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Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression: Statin myalgia, muscle

Selby, Anna; Murton, Andrew; Mallinson, Joanne E.; Marimuthu, Kanagaraj; Murton, Andrew J.; Selby, Anna L.; Smith, Kenneth; Constantin-Teodosiu, Dumitru; Rennie, Michael J.; Greenhaff, Paul L.

Authors

Anna Selby

Andrew Murton

Joanne E. Mallinson

Kanagaraj Marimuthu

Andrew J. Murton

Anna L. Selby

KENNETH SMITH KEN.SMITH@NOTTINGHAM.AC.UK
Professor of Metabolic Mass Spectrometry

Dumitru Constantin-Teodosiu

Michael J. Rennie



Abstract

Statins are associated with muscle myalgia and myopathy, which probably reduce habitual physical activity. This is particularly relevant to older people who are less active, sarcopaenic and at increased risk of statin myalgia. We hypothesised that statin myalgia would be allied to impaired strength and work capacity in older people, and determined whether differences aligned with divergences in lean mass, protein turnover, insulin sensitivity and the molecular regulation of these processes. Knee extensor strength and work output during 30 maximal isokinetic contractions were assessed in healthy male volunteers, nine with no statin use (control 70.4 ± 0.7 years) and nine with statin myalgia (71.5 ± 0.9 years). Whole body and leg glucose disposal, muscle myofibrillar protein synthesis (MPS) and leg protein breakdown (LPB) were measured during fasting (≈5 mU l(-1) insulin) and fed (≈40 mU l(-1) insulin + hyperaminoacidaemia) euglyceamic clamps. Muscle biopsies were taken before and after each clamp. Lean mass, MPS, LPB and strength were not different but work output during the initial three isokinetic contractions was 19% lower (P < 0.05) in statin myalgic subjects due to a delay in time to reach peak power output. Statin myalgic subjects had reduced whole body (P = 0.05) and leg (P < 0.01) glucose disposal, greater abdominal adiposity (P < 0.05) and differential expression of 33 muscle mRNAs (5% false discovery rate (FDR)), six of which, linked to mitochondrial dysfunction and apoptosis, increased at 1% FDR. Statin myalgia was associated with impaired muscle function, increased abdominal adiposity, whole body and leg insulin resistance, and evidence of mitochondrial dysfunction and apoptosis.

Citation

Selby, A., Murton, A., Mallinson, J. E., Marimuthu, K., Murton, A. J., Selby, A. L., …Greenhaff, P. L. (2015). Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression: Statin myalgia, muscle function and metabolism. Journal of Physiology, 593(5), 1239-1257. https://doi.org/10.1113/jphysiol.2014.285577

Journal Article Type Article
Acceptance Date Dec 19, 2014
Online Publication Date Jan 26, 2015
Publication Date Mar 1, 2015
Deposit Date Jul 19, 2016
Publicly Available Date Dec 3, 2018
Journal The Journal of Physiology
Print ISSN 0022-3751
Electronic ISSN 1469-7793
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 593
Issue 5
Pages 1239-1257
DOI https://doi.org/10.1113/jphysiol.2014.285577
Public URL http://eprints.nottingham.ac.uk/id/eprint/35100
Publisher URL http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.285577/abstract
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0