Effects of Statins on Energy and Fatigue With Exertion: Results From a Randomized Controlled Trial

Study Questions:

Do statins increase symptoms of fatigue and decreased energy?


The randomized, controlled University of California, San Diego Statin Study, aimed to examine noncardiac outcomes with statin use. Subjects were randomized to one of three arms; 20 mg simvastatin, 40 mg pravastatin, or placebo for 6 months. Single-item self-ratings of change from baseline in “energy” and “fatigue with exertion” were used, assessed on 6-month follow-up, and rated (5-point scale) from “much less” (−2) to “much more” (+2) versus baseline. Energy and fatigue with exertion were rated at baseline from 0 (none) to 10 (maximum possible). All subjects rated energy; the final 397 subjects (a randomized subset) rated baseline fatigue with exertion.


A total of 1,016 subjects were enrolled in this study, with 397 subjects rating baseline fatigue with exertion. Energy and predictors for exertion fatigue were comparable at baseline between the groups. Exertional fatigue at baseline did differ among the groups. The mean on-treatment change in the combined variable (energy and fatigue on exertion) was significant for the statin arms. Women appeared to report the greatest changes. The balance of those reporting maximal worsening versus maximal improvement (“much worse” vs. baseline on each component vs. “much better” on each) was adversely shifted for statins versus placebo (p = 0.002), and for each statin separately (simvastatin, p = 0.03; pravastatin, p = 0.01).


The authors concluded that these data suggest that statin effect energy may lead to exertional fatigue; however, they acknowledge that these results are based on small numbers of subjects.


These findings warrant further investigations. Given the importance of regular physical activity to improve heart health, understanding the implications of changes in these symptoms is important.

Clinical Topics: Dyslipidemia, Nonstatins, Novel Agents, Statins

Keywords: Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Fatigue, Self Report, Pravastatin, Cardiovascular Diseases, Motor Activity, Health Status, Simvastatin

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