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

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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.

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.

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Acknowledgements

We thank the participants who volunteered to participate in the study. Regitze Kraunsøe, Jeppe Bach, and Christina N. Hansen are thanked for expert technical assistance. Financial support from the University of Copenhagen 2016 Center of Excellence grand (The LIFESTAT study) and the Nordea Foundation is gratefully acknowledged.

Author contribution

NS, JWH, FD, and SL designed the study. MA, NS, DS, TLD, FD, and SL collected data and undertook analysis. MA, NS, DS, TLD, JWH, FD, and SL wrote and accepted the finale version of the manuscript.

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Authors and Affiliations

  1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen N, Denmark

    Magnus Asping, Nis Stride, Ditte Søgaard, Tine Lovsø Dohlmann, Jørn W. Helge, Flemming Dela & Steen Larsen

  2. Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark

    Flemming Dela

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  1. Magnus Asping
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  2. Nis Stride
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  3. Ditte Søgaard
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  4. Tine Lovsø Dohlmann
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  5. Jørn W. Helge
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  6. Flemming Dela
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  7. Steen Larsen
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Corresponding author

Correspondence to Steen Larsen.

Ethics declarations

The ethics committee of the municipality of Copenhagen and Frederiksberg in Denmark approved the study protocol (H-4-2009-095). Oral and written consent was obtained from each participant in accordance with the Helsinki Declaration.

Conflict of interest

The authors declare that they have no conflict of interest.

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Asping, M., Stride, N., Søgaard, D. et al. The effects of 2 weeks of statin treatment on mitochondrial respiratory capacity in middle-aged males: the LIFESTAT study. Eur J Clin Pharmacol 73, 679–687 (2017). https://doi.org/10.1007/s00228-017-2224-4

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  • DOI: https://doi.org/10.1007/s00228-017-2224-4

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