erbated by statin therapy leading to the muscle complaints.
There was no apparent change in the onset of lactate
accumulation or “anaerobic threshold” during the exercise
test, however, which argues against an alteration in exercise
fat metabolism with statin treatment. One additional study
of 195 noninsulin diabetic patients noted a 6% increase in
resting RER (0.78 to 0.83), which the authors attributed to
improved glucose metabolism with statin treatment, but
exercise parameters were not measured in that study (42).
Consequently, these exercise results raise the possibility of
mitochondrial dysfunction during exercise, a problem that
could relate to CoQ10 depletion.
In contrast to these studies suggesting a mitochondrial
problem in statin myopathy (13,21–23,41–48), muscle biopsies
from 18 patients with statin-associated myopathy found
only 2 patients with decreased intramuscular levels of CoQ10
and some morphologic evidence of mitochondrial dysfunction
(36). Muscle biopsies from these patients revealed the
presence of a few ragged red fibers or cytochrome c
oxidase-negative fibers. It is not clear whether these
changes were produced by the depletion of CoQ10 or were
related to aging, given that both patients were older than 60
years old. In addition, the activity of complex III of the
mitochondrial respiratory chain, which is dependent on
CoQ10 activity, was normal in all participants.
Others have directly measured concentrations of high
energy phosphates, including adenosine triphosphate and
creatine phosphate, in the skeletal muscle of statin-treated
patients and found no changes despite 6 months of treatment
with 20 mg/day of simvastatin, suggesting that energy
supply to the muscle was not compromised (18). These
studies were performed at rest, however, and more subtle
differences may be obvious with exercise or during exercise
recovery.
erbated by statin therapy leading to the muscle complaints.There was no apparent change in the onset of lactateaccumulation or “anaerobic threshold” during the exercisetest, however, which argues against an alteration in exercisefat metabolism with statin treatment. One additional studyof 195 noninsulin diabetic patients noted a 6% increase inresting RER (0.78 to 0.83), which the authors attributed toimproved glucose metabolism with statin treatment, butexercise parameters were not measured in that study (42).Consequently, these exercise results raise the possibility ofmitochondrial dysfunction during exercise, a problem thatcould relate to CoQ10 depletion.In contrast to these studies suggesting a mitochondrialproblem in statin myopathy (13,21–23,41–48), muscle biopsiesfrom 18 patients with statin-associated myopathy foundonly 2 patients with decreased intramuscular levels of CoQ10and some morphologic evidence of mitochondrial dysfunction(36). Muscle biopsies from these patients revealed thepresence of a few ragged red fibers or cytochrome coxidase-negative fibers. It is not clear whether thesechanges were produced by the depletion of CoQ10 or wererelated to aging, given that both patients were older than 60years old. In addition, the activity of complex III of themitochondrial respiratory chain, which is dependent onCoQ10 activity, was normal in all participants.Others have directly measured concentrations of highenergy phosphates, including adenosine triphosphate andcreatine phosphate, in the skeletal muscle of statin-treatedpatients and found no changes despite 6 months of treatmentwith 20 mg/day of simvastatin, suggesting that energysupply to the muscle was not compromised (18). Thesestudies were performed at rest, however, and more subtledifferences may be obvious with exercise or during exerciserecovery.
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