title: Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial.
abstract: BACKGROUND
  We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function.
  
  
  METHODS
  We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital. Adults (age ≥18 years) with severe sepsis or septic shock between November 2012 and January 2014 were included. Patients received 200 mg enteral ubiquinol or placebo twice a day for up to seven days. Blood draws were obtained at baseline (0 h), 12, 24, 48, and 72 h. The primary outcome of the study was change in plasma CoQ10 parameters (total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10). Secondary outcomes included assessment of: 1) vascular endothelial biomarkers, 2) inflammatory biomarkers, 3) biomarkers related to mitochondrial injury including cytochrome c levels, and 4) clinical outcomes. CoQ10 levels and biomarkers were compared between groups using repeated measures models.
  
  
  RESULTS
  We enrolled 38 patients: 19 in the CoQ10 group and 19 in the placebo group. The mean patient age was 62 ± 16 years and 47% were female. Baseline characteristics and CoQ10 levels were similar for both groups. There was a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10 in the ubiquinol group compared to the placebo group. We found no difference between the two groups in any of the secondary outcomes.
  
  
  CONCLUSIONS
  In this pilot trial we showed that plasma CoQ10 levels could be increased in patients with severe sepsis or septic shock, with the administration of oral ubiquinol. Further research is needed to address whether ubiquinol administration can result in improved clinical outcomes in this patient population.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier NCT01948063. Registered on 18 February 2013.
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, 02215, USA. mdonnino@bidmc.harvard.edu.|Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, USA. mdonnino@bidmc.harvard.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Donnino
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, 02215, USA. sharri89@hotmail.com.|Research Center for Emergency Medicine, Aarhus University Hospital, Norrebrogade 44, Aarhus, 8000, Denmark. sharri89@hotmail.com.
authors.forename: Sharri J
authors.initials: SJ
authors.lastname: Mortensen
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, 02215, USA. lwanders@bidmc.harvard.edu.|Department of Anesthesiology, Aarhus University Hospital, Norrebrogade 44, Aarhus, 8000, Denmark. lwanders@bidmc.harvard.edu.
authors.forename: Lars W
authors.initials: LW
authors.lastname: Andersen
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, 02215, USA. mchase1@bidmc.harvard.edu.
authors.forename: Maureen
authors.initials: M
authors.lastname: Chase
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, USA. kberg@bidmc.harvard.edu.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Berg
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, 02215, USA. jbalkema@bidmc.harvard.edu.
authors.forename: Julia
authors.initials: J
authors.lastname: Balkema
authors.affiliation: Resuscitation Institute at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA. jeejabai.radhakrishnan@rosalindfranklin.edu.
authors.forename: Jeejabai
authors.initials: J
authors.lastname: Radhakrishnan
authors.affiliation: Resuscitation Institute at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA. raul.gazmuri@rosalindfranklin.edu.
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Gazmuri
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, 02215, USA. xliu4@bidmc.harvard.edu.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, 02215, USA. mcocchi@bidmc.harvard.edu.|Department of Anesthesia Critical Care, Division of Critical Care, Beth Israel Deaconess Medical Center, One Deaconess Road West CC-2, Boston, MA, USA. mcocchi@bidmc.harvard.edu.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Cocchi
mesh_terms: D002784:Cholesterol / Q000097:blood; D045304:Cytochromes c / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood; D008297:Male; D018977:Micronutrients / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D007378:Interleukins; D018977:Micronutrients; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D014451:Ubiquinone; D045304:Cytochromes c; D002784:Cholesterol; C024989:coenzyme Q10; C003741:ubiquinol