title: A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement.
abstract: BACKGROUND
  Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial.
  
  
  METHODS
  The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function.
  
  
  RESULTS
  A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression.
  
  
  CONCLUSIONS
  This study suggests that Ambrotose AO(R) capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT).
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trials Register: ACTRN12605000258651.
authors.affiliation: Australian Centre for Complementary Medicine Education and Research, A Joint Venture of the University of Queensland and Southern Cross University, Lismore, Australia. smyers@scu.edu.au
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Myers
authors.forename: Lesley
authors.initials: L
authors.lastname: Stevenson
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Cheras
authors.forename: Joan
authors.initials: J
authors.lastname: O'Connor
authors.forename: Lyndon
authors.initials: L
authors.lastname: Brooks
authors.forename: Margaret
authors.initials: M
authors.lastname: Rolfe
authors.forename: Paul
authors.initials: P
authors.lastname: Conellan
authors.forename: Carol
authors.initials: C
authors.lastname: Morris
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D028241:Camellia sinensis; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*; D027843:Vitis; D055815:Young Adult
chemical_list: D000975:Antioxidants; D007155:Immunologic Factors; D010936:Plant Extracts; D014815:Vitamins; D014810:Vitamin E; D011794:Quercetin; D051546:Cyclooxygenase 2; D010100:Oxygen