Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders.
Mitochondrial disorders share common cellular consequences: (1) decreased ATP production; (2) increased reliance on alternative anaerobic energy sources; and (3) increased production of reactive oxygen species. The purpose of the present study was to determine the effect of a combination therapy (creatine monohydrate, coenzyme Q(10), and lipoic acid to target the above-mentioned cellular consequences) on several outcome variables using a randomized, double-blind, placebo-controlled, crossover study design in patients with mitochondrial cytopathies. Three patients had mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), four had mitochondrial DNA deletions (three patients with chronic progressive external ophthalmoplegia and one with Kearns-Sayre syndrome), and nine had a variety of other mitochondrial diseases not falling into the two former groups. The combination therapy resulted in lower resting plasma lactate and urinary 8-isoprostanes, as well as attenuation of the decline in peak ankle dorsiflexion strength in all patient groups, whereas higher fat-free mass was observed only in the MELAS group. Together, these results suggest that combination therapies targeting multiple final common pathways of mitochondrial dysfunction favorably influence surrogate markers of cellular energy dysfunction. Future studies with larger sample sizes in relatively homogeneous groups will be required to determine whether such combination therapies influence function and quality of life.
Rodriguez
M Christine
MC
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
MacDonald
Jay R
JR
Mahoney
Douglas J
DJ
Parise
Gianni
G
Beal
M Flint
MF
Tarnopolsky
Mark A
MA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects; D002648:Child; D003067:Coenzymes; D003401:Creatine / Q000378:metabolism / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood / Q000652:urine; D018592:Cross-Over Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008063:Thioctic Acid / Q000378:metabolism / Q000627:therapeutic use*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; C075750:8-epi-prostaglandin F2alpha; D008063:Thioctic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; D015237:Dinoprost; C024989:coenzyme Q10; D003849:Deoxyguanosine; D003401:Creatine