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Dichloroacetate Therapy Attenuates the Blood Lactate Response to Submaximal Exercise in Patients with Defects in Mitochondrial Energy Metabolism

Department of Epidemiology, Nutritional Sciences Program, University of Washington (G.E.D.), Seattle, Washington 98195; and Departments of Medicine (L.A.P., P.W.S.), Pediatrics (R.E.N.), and Biochemistry and Molecular Biology (P.W.S.), and General Clinical Research Center (D.W.T.), University of Florida, Gainesville, Florida 32610

Address all correspondence and requests for reprints to: Dr. G. E. Duncan, 305 Raitt Hall, Box 353410, University of Washington, Seattle, Washington 98195. E-mail: duncag{at}u.washington.edu.

We determined acute and chronic effects of dichloroacetate (DCA) on maximal (MAX) and submaximal (SUB) exercise responses in patients with abnormal mitochondrial energetics. Subjects (n = 9) completed a MAX treadmill bout 1 h after ingesting 25 mg/kg DCA or placebo (PL). A 15-min SUB bout was completed the next day while receiving the same treatment. After a 1-d washout, MAX and SUB were repeated while receiving the alternate treatment (acute). Gas exchange and heart rate were measured throughout all tests. Blood lactate (Bla) was measured 0, 3, and 10 min after MAX, and 5, 10, and 15 min during SUB. MAX and SUB were repeated after 3 months of daily DCA or PL. After a 2-wk washout, a final MAX and SUB were completed after 3 months of alternate treatment (chronic). Average Bla during SUB was lower (P < 0.05) during both acute (1.99 ± 1.10 vs. 2.49 ± 1.52 mmol/liter) and chronic (1.71 ± 1.37 vs. 2.39 ± 1.32 mmol/liter) DCA vs. PL despite similar exercise intensities between conditions (75 and 70% maximal exercise capacity during acute and chronic treatment). Thus, although DCA does not alter MAX responses, acute and chronic DCA attenuate the Bla response to moderate exercise in patients with abnormal mitochondrial energetics.

This work was supported by American Heart Association Grant 9920174V and NIH Grants ES-07355 and RR-00082.

Abbreviations: Bla, Blood lactate; DCA, dichloroacetate; HR, heart rate; MAX, maximal; NCV, nerve conduction velocity; PDC, pyruvate dehydrogenase complex; PL, placebo; RPE, rating of perceived exertion scale; SUB, submaximal; VO_2peak, maximal exercise capacity.