title: Very low oral doses of vitamin B-12 increase serum concentrations in elderly subjects with food-bound vitamin B-12 malabsorption.
abstract: The BOSSANOVA study, a randomized double-blind trial, was designed to test the ability of very low oral doses of vitamin B-12 to increase the serum vitamin B-12 concentration in elderly subjects with food-bound vitamin B-12 malabsorption, and to determine whether there was a dose response. We also aimed to quantitatively assess the most efficient dose to be added to flour in addition to folic acid (flour cofortification with vitamin B-12 and folic acid). Sixty-seven patients were randomly assigned to 1 of 6 groups receiving various daily oral doses of vitamin B-12 (i.e., 2.5, 5, 10, 20, 40, or 80 microg/d) for 30 d. The dose-response was tested for different biological variables using a mixed model, taking into account the variable's initial value (between-subject effect), a linear log-dose effect, and a linear log (dosextime) interaction, where time was d 15 or d 30. We planned to determine the amount of oral vitamin B-12 that would increase the serum vitamin B-12 concentration by 37 pmol/L (50 ng/L). Significant between-subject effects were found for serum vitamin B-12, plasma homocysteine, and methylmalonic acid concentrations, but a log-dose effect was found only for vitamin B-12 (P<0.001). The slope of the line tended to be higher (P=0.07) at d 30 than at d 15. For a mean serum vitamin B-12 increase of 37 pmol/L, a dose of 5.9 (95% CI, 0.9-12.1) microg/d was needed. We concluded that very low oral doses of vitamin B-12 increased serum vitamin B-12 concentrations in elderly subjects with subclinical vitamin B-12 deficiency, following a log-dose pattern. Our results could be beneficial in the design of a public health program for safe flour cofortification with folic acid.
authors.affiliation: INSERM U 258, Hôpital Paul Brousse, Villejuif, France. jacques.blacher@htd.aphp.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Blacher
authors.forename: Sébastien
authors.initials: S
authors.lastname: Czernichow
authors.forename: Mathilde
authors.initials: M
authors.lastname: Raphaël
authors.forename: Christophe
authors.initials: C
authors.lastname: Roussel
authors.forename: Bernadette
authors.initials: B
authors.lastname: Chadefaux-Vekemans
authors.forename: Gilles
authors.initials: G
authors.lastname: Morineau
authors.forename: Stéphane
authors.initials: S
authors.lastname: Giraudier
authors.forename: Annick
authors.initials: A
authors.lastname: Tibi
authors.forename: Olivier
authors.initials: O
authors.lastname: Henry
authors.forename: Michel
authors.initials: M
authors.lastname: Vayssière
authors.forename: Moussa
authors.initials: M
authors.lastname: Oudjhani
authors.forename: Sophie
authors.initials: S
authors.lastname: Nadaï
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vincent
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bodak
authors.forename: Claude
authors.initials: C
authors.lastname: Di Menza
authors.forename: Joël
authors.initials: J
authors.lastname: Ménard
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Zittoun
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducimetière
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008286:Malabsorption Syndromes / Q000378:metabolism*; D008297:Male; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D014806:Vitamin B 12 Deficiency / Q000178:diet therapy / Q000378:metabolism*
chemical_list: D014805:Vitamin B 12