title: Human pharmacokinetics of high dose oral curcumin and its effect on heme oxygenase-1 expression in healthy male subjects.
abstract: OBJECTIVE
  Heme oxygenase-1 (HO-1) has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism.
  
  
  METHODS
  In an open label uncontrolled phase-1 pilot study, ten male subjects received 12 g of oral curcumin. To investigate the effects of the GT length polymorphism on the inducibility of HO-1, five subjects with homozygous short and five with homozygous long GT genotypes were studied. Plasma concentrations of curcumin, bilirubin, HO-1 mRNA, and protein expression in peripheral blood mononuclear cells (PBMCs) were analyzed over 48 hours.
  
  
  RESULTS
  At a detection limit of 1 µg/mL curcumin could not be detected in plasma of any subject. Compared to baseline, HO-1 mRNA and protein levels were not induced in PBMCs at any time point up to 48 hours. There was no correlation between any of the parameters and GT length polymorphism.
  
  
  CONCLUSIONS
  Oral curcumin administration has low bioavailability and does not induce HO-1 on mRNA or protein level in PBMCs.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Uros
authors.initials: U
authors.lastname: Klickovic
authors.affiliation: Department of Pulmonary Medicine, Wilhelminenspital Vienna, 1160 Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Doberer
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Gouya
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Aschauer
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weisshaar
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Angela
authors.identifier: 0000-0003-1341-2277
authors.initials: A
authors.lastname: Storka
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001663:Bilirubin / Q000097:blood; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006262:Health; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D051547:Heme Oxygenase-1; D003474:Curcumin; D001663:Bilirubin