in two positions with molecular masses of 44 300 and 20 300, corresponding mostly to partially degraded R binders. The amounts of the less degraded form of R binder (molecular mass 44 300) increased significantly after interruption of the treatment. The cobalamin concentration in the serum remained normal after interruption of the treatment but the analogue concentrations in the serum decreased and faecal excretion of cobalamin and analogues increased significantly. These results allowed us to suggest that (1) pancreatic insufficiency in cystic fibrosis is responsible for a decrease in the absorption of digestive analogues induced by a defective degradation of R binders, and (2) cobalamin analogues have a short half-life in blood.

Topics: Adolescent; Carrier Proteins; Child; Child, Preschool; Chromatography, Gel; Cystic Fibrosis; Feces; Half-Life; Humans; Intestinal Absorption; Intrinsic Factor; Pancreatic Extracts; Vitamin B 12

The absorption of vitamin B12, labelled with radioactive 58Co, was measured in 19 patients with cystic fibrosis and one child with the Shwachman-Diamond syndrome using the whole body counting technique. We found vitamin B12 absorption reduced to 7.97 on average, compared to 59.2% for the control group. The low vitamin B12 absorption correlated well with the reduced fat retention coefficients. After adding 0.212 pancreatin to the radioactive vitamin B12 test dose, the absorption quotas improved in all cases, the average being 61%. A meal poor in vitamin B12 tended to increase the absorption of the radioactive test dose to 23% on average. As yet there is no satisfactory explanation for the effect of the diet on the absorption of vitamin B12 in exocrine pancreatic insufficiency. This could be the reason why the malabsorption of vitamin B12 in patients with EPI can go unnoticed for many years and could possibly explain why vitamin B12 malabsorption in exocrine pancreatic insufficiency does not cause symptoms and signs of vitamin B12 deficiency for many years.

Topics: Adolescent; Child; Child, Preschool; Cobalt Radioisotopes; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Humans; Infant; Intestinal Absorption; Male; Vitamin B 12

Topics: Biological Availability; Child; Child, Preschool; Cobalt Radioisotopes; Cystic Fibrosis; Dietary Proteins; Food; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Iron Radioisotopes; Liver; Meat; Pancreatin; Protein Binding; Radioisotopes; Selenium; Selenomethionine; Vitamin B 12; Vitamin B 12 Deficiency; Whole-Body Counting

Fifty cystic fibrosis (CF) patients, of whom 9 had multilobular cirrhosis, were observed regularly for a period of 3 years and various liver function tests, indicating cytolysis, cholestasis and cellular insufficiency were performed. Immunoglobulin and prothrombin were assayed. In 9 patients with cirrhosis, the tests were generally abnormal. Two distinct biochemical patterns of cirrhosis were distinguished, one clearly cholestatic and the other of a more cellular type. The distinction was made on the basis of the IgA : Transferrin ratio and of gamma-glutamyl-transpeptidase levels. In the non-cirrhotic patients, a temporary increase of cytolysis and cholestasis was observed in 50% of the cases.

Topics: Adolescent; Adult; Alanine Transaminase; Alkaline Phosphatase; Child; Child, Preschool; Cholinesterases; Cystic Fibrosis; Female; gamma-Glutamyltransferase; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Infant; Leucyl Aminopeptidase; Liver; Liver Cirrhosis; Liver Function Tests; Male; Ornithine Carbamoyltransferase; Prothrombin; Serum Albumin; Transferrin; Vitamin B 12

Topics: Abetalipoproteinemia; Acrodermatitis; Amino Acid Metabolism, Inborn Errors; Amino Acids; Amylases; Amyloidosis; Carbohydrate Metabolism, Inborn Errors; Copper; Cystic Fibrosis; Cystinuria; Diarrhea; Fanconi Syndrome; Fats; Folic Acid; Fructose Intolerance; Glucosidases; Hartnup Disease; Humans; Intestinal Absorption; Lactose Intolerance; Magnesium; Malabsorption Syndromes; Monosaccharides; Pancreatitis; Phenylketonurias; Rickets; Vitamin B 12

Topics: Adolescent; Adult; Bicarbonates; Child; Cobalt Isotopes; Crystallization; Cystic Fibrosis; Fats; Feces; Humans; Intestinal Absorption; Isotope Labeling; Pancreas; Pancreatic Extracts; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Child; Cystic Fibrosis; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Cystic Fibrosis; Female; Humans; Intestinal Absorption; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Child; Chloramphenicol; Cystic Fibrosis; Female; Humans; Optic Neuritis; Pyridoxine; Vitamin B 12