title: Absorption and retention of free and milk protein-bound cyano- and hydroxocobalamins. An experimental study in rats.
abstract: BACKGROUND
  Cobalamin/Vitamin B12 (Cbl) is an essential vitamin, supplied mainly as hydroxocobalamin (OHCbl) by animal products, including cows' milk. Cyanocobalamin (CNCbl) is the usual form in vitamin pills. The aim was to explore absorption and tissue accumulation of two Cbl forms, administered alone or bound to milk protein.
  
  
  METHODS
  We synthesized labeled OH[(57)Co]Cbl from commercially available CN[(57)Co]Cbl. Recombinant bovine transcobalamin (rbTC) was produced in yeast and skimmed milk obtained off the shelf. Male Wistar rats (250-300 g) received labeled Cbl by gastric gavage. First, we administered CN[(57)Co]Cbl, free or rbTC-bound (n = 15 in each group). Rats were sacrificed after two, 24, and 48 h. In the following studies, rats were sacrificed after 24 h. We compared absorption of free or rbTC-bound CN[(57)Co]Cbl added to cows' milk and analogous absorption of OH[(57)Co]Cbl, free or rbTC-bound, to absorption of free CN[(57)Co]Cbl, (n = 10 in each group). Blood, tissues, 24-h urine and feces were collected. Labeled Cbl was measured using a gamma counter. Results are expressed as percentage of administered dose.
  
  
  RESULTS
  Absorptions of CNCbl and OHCbl were neither influenced by rbTC-binding nor administration in milk. Absorption increased in the first 24 h with no further tissue accumulation during the subsequent 24 h. Accumulation of free CNCbl and (OHCbl) was 1.4, (4.1) (liver); 20.2, (16.4) (kidney); and 0.05, (0.02) (plasma)% 24 h after administration. Total organ accumulations were 21.6, (20.5)%. While total accumulations of CNCbl and OHCbl were equal, distributions between liver, kidney, and plasma showed significant differences (p < 0.0001; p = 0.01; p < 0.0001).
  
  
  CONCLUSIONS
  Cbl added to milk (spiked with rbTC) has high bioavailability matching that of free Cbl. OHCbl and CNCbl are absorbed equally well, but much more OHCbl accumulated in the liver. Benefits of oral supplementation with OHCbl compared to CNCbl should be investigated.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. Electronic address: lindajen@rm.dk.
authors.forename: L S
authors.initials: LS
authors.lastname: Kornerup
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: C B
authors.initials: CB
authors.lastname: Juul
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: S N
authors.initials: SN
authors.lastname: Fedosov
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: C W
authors.initials: CW
authors.lastname: Heegaard
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Greibe
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Nexo
mesh_terms: D000327:Adsorption; D000818:Animals; D002417:Cattle; D008297:Male; D008894:Milk Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014155:Transcobalamins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014805:Vitamin B 12 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D008894:Milk Proteins; D011994:Recombinant Proteins; D014155:Transcobalamins; D014805:Vitamin B 12
keywords: Cobalamin; Cyanocobalamin; Hydroxocobalamin; Intestinal absorption; Rat; Transcobalamin; Vitamin B12