title: Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12deficiency with neurological symptoms.
abstract: The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB12) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B12-deficient patients (vit B12< 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B12level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose-dependent manner with HB12. The apparent permeability of Hdrx was Papp= 34.9 ± 4.6 × 10-6cm/s in the presence of 3 mg/mL (HB12B) compared to the control Papp= 6.2 ± 0.7 × 10-6cm/s. (ii) Total transepithelial electrical conductance (Gt) increased in dose-dependent manner with HB12, Gt= 161.5 ± 10.8 mS/cm² with HB12B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, Gt= 28.7 ± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS.
authors.affiliation: Neurology Department, Hassan II University Hospital, Route de Sidi Harem, 30000 Fez, Morocco.|Laboratory of Clinical Neuroscience, Faculty of Medicine and Pharmacy of Fez, Sidi Mohamed Ben Abdellah University, Route de Sidi Harem, 30000 Fez, Morocco.
authors.forename: Zouhayr
authors.initials: Z
authors.lastname: Souirti
authors.affiliation: Neurology Department, Hassan II University Hospital, Route de Sidi Harem, 30000 Fez, Morocco.
authors.forename: Mouna
authors.initials: M
authors.lastname: Loukili
authors.affiliation: TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris 7, 75890 Paris Cedex 18, France.|Biotechnopôle IRED, Ndjaména and Institut Universitaire des Sciences et Techniques d'Abéché, B.P. 433 N'Djaména, Tchad.
authors.forename: Imar D
authors.initials: ID
authors.lastname: Soudy
authors.affiliation: TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris 7, 75890 Paris Cedex 18, France.|Physiology and Nutrition Laboratory, Faculté des Sciences de Tunis, Tunis 2092, Tunisia.
authors.forename: Kaies
authors.initials: K
authors.lastname: Rtibi
authors.affiliation: TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris 7, 75890 Paris Cedex 18, France.
authors.forename: Aslihan
authors.initials: A
authors.lastname: Özel
authors.affiliation: TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris 7, 75890 Paris Cedex 18, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Limas-Nzouzi
authors.affiliation: Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, Faculty of Sciences Dhar El Mehraz, B.P. 1796, Fès - Atlas - Morocco.
authors.forename: Seloua
authors.initials: S
authors.lastname: El Ouezzani
authors.affiliation: TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris 7, 75890 Paris Cedex 18, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Eto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D041743:Herb-Drug Interactions; D031584:Hibiscus / Q000737:chemistry*; D006801:Humans; D006879:Hydroxocobalamin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009422:Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism; D000069459:Teas, Herbal; D014806:Vitamin B 12 Deficiency / Q000188:drug therapy* / Q000378:metabolism; D014803:Vitamin B Complex / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D000069459:Teas, Herbal; D014803:Vitamin B Complex; D006879:Hydroxocobalamin
keywords: 
  Hibiscus sabdariffa
  ; cobalamin; hydroxocobalamin; intestinal bioavailability; ionic conductance; mice; neurological deficit; pernicious anaemia; pharmacological enhancer; vitamin B12