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Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism.
J Clin Endocrinol Metab. 2018 01 01; 103(1):75-84.JC

Abstract

Context

Statin myopathy is linked to disturbances in mitochondrial function and exercise intolerance.

Objectives

To determine whether differences exist in exercise performance, muscle function, and muscle mitochondrial oxidative capacity and content between symptomatic and asymptomatic statin users, and control subjects.

Design

Cross-sectional study.

Setting

Department of Physiology, Radboud University Medical Center.

Participants

Long-term symptomatic and asymptomatic statin users, and control subjects (n = 10 per group).

Interventions

Maximal incremental cycling tests, involuntary electrically stimulated isometric quadriceps-muscle contractions, and biopsy of vastus lateralis muscle.

Main Outcomes Measured

Maximal exercise capacity, substrate use during exercise, muscle function, and mitochondrial energy metabolism.

Results

Peak oxygen uptake, maximal work load, and ventilatory efficiency were comparable between groups, but both statin groups had a depressed anaerobic threshold compared with the control group (P = 0.01). Muscle relaxation time was prolonged in both statin groups compared with the control group and rate of maximal force rise was decreased (Ptime×group < 0.001 for both measures). Mitochondrial activity of complexes II and IV was lower in symptomatic statin users than control subjects and tended to be lower for complex (C) III (CII: P = 0.03; CIII: P = 0.05; CIV: P = 0.04). Mitochondrial content tended to be lower in both statin groups than in control subjects.

Conclusion

Statin use attenuated substrate use during maximal exercise performance, induced muscle fatigue during repeated muscle contractions, and decreased muscle mitochondrial oxidative capacity. This suggests disturbances in mitochondrial oxidative capacity occur with statin use even in patients without statin-induced muscle complaints.

Authors+Show Affiliations

Department of Physiology, Radboud University Medical Center, Nijmegen, Netherlands.Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, Netherlands. Centre for Systems Biology and Bioenergetics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, Netherlands.Department of Physiology, Radboud University Medical Center, Nijmegen, Netherlands.Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, Netherlands. Centre for Systems Biology and Bioenergetics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, Netherlands.Centre for Systems Biology and Bioenergetics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, Netherlands. Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Medical Center, Nijmegen, Netherlands.Centre for Systems Biology and Bioenergetics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, Netherlands. Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Medical Center, Nijmegen, Netherlands.Division of Cardiology, Hartford Hospital, Hartford, Connecticut.Department of Physiology, Radboud University Medical Center, Nijmegen, Netherlands.Department of Physiology, Radboud University Medical Center, Nijmegen, Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29040646

Citation

Allard, Neeltje A E., et al. "Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism." The Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 1, 2018, pp. 75-84.
Allard NAE, Schirris TJJ, Verheggen RJ, et al. Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism. J Clin Endocrinol Metab. 2018;103(1):75-84.
Allard, N. A. E., Schirris, T. J. J., Verheggen, R. J., Russel, F. G. M., Rodenburg, R. J., Smeitink, J. A. M., Thompson, P. D., Hopman, M. T. E., & Timmers, S. (2018). Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism. The Journal of Clinical Endocrinology and Metabolism, 103(1), 75-84. https://doi.org/10.1210/jc.2017-01561
Allard NAE, et al. Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism. J Clin Endocrinol Metab. 2018 01 1;103(1):75-84. PubMed PMID: 29040646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism. AU - Allard,Neeltje A E, AU - Schirris,Tom J J, AU - Verheggen,Rebecca J, AU - Russel,Frans G M, AU - Rodenburg,Richard J, AU - Smeitink,Jan A M, AU - Thompson,Paul D, AU - Hopman,Maria T E, AU - Timmers,Silvie, PY - 2017/07/10/received PY - 2017/10/03/accepted PY - 2017/10/19/pubmed PY - 2018/6/27/medline PY - 2017/10/18/entrez SP - 75 EP - 84 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 103 IS - 1 N2 - Context: Statin myopathy is linked to disturbances in mitochondrial function and exercise intolerance. Objectives: To determine whether differences exist in exercise performance, muscle function, and muscle mitochondrial oxidative capacity and content between symptomatic and asymptomatic statin users, and control subjects. Design: Cross-sectional study. Setting: Department of Physiology, Radboud University Medical Center. Participants: Long-term symptomatic and asymptomatic statin users, and control subjects (n = 10 per group). Interventions: Maximal incremental cycling tests, involuntary electrically stimulated isometric quadriceps-muscle contractions, and biopsy of vastus lateralis muscle. Main Outcomes Measured: Maximal exercise capacity, substrate use during exercise, muscle function, and mitochondrial energy metabolism. Results: Peak oxygen uptake, maximal work load, and ventilatory efficiency were comparable between groups, but both statin groups had a depressed anaerobic threshold compared with the control group (P = 0.01). Muscle relaxation time was prolonged in both statin groups compared with the control group and rate of maximal force rise was decreased (Ptime×group < 0.001 for both measures). Mitochondrial activity of complexes II and IV was lower in symptomatic statin users than control subjects and tended to be lower for complex (C) III (CII: P = 0.03; CIII: P = 0.05; CIV: P = 0.04). Mitochondrial content tended to be lower in both statin groups than in control subjects. Conclusion: Statin use attenuated substrate use during maximal exercise performance, induced muscle fatigue during repeated muscle contractions, and decreased muscle mitochondrial oxidative capacity. This suggests disturbances in mitochondrial oxidative capacity occur with statin use even in patients without statin-induced muscle complaints. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/29040646/Statins_Affect_Skeletal_Muscle_Performance:_Evidence_for_Disturbances_in_Energy_Metabolism_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2017-01561 DB - PRIME DP - Unbound Medicine ER -