Statins

Mechanism of Action

• Hydroxy-methyl-glutaryl Coenzyme A (HMG-CoA) reductase inhibitors act by blocking the enzyme in liver responsible for making cholesterol, particularly low-density lipoprotein cholesterol (LDL-C) and triglycerides
• Also decrease other downstream products of the mevalonate pathway
  • Affecting inflammation, nitric oxide synthesis, the coagulation cascade, and other processes (Parker & Thompson 2012)

Treatment

• Hypercholesterolemia (high cholesterol)

Names

• Lovastatin (Advicor, Mevacor, Altoprev, Altocor)
• Rosuvastatin (Crestor)
• Simvastatin (Simcor, Zocor, Lipex, Vytorin)
• Fluvastatin (Lescol)
• Pravastatin (Pravachol, Selektine, Lipostat)
• Atorvastatin (Caduet, Lipitor, Torvast)
• Ezetimibe & Simvastatin (Vytorin)
• Sitagliptin & Simvastatin (Juvisync)
• Pitavastatin (Livalo, Pitava)
• Cerivastatin (Lipobay, Baycol)

Effect on Exercise and Rest

• No effect on resting heart rate
• Lower resting blood pressure (Bautista 2009)
• No effect of statin therapy on maximal oxygen uptake (VO2 max) (Parker & Thompson 2012)
• Increase of respiratory exchange ratio (RER = VCO2/VO2)
  • May suggest statins impair fat metabolism (Parker & Thompson 2012)
• No change in the onset of lactate accumulation or “anaerobic threshold” during the exercise test (Parker & Thompson 2012)
  • Argues against an alteration in exercise fat metabolism with statin treatment
• Muscle weakness
  • Reductions of 10–40% in hip abduction strength (Parker & Thompson 2012)
  • Other studies have shown no effects of high-dose statin therapy on handgrip, upper body, and leg muscle strength (Parker & Thompson 2012)
• Phosphocreatine (PCr) exercise recovery time following calf flexion exercise increased after a 4-weeks of statin therapy in 10 hypercholesterolemic patients (Parker & Thompson 2012)
  • Suggests statins impair mitochondrial oxidative function
• Statin related complaints are exacerbated by exercise
  • More muscle symptoms have been observed in physically active individuals than sedentary individuals (Parker & Thompson 2012)
  • Physically active individuals including athletes are less likely to tolerate statin therapy (Parker & Thompson 2012)
  • Statins increase exercise-related muscle injury (Parker & Thompson 2012)
  • Statins exacerbate CK release and presumably the skeletal muscle damage associated with eccentric exercise (Parker & Thompson 2012)
  • Susceptibility to exercise-induced muscle injury with statins does not appear to be dose-dependent but does increase with age (Parker & Thompson 2012)

Other Risks and Side Effects

• Polyneuropathy (Mercola 2010)
  • Nerve damage in hands and feet
• Acidosis (Mercola 2010)
• Immune depression (Mercola 2010)
• Diabetes or hyperglycemia (Mercola 2010. Shah & Goldfine AB 2012)
  • Increased insulin resistance
  • Increased blood sugar
    • Hyperglycemia from statins can be misdiagnosed as type 2 diabetes
• Liver Dysfunction (Mercola 2010)
• Anemia (Mercola 2010)
• Sexual Dysfunction (Mercola 2010)
• Cataracts (Mercola 2010)
• Memory Loss (Mercola 2010)
• Rhabdomyolysis with acute renal failure and even death
  • Overall reported incidence of fatal rhabdomyolysis of 1.5 deaths per 10,000,000 prescriptions (Parker & Thompson 2012)
• Muscular symptoms
  • Muscular issues include myalgia, cramps and weakness (Parker & Thompson 2012)
  • Myalgia during therapy with the more powerful statins has varied from 1% in pharmaceutical company reports to 25% of patients (Parker & Thompson 2012)
  • High dosages of statins: 11% developed muscle symptoms, 4% had symptoms severe enough to interfere with daily activities, and 0.4% were actually confined to bed with their symptoms (Parker & Thompson 2012)

Nutrition

• CoQ10
  • Low dose of CoQ10 (100 mg/day) has been shown to decrease pain severity by 40% and pain interference with daily activities by 38% (Parker & Thompson 2012)
  • In another study showed supplementing CoQ10 (200 mg/day) found no difference in myalgia score (Parker & Thompson 2012)
• Carbohydrate depletion during exercise could make type II glycolytic muscle fibers more susceptible to injury (Parker & Thompson 2012)
• There may be a link between Vitamin D insufficiency to statin myopathy (Parker & Thompson 2012)

Unknown Issues

• Parker & Thompson (2012) point out substantial gaps in the clinical knowledge with may unresolved issues.
  • One unknown issue is if physicians should discontinue statin use for their patients several days prior to endurance events
    • Especially if heat stress or other potential exacerbators of rhabdomyolysis may occur
    • Particularly important issue for older runners who appear more likely to experience muscle injury

Recommended Population

• 40 to 75 years old individuals with one or more risk factors for cardiovascular disease and who have a 10 percent or greater risk (US Preventive Services Task Force 2016)
  • US PSTF Guideline did not fully meet the IOM standards for commercial COI management (Jefferson & Pearson 2017)
    • Suggests guidelines could have been tainted by a conflict of interest

Populations not recommended

• Athletes
• Pregnant Women (Mercola 2010)

Banned Status

• None

References

Jefferson AA, Pearson SD (2017). Conflict of Interest in Seminal Hepatitis C Virus and Cholesterol Management Guidelines. JAMA Intern Med. 2017;177(3):352-357.

Bautista LE (2009). Blood pressure-lowering effects of statins: who benefits? J Hypertens. 27(7):1478-84.

Parker BA, Thompson PD (2012). Effect of Statins on Skeletal Muscle: Exercise, Myopathy, and Muscle Outcomes. Exerc Sport Sci Rev. 40(4): 188–194.

Mercola J, Ravnskov U, Cohen J (2010). Do You Take Any of These 11 Dangerous Statins or Cholesterol Drugs? Mercola.com, Accessed 12 Nov 2017.

Shah RV, Goldfine AB (2012) Statins and Risk of New-Onset Diabetes Mellitus. Circulation;126:e282-e284 ahajournals.org. Accessed 22 Nov 2017

US Preventive Services Task Force (2016) Final Recommendation Statement Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Preventive Medication. uspreventiveservicestaskforce.org, Accessed 12 Nov 2017.