Mayo Clinic Proceedings Home

Effects of Statin Therapy on Exercise Levels in Participants in the National Runners' and Walkers' Health Study



      To determine whether decreases in exercise 1) were greater in individuals who were diagnosed as having hypercholesterolemia than in those without the diagnosis during follow-up and 2) were greater in incident hypercholesterolemic participants starting statins than in those not treated with cholesterol-lowering medications.

      Participants and Methods

      Regression analyses of changes since baseline (Δ) in exercise vs diagnosis of hypercholesterolemia and its treatment in 66,377 runners and 12,031 walkers not using cholesterol medications at baseline who were resurveyed during the National Runners' and Walkers' Health Study follow-up (January 1, 1991, through December 31, 2006).


      A total of 3510 runners began statin treatment, 1779 began other or unspecified cholesterol-lowering drug treatment, and 2583 had untreated hypercholesterolemia; 58,505 runners remained nonhypercholesterolemic controls during the mean 7.2-year follow-up. Usual distance run decreased significantly more in hypercholesterolemic runners who began taking statins (mean ± SE: −0.47±0.06 km/d) than in runners who remained nonhypercholesterolemic during follow-up (−0.08±0.02 km/d) (P<.001). However, running distance also decreased significantly more in hypercholesterolemic runners who began unspecified/other (−0.52±0.08 km/d) or no (−0.47±0.07 km/d) cholesterol drugs than in nonhypercholesterolemic runners during follow-up. Moreover, Δrunning distance did not differ significantly between hypercholesterolemic runners who were statin treated vs those treated with other/unspecified (P=.64) or no (P=.94) cholesterol drugs. Initiating statin therapy was not associated with Δrunning pace in hypercholesterolemic runners or Δwalking distances in hypercholesterolemic walkers.


      These results are consistent with the premise that a decrease in running distance is associated with hypercholesterolemia and do not suggest that statins reduce exercise level or intensity.

      Abbreviations and Acronyms:

      Δ (difference between baseline and follow-up), BMI (body mass index), CK (creatine kinase), LDL-C (low-density lipoprotein cholesterol), MET-h/d (metabolic equivalents-hours per day), VO2max (maximum oxygen consumption)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Thompson P.D.
        • Clarkson P.
        • Karas R.H.
        Statin-associated myopathy.
        JAMA. 2003; 289: 1681-1690
        • Auer J.
        • Sinzinger H.
        • Franklin B.
        • Berent R.
        Muscle- and skeletal-related side-effects of statins: tip of the iceberg [published online September 17, 2014]?.
        Eur J Prev Cardiol. 2014;
        • Murlasits Z.
        • Radák Z.
        The effects of statin medications on aerobic exercise capacity and training adaptations.
        Sports Med. 2014; 44: 1519-1530
        • Sirvent P.
        • Fabre O.
        • Bordenave S.
        • et al.
        Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins.
        Toxicol Appl Pharmacol. 2012; 259: 263-268
        • Schick B.A.
        • Laaksonen R.
        • Frohlich J.J.
        • et al.
        Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin.
        Clin Pharmacol Ther. 2007; 81: 650-653
        • Stringer H.A.
        • Sohi G.K.
        • Maguire J.A.
        • Cote H.C.
        Decreased skeletal muscle mitochondrial DNA in patients with statin-induced myopathy.
        J Neurol Sci. 2013; 325: 142-147
        • Lee D.S.
        • Markwardt S.
        • Goeres L.
        • et al.
        Statins and physical activity in older men: the osteoporotic fractures in men study.
        JAMA Intern Med. 2014; 174: 1263-1270
        • Ganga H.V.
        • Slim H.B.
        • Thompson P.D.
        A systematic review of statin-induced muscle problems in clinical trials.
        Am Heart J. 2014; 168: 6-15
        • Kashani A.
        • Phillips C.O.
        • Foody J.M.
        • et al.
        Risks associated with statin therapy: a systematic overview of randomized clinical trials.
        Circulation. 2006; 114: 2788-2797
        • Panza G.A.
        • Taylor B.A.
        • Roman W.
        • Thompson P.D.
        Changes in muscle strength in patients with statin myalgia.
        Am J Cardiol. 2014; 114: 1215-1216
        • Parker B.A.
        • Capizzi J.A.
        • Grimaldi A.S.
        • et al.
        The effect of statins on skeletal muscle function.
        Circulation. 2013; 127: 96-103
        • Ballard K.D.
        • Parker B.A.
        • Capizzi J.A.
        • et al.
        Increases in creatine kinase with atorvastatin treatment are not associated with decreases in muscular performance.
        Atherosclerosis. 2013; 230: 121-124
        • Williams P.T.
        Vigorous exercise, fitness and incident hypertension, high cholesterol, and diabetes.
        Med Sci Sports Exerc. 2008; 40: 998-1006
        • Williams P.T.
        • Thompson P.D.
        Walking versus running for hypertension, cholesterol, and diabetes mellitus risk reduction.
        Arterioscler Thromb Vasc Biol. 2013; 33: 1085-1091
        • Williams P.T.
        Incident hypercholesterolemia in relation to changes in vigorous physical activity.
        Med Sci Sports Exerc. 2009; 41: 74-80
        • Williams P.T.
        • Franklin B.
        Vigorous exercise and diabetic, hypertensive, and hypercholesterolemia medication use.
        Med Sci Sports Exerc. 2007; 39: 1933-1941
        • Williams P.T.
        Relationship of distance run per week to coronary heart disease risk factors in 8283 male runners: the National Runners' Health Study.
        Arch Intern Med. 1997; 157: 191-198
        • Williams P.T.
        Non-exchangeability of running vs. other exercise in their association with adiposity, and its implications for public health recommendations.
        PLoS One. 2012; 7: e36360
        • Williams P.T.
        Advantage of distance- versus time-based estimates of walking in predicting adiposity.
        Med Sci Sports Exerc. 2012; 44: 1728-1737
        • Balke B.
        • Ware R.W.
        An experimental study of physical fitness of Air Force personnel.
        U S Armed Forces Med J. 1959; 10: 875-888
        • Hellerstein H.K.
        Limitations of marathon running in the rehabilitation of coronary patients: anatomic and physiologic determinants.
        Ann N Y Acad Sci. 1977; 301: 484-494
        • Cooper K.H.
        A means of assessing maximal oxygen intake: correlation between field and treadmill testing.
        JAMA. 1968; 203: 201-204
        • Terpak K.
        • Guthrie S.
        • Erickson S.
        Statin use and self-reported swimming performance in US masters swimmers.
        J Sports Sci. 2015; 33: 1-7
        • Traustadottir T.
        • Stock A.A.
        • Harman S.M.
        High-dose statin use does not impair aerobic capacity or skeletal muscle function in older adults.
        Age (Dordr). 2008; 30: 283-291
        • Golomb B.A.
        Statins and activity, proceed with caution.
        JAMA Intern Med. 2014; 174: 1270-1272
        • Eckel R.H.
        • Jakicic J.M.
        • Ard J.D.
        • et al.
        2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 63: 2960-2984
        • Williams P.T.
        • Krauss R.M.
        • Wood P.D.
        • Lindgren F.T.
        • Giotas C.
        • Vranizan K.M.
        Lipoprotein subfractions of runners and sedentary men.
        Metabolism. 1986; 35: 45-52
        • Mikus C.R.
        • Boyle L.J.
        • Borengasser S.J.
        • et al.
        Simvastatin impairs exercise training adaptations.
        J Am Coll Cardiol. 2013; 62: 709-714
        • Muraki A.
        • Miyashita K.
        • Mitsuishi M.
        • Tamaki M.
        • Tanaka K.
        • Itoh H.
        Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance.
        J Appl Physiol (1985). 2012; 113: 479-486
        • Bouitbir J.
        • Charles A.L.
        • Rasseneur L.
        • et al.
        Atorvastatin treatment reduces exercise capacities in rats: involvement of mitochondrial impairments and oxidative stress.
        J Appl Physiol. 2011; 111: 1477-1483
        • Coen P.M.
        • Flynn M.G.
        • Markofski M.M.
        • Pence B.D.
        • Hannemann R.E.
        Adding exercise training to rosuvastatin treatment: influence on serum lipids and biomarkers of muscle and liver damage.
        Metabolism. 2009; 58: 1030-1038
        • Rengo J.L.
        • Savage P.D.
        • Toth M.J.
        • Ades P.A.
        Statin therapy does not attenuate exercise training response in cardiac rehabilitation.
        J Am Coll Cardiol. 2014; 63: 2050-2051
        • Schachter M.
        Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update.
        Fundam Clin Pharmacol. 2005; 19: 117-125
        • Päivä H.
        • Thelen K.M.
        • Van Coster R.
        • et al.
        High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial.
        Clin Pharmacol Ther. 2005; 78: 60-68
        • Bruckert E.
        • Hayem G.
        • Dejager S.
        • Yau C.
        • Bégaud B.
        Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients: the PRIMO study.
        Cardiovasc Drugs Ther. 2005; 19: 403-414
        • Bouitbir J.
        • Daussin F.
        • Charles A.L.
        • et al.
        Mitochondria of trained skeletal muscle are protected from deleterious effects of statins.
        Muscle Nerve. 2012; 46: 367-373
        • Schaefer W.H.
        • Lawrence J.W.
        • Loughlin A.F.
        • et al.
        Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats.
        Toxicol Appl Pharmacol. 2004; 194: 10-23
        • Westwood F.R.
        • Bigley A.
        • Randall K.
        • Marsden A.M.
        • Scott R.C.
        Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity.
        Toxicol Pathol. 2005; 33: 246-257
        • Meador B.M.
        • Huey K.A.
        Statin-associated changes in skeletal muscle function and stress response after novel or accustomed exercise.
        Muscle Nerve. 2011; 44: 882-889
        • Kumar A.
        • Vashist A.
        • Kumar P.
        • Kalonia H.
        • Mishra J.
        Protective effect of HMG CoA reductase inhibitors against running wheel activity induced fatigue, anxiety like behavior, oxidative stress and mitochondrial dysfunction in mice.
        Pharmacol Rep. 2012; 64: 1326-1336
        • Sinzinger H.
        • O'Grady J.
        Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems.
        Br J Clin Pharmacol. 2004; 57: 525-528
        • Margetts B.
        • Vorster H.
        • Venter C.
        Evidence-based nutrition: the impact of information and selection bias on the interpretation of individual studies.
        South Afr J Clin Nutr. 2003; 16: 78-87
        • Loftus E.
        • Smith K.
        • Klinger M.
        • Fiedler J.
        Memory and mismemory for health events.
        in: Tanur J.M. Questions About Questions: Inquiries Into the Cognitive Bases of Surveys. Russell Sage Foundation, New York, NY1991: 102-137