title: The effects of 2 weeks of statin treatment on mitochondrial respiratory capacity in middle-aged males: the LIFESTAT study.
abstract: BACKGROUND
  Statins are used to lower cholesterol in plasma and are one of the most used drugs in the world. Many statin users experience muscle pain, but the mechanisms are unknown at the moment. Many studies have hypothesized that mitochondrial function could be involved in these side effects.
  
  
  OBJECTIVE
  The aim of the study was to investigate mitochondrial function after 2 weeks of treatment with simvastatin (S; n = 10) or pravastatin (P; n = 10) in healthy middle-aged participants.
  
  
  METHODS
  Mitochondrial respiratory capacity and substrate sensitivity were measured in permeabilized muscle fibers by high-resolution respirometry. Mitochondrial content (citrate synthase (CS) activity), antioxidant content, as well as coenzyme Q10concentration (Q10) were determined. Fasting plasma glucose and insulin concentrations were measured, and whole body maximal oxygen uptake (VO2max) was determined.
  
  
  RESULTS
  No differences were seen in mitochondrial respiratory capacity although a tendency was observed for a reduction when complex IV respiration was analyzed in both S (229 (169; 289 (95% confidence interval)) vs. 179 (146; 211) pmol/s/mg, respectively; P = 0.062) and P (214 (143; 285) vs. 162 (104; 220) pmol/s/mg, respectively; P = 0.053) after treatment. A tendency (1.64 (1.28; 2.00) vs. 1.28 (0.99; 1.58) mM, respectively; P = 0.092) for an increased mitochondrial substrate sensitivity (complex I-linked substrate; glutamate) was seen only in S after treatment. No differences were seen in Q10, CS activity, or antioxidant content after treatment. Fasting glucose and insulin as well as VO2maxwere not changed after treatment.
  
  
  CONCLUSIONS
  Two weeks of statin (S or P) treatment have no major effect on mitochondrial function. The tendency for an increased mitochondrial substrate sensitivity after simvastatin treatment could be an early indication of the negative effects linked to statin treatment.
authors.affiliation: Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark.
authors.forename: Magnus
authors.initials: M
authors.lastname: Asping
authors.affiliation: Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark.
authors.forename: Nis
authors.initials: N
authors.lastname: Stride
authors.affiliation: Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Søgaard
authors.affiliation: Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark.
authors.forename: Tine Lovsø
authors.initials: TL
authors.lastname: Dohlmann
authors.affiliation: Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark.
authors.forename: Jørn W
authors.initials: JW
authors.lastname: Helge
authors.affiliation: Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark.|Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
authors.affiliation: Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark. stelar@sund.ku.dk.
authors.forename: Steen
authors.identifier: http://orcid.org/0000-0002-5170-4337
authors.initials: S
authors.lastname: Larsen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D017035:Pravastatin / Q000008:administration & dosage / Q000009:adverse effects*; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D014451:Ubiquinone; D019821:Simvastatin; C024989:coenzyme Q10; D017035:Pravastatin
keywords: Human; Mitochondrial function; Side effects; Skeletal muscle; Statins