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The effects of 2 weeks of statin treatment on mitochondrial respiratory capacity in middle-aged males: the LIFESTAT study

Content Provider	Springer Nature Link
Author	Asping, Magnus Stride, Nis Søgaard, Ditte Dohlmann, Tine Lovsø Helge, Jørn W. Dela, Flemming Larsen, Steen
Copyright Year	2017
Abstract	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.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.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 Q10 concentration (Q10) were determined. Fasting plasma glucose and insulin concentrations were measured, and whole body maximal oxygen uptake (VO2max) was determined.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 VO2max were not changed after treatment.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.
Starting Page	679
Ending Page	687
Page Count	9
File Format	PDF
ISSN	00316970
Journal	European Journal of Clinical Pharmacology
Volume Number	73
Issue Number	6
e-ISSN	14321041
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-02-28
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Mitochondrial function Side effects Skeletal muscle Statins Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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