Statins side effects can include fatigue and loss of tolerance to exertion
A randomized trial just published in the Archives of Internal Medicine offers important evidence that statins side effects can include fatigue, especially fatigue on exertion, for a significant percentage of patients. The authors state:
"...fatigue and exertional intolerance are adverse effects reported by patients receiving statins...Although many observational reports have cited fatigue and exertional fatigue with statin use, to our knowledge, no randomized trials have addressed this issue to date."
They designed their study to...
"...evaluate whether moderate-dose statins affected energy and exertional fatigue in a broadly sampled primary prevention population."
The randomized 1016 subjects (624 men and 324 women) equally to receive 20 mg of simvastatin, 40 mg of pravastatin, or a placebo in identical capsules for 6 months. The study subjects then rated themselves for changes from baseline in "energy" and "fatigue with exertion" and “EnergyFatigEx” values were generated by summing ratings for the energy and fatigue with exertion measures. What did the data show?
"Results of t tests of difference in mean on-treatment change in EnergyFatigEx were significant for combined statins vs placebo. Each statin contributed...Women were disproportionately affected...Adjusted for baseline EnergyFatigEx (via ordinal logit), effects on EnergyFatigEx were significantly unfavorable for combined statins and each statin separately...The balance of those reporting maximal worsening vs maximal improvement (“much worse” vs baseline on each component vs “much better” on each) was adversely shifted for statins vs placebo (P = .002) and for each statin separately (simvastatin, P = .03; pravastatin, P = .01)"
Not every patient will suffer these side effects of fatigue and exertional intolerance on a moderate dose of statins, nor was the natural statin red rice yeast included in this study, but clinicians should bear in mind the authors' comments:
"To our knowledge, this is the first randomized evidence affirming unfavorable statin effects on energy and exertional fatigue. Effects were seen in a generally healthy sample given modest statin doses, and both simvastatin and pravastatin contributed to the significant adverse effect of statins on energy and fatigue with exertion. Particularly for women, these unfavorable effects were not uncommon...These findings are important, given the central relevance of energy and functional status to well-being."
Practitioners should note:
"These effects, germane to quality of life, merit consideration when prescribing or contemplating use of statins, particularly in groups without expected net morbidity/mortality benefit, extending to “high-risk” primary prevention and women and elderly persons (including those with coronary artery disease)."
Moreover...
"Effects may take time to manifest...Thus, long-term trials are important, if statin use is to be recommended in younger individuals. Meanwhile, physicians should be alert to patients' reports of exertional fatigue or diminished energy during statin use."
It's well known that statins block the production of coenzyme Q10 while inhibiting cholesterol formation. This evidence implies that we should be investigating what other important pathways are blocked.