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

Key points: Statins cause muscle-specific side effects, most commonly muscle aches/weakness (myalgia), particularly in older people. Furthermore, evidence has linked statin use to increased risk of type 2 diabetes. However, the mechanisms involved are unknown. This is the first study to measure muscle protein turnover rates and insulin sensitivity in statin myalgic volunteers and age-matched, non-statin users under controlled fasting and fed conditions using gold standard methods. We demonstrate in older people that chronic statin myalgia is not associated with deficits in muscle strength and lean mass or the dysregulation of muscle protein turnover compared to non-statin users. Furthermore, there were no between-group differences in blood or muscle inflammatory markers. Statin users did, however, show blunting of muscle power output at the onset of dynamic exercise, increased abdominal adiposity, whole body and leg insulin resistance, and clear differential expression of muscle genes linked to mitochondrial dysfunction and apoptosis, which warrant further investigation. 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.