Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids.
Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.
Phillips
Paul S
PS
Scripps Mercy Clinical Research Center, Scripps Mercy Hospital, San Diego, CA 92103, USA. phillips.paul@scrippshealth.org
Ciaraldi
Theodore P
TP
Kim
Dong-Lim
DL
Verity
M Anthony
MA
Wolfson
Tanya
T
Henry
Robert R
RR
D000368:Aged; D001706:Biopsy; D002478:Cells, Cultured; D005080:Exercise Test; D005215:Fasting / Q000378:metabolism / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
D005227:Fatty Acids; D000960:Hypolipidemic Agents