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

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Magnus Asping, Nis Stride, Ditte Sogaard, Tine Lovso Dohlmann, Jorn W. Helge, Flemming Dela, Steen Larsen

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.

Aim
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 Q10 concentration (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 VO2max were not changed after treatment.

Conclusion
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.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Clinical Pharmacology
Vol/bind73
Udgave nummer6
Sider (fra-til)679-687
ISSN0031-6970
DOI
StatusUdgivet - jun. 2017

ID: 183825271