title: Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress.
abstract: BACKGROUND
  Coenzyme Q10 (CoQ10) supplementation improves mitochondrial coupling of respiration to oxidative phosphorylation, decreases superoxide production in endothelial cells, and may improve functional cardiac capacity in patients with congestive heart failure. There are no studies evaluating the safety, tolerability and efficacy of varying doses of CoQ10 in chronic hemodialysis patients, a population subject to increased oxidative stress.
  
  
  METHODS
  We performed a dose escalation study to test the hypothesis that CoQ10 therapy is safe, well-tolerated, and improves biomarkers of oxidative stress in patients receiving hemodialysis therapy. Plasma concentrations of F2-isoprostanes and isofurans were measured to assess systemic oxidative stress and plasma CoQ10 concentrations were measured to determine dose, concentration and response relationships.
  
  
  RESULTS
  Fifteen of the 20 subjects completed the entire dose escalation sequence. Mean CoQ10 levels increased in a linear fashion from 704 ± 286 ng/mL at baseline to 4033 ± 1637 ng/mL, and plasma isofuran concentrations decreased from 141 ± 67.5 pg/mL at baseline to 72.2 ± 37.5 pg/mL at the completion of the study (P = 0.003 vs. baseline and P < 0.001 for the effect of dose escalation on isofurans). Plasma F2-isoprostane concentrations did not change during the study.
  
  
  CONCLUSIONS
  CoQ10 supplementation at doses as high as 1800 mg per day was safe in all subjects and well-tolerated in most. Short-term daily CoQ10 supplementation decreased plasma isofuran concentrations in a dose dependent manner. CoQ10 supplementation may improve mitochondrial function and decrease oxidative stress in patients receiving hemodialysis.
  
  
  BACKGROUND
  This clinical trial was registered on clinicaltrials.gov [NCT00908297] on May 21, 2009.
authors.affiliation: Department of Pharmacy, University of Washington School of Pharmacy, Box 357630, Seattle, WA, 98195, USA. cathyy@uw.edu.|Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. cathyy@uw.edu.
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Yeung
authors.affiliation: Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Avenue South, 526 Medical Arts Building, Nashville, TN, 37205, USA. frederic.t.billings@vanderbilt.edu.
authors.forename: Frederic T
authors.initials: FT
authors.lastname: Billings
authors.affiliation: Department of Pharmacy, University of Washington School of Pharmacy, Box 357630, Seattle, WA, 98195, USA. adam.claessens@tu.edu.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Claessens
authors.affiliation: Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. broshanr@uw.edu.
authors.forename: Baback
authors.initials: B
authors.lastname: Roshanravan
authors.affiliation: Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. loril@nwkidney.org.
authors.forename: Lori
authors.initials: L
authors.lastname: Linke
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, S-3223 Medical Center North, Nashville, TN, 37232, USA. mary.b.sundell@vanderbilt.edu.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Sundell
authors.affiliation: Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. sahmad@uw.edu.
authors.forename: Suhail
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Box 358055, Seattle, WA, USA. bhshao@u.washington.edu.
authors.forename: Baohai
authors.initials: B
authors.lastname: Shao
authors.affiliation: Department of Pharmacy, University of Washington School of Pharmacy, Box 357630, Seattle, WA, 98195, USA. ds@uw.edu.
authors.forename: Danny D
authors.initials: DD
authors.lastname: Shen
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, S-3223 Medical Center North, Nashville, TN, 37232, USA. alp.ikizler@vanderbilt.edu.
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.affiliation: Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. himmej@u.washington.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008452:Maximum Allowable Concentration; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D006435:Renal Dialysis / Q000379:methods*; D014451:Ubiquinone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014481:United States; D055815:Young Adult
chemical_list: D014451:Ubiquinone; C024989:coenzyme Q10