Chart 1.
Description of the studies investigating the effect of statins and physical exercise on skeletal muscle
| Reference | Sample | Drug therapy | Physical exercise protocol | Results |
|---|---|---|---|---|
| Use of statins in athletes | ||||
| Parker et al.37 | n = 80 individuals (59♂ and 21♀) | Different statin types and doses (n = 37) | Running a marathon | Increase in CK after 24 horas in the statin group |
| Statins and acute physical exercises | ||||
| Thompson et al.38 | n = 59 men (18-65 years) Double-blind randomized trial | Lovastatin (40 mg/day; n = 22) or placebo (n = 27) for 5 weeks | Treadmill (45'; 15% incline; 65% HRmax) | Increase in CK 24 and 48 hours after the walk in the lovastatin group |
| Elbow flexion (4x10 repetitions; 50% MF) | ||||
| Reust et al.39 | n = 10 men (27-28 years) Double-blind crossover randomized trial | Lovastatin (40 mg/day; n = 5) or placebo (n = 5) for 30 days | Treadmill (60'; 14% incline; 3 km/h) | Maintenance of CK after lovastatin compared with placebo |
| Kearns et al.40 | n = 79 men Randomized trial | Atorvastatin (10 mg/day, n = 42; or 80 mg/day, n = 37) for 5 weeks | Treadmill (3x15'; 15% incline; 65% HRmax) | ↑ total CK, CK-MB and muscular pain after exercise |
| Panayiotou et al.41 | n = 28 sedentary men (> 65 years) | Atorvastatin (10-80 mg/day; n = 14) for ≥ 1 year | Knee extension (5x8 maximum EC; 2 sessions) | Similar muscular function between groups |
| Urso et al.42 | n = 8 sedentary men (18-30 years) Randomized double-blind trial | Atorvastatin (80 mg/day; n = 4) or placebo (n = 4) for 4 weeks | Knee extension (300 EC) before and after treatment | Different expression of genes from the PSU pathway of catabolism and of apoptosis |
| Statins and chronic physical exercises | ||||
| Accioly et al.43 | n = 80 male rats (hyperlipidic diet, n = 60; standard diet, n = 20) in 8 groups | Simvastatin (20 mg, n = 20), Fluvastatin (10 mg, n = 20) or placebo (n = 20) | Treadmill (60'; 9.75 m/min) 5x/week for 8 weeks | Higher frequency of morphological alterations after statin, with or without exercise |
| Seachrist et al.44 | n = 48 female rats divided into 8 groups | Cerivastatin (0.1; 0.5; 1.0 mg/kg/day) or placebo for 14 days | Treadmill (25'; 20 m/minute; 15° of incline angle) 5x/week for 2 weeks | Exacerbation of muscular degeneration; mitochondrial involvement |
| Meex et al.45 | n = 38 sedentary elderly men | Different types and doses of statins (n = 14) | Cycloergometer (30'; 55% ML) 2x/week and 8 resistance exercises (3x8 repetitions; 55 and 75%) 1x/week, 12 weeks | Increase in ML, muscular strength, muscular density and mitochondrial function in both groups |
| Mikus et al.46 | n = 37 sedentary individuals with risk factor for MS (13♂ and 24♀: 25-59 years) | Simvastatin (40 mg/day) (n = 19) | Treadmill (45'; 60-75% rHR) 5x/ week for 12 weeks | Increase in LM and decrease in muscular citrate synthase activity |
| Coen et al.47 | n = 31 sedentary individuals (15♂ and 16♀; 40-65 years) Randomized trial | Rosuvastatin (10 mg/day) for 20 weeks | Treadmill (20'; 60-70% rHR) and 8 resistance exercises (70-80% 1MR), 3x/weeks for 10 weeks | Increase in CK 48 hours after the 1st session; absence of reports of pain/fatigue |
| Mechanisms of muscular responses to statins and to physical exercises | ||||
| Bouitbir et al.26 | n = 34 male rats divided into 4 groups | Atorvastatin (10 mg/kg/day; n = 18) or placebo for 2 weeks | Treadmill (40'; 40 cm/s with increase of 5 cm/s up to exhaustion; 1 session) | Increase in ROS and decrease in mitochondrial respiration |
| Wu et al.48 | n = 10 subjects (5♂ and 5♀; 35-69 years) | Different types and doses of statins for 4 weeks | Plantar flexion (40% ML) for 7' or up to exhaustion | Increase in time of metabolic recovery and CK maintenance |
| Hubal et al.49 | n = 14 users of statins (n = 9 symptomatic; n = 6 asymptomatic) | Simvastatin or Atorvastatin (10-80 mg) up to myalgia onset (2 weeks to 4 months) | Sitting down and getting up from a chair 300 times or up to exhaustion | Decrease in the expression of oxidative phosphorylation genes and of mitochondrial proteins in symptomatic individuals |
| Meador and Huey50 | n = 59 mice divided in 6 groups | Cerivastatin (1 mg/kg/day) or saline solution (days 15-28) | Running wheels (adapted: days 1-28; non-adapted: days 15-28) | Adaptation to exercise prevented loss of strength and increased fatigue associated with statin |
| Bouitbir et al.25 | n = 20 male rats (trained, n = 10; sedentary, n = 10) | Atorvastatin application (4, 10, 40, 100, 200 and 400 µM) to the plantaris muscle | Treadmill (30'; 40 cm/s; 15% incline) for 10 days | Increased mitochondrial tolerance to the drug and decrease in production of free radicals |
CK: creatine kinase; HRmax: Maximum heart rate; MF: maximum force; CK-MB: cardiac creatine kinase; EC: eccentric contractions; UPS ubiquitin proteasome; ML: maximum load; MS: metabolic syndrome; rHR: resting heart rate; LM: lean mass; MR: maximal repetition; ROS: Reactive Oxygen Species.