Effects of dichloroacetate on metabolism and endurance of human limb muscle

S. M. Poucher, C. L. Murrant, K. M. Krause, F. H. Andrade, R. Herrick, A. A. Taylor, P. W. Stacpoole, M. B. Reid

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Dichloroacetate (DCA) activates pyruvate dehydrogenase, stimulating aerobic metabolism of carbohydrate. DCA could promote aerobic metabolism during exercise thereby decreasing the changes of metabolites and potentially delaying the onset of fatigue. Methods. Eight healthy subjects undertook voluntary exercise of ankle plantarflexor muscles to exhaustion after intravenous infusion of either DCA (50 mg/kg) or volume-matched saline. Each subject depressed a foot pedal connected to a hydraulic-pneumatic ergometer; we used 21P-NMR to measure phosphorylated metabolites-ATP, phosphocreatine (PCr), inorganic phosphate (Pi) - and pH in gastrocnemius muscle, ergometer output was analyzed for timing, duty cycle, force output, and time to task failure Metabolic recovery was monitored for 15 mins after exhaustion. Results. Under control conditions, exercise caused intramuscular pH to fall in all subjects (avg 7.04 ± 0.01 SE to 6.48 ± 0.07); PCr also fell and Pi increased such that Pi:PCr increased > 40-fold (0.10 ± 0 01 to 4.87 ± 1.11); ATP profile did not change. Task failure occured after 291 ± 27 s Metabolites returned to control levels within the 15 mm recovery period. On average. DCA did not significantly alter muscle metabolism during exercise or recovery; nor was time-to-task failure significantly increased (364±47 s). In two subjects, however, DCA doubled endurance time and muscle pH remained elevated during exercise; this pH stability was not seen in control trials on the same subjects or in trials on other subjects (46 trials total). Conclusion. In general, DCA does not improve endurance or alter the metabolic response of muscle to fatiguing exercise. Limited observations suggest, however, that DCA may inhibit acidosis and increase endurance in a subpopulation of individuals.

Original languageEnglish
Pages (from-to)A12
JournalFASEB Journal
Issue number3
StatePublished - 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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