Statins reduce coenzyme Q10 and glucose tolerance in skeletal muscle

It's long been known that statins impair synthesis of the important metabolic cofactor and antioxidant coenzyme Q10 while inhibiting the production of cholesterol. Clinical research just published in the American Journal of Cardiology further confirms that the muscle pain and exercise intolerance experienced by many taking statins is caused at least in part by decreased CoQ10. The authors note:

"A prevalent side effect of statin therapy is muscle pain, and yet the basic mechanism behind it remains unknown. We hypothesize that a statin-induced reduction in muscle Q10 may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism."

They went about examining glucose tolerance and skeletal muscle coenzyme Q10 (Q10) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity in simvastatin-treated patients and well-matched control subjects by measuring plasma glucose and insulin during an oral glucose tolerance test. They also determined mitochondrial OXPHOS capacity with high-resolution respirometry, mitochondrial content and coenzyme Q10 levels. Their data certainly support the prudence of supplementing with CoQ10 when statins are given:

"Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q10 content was reduced, whereas mitochondrial content was similar between the groups. OXPHOS capacity was comparable between groups when complex I– and complex II–linked substrates were used alone, but when complex I + II–linked substrates were used (eliciting convergent electron input into the Q intersection [maximal ex vivo OXPHOS capacity]), a decreased capacity was observed in the patients compared with the control subjects."

The biological implications are striking:

"It may not be that surprising that a statin can produce an acute toxic effect in cells, but the fact that an impairment of function can be observed in human muscle fibers, obtained via a biopsy that is mechanically and chemically dissected and permeabilized, washed, and finally transferred to the respiration chamber, is truly remarkable. It shows that the impact of long-term treatment with the lipophilic statin simvastatin has profound functional (limitation of maximal OXPHOS capacity) and structural (decreased content of Q10, complex IV, antioxidant proteins, and UCP3) impact."

The weight of evidence argues in favor of CoQ10 supplementation and laboratory monitoring for increases in creatine kinase (CK) as a marker of muscle cell damage as a prudent standard of care. The authors conclude:

"In summary, we found that patients treated with simvastatin have impaired glucose tolerance compared with healthy control subjects. Furthermore, we found that skeletal muscle from patients treated long term with simvastatin displayed a decreased maximal OXPHOS capacity that may well be explained by a concomitant decrease in Q10 protein content without any changes in mitochondrial content. The result is a compromised energetic state within the skeletal muscle, possibly explaining side effects such as myalgia and exercise intolerance. Finally, we have reported that simvastatin-treated patients have an increased mitochondrial substrate sensitivity when complex I substrate was used, which is a true intrinsic mitochondrial event, and we hypothesize that this could be a compensatory mechanism for increased ROS production."