Abstract
PURPOSE To determine the acute and chronic effects of dichloroacetate (DCA) on maximal (MAX) and submaximal (SUB) exercise responses in patients with inborn errors of mitochondrial energetics. METHODS Patients (n=11) completed a MAX treadmill test ∼ 3.5 hr after ingesting 25 mg/kg DCA or placebo (PL). The following day, a 15 min SUB exercise bout (∼65% VO2peak) was completed while taking the same treatment. After a one-day washout period, MAX and SUB were repeated crossed-over to the other study treatment (acute phase). Gas exchange variables were measured continuously throughout all tests. Heart rate (HR), blood pressure (BP), blood lactate (LA), and ratings of perceived exertion (RPE) were obtained at 0, 3 and 10 min following MAX, and 5, 10 and 15 min during SUB. Both MAX and SUB were repeated after three months of daily DCA or PL. After a two-week washout period, patients switched to the alternate treatment for an additional three months and completed a final MAX and SUB (chronic phase). RESULTS There was a significant treatment effect for chronic DCA vs. PL for VO2peak (21.59 ±8.21 vs. 20.51 ±8.2 ml.min−1.kg−1.,p = 0.016). Average LA was lower (1.89 ±1.03 vs. 2.37 ±1.39 mmol/L,p = 0.009), but average HR was higher (129.0 ±12.7 vs. 123.8 ±12.6 b/min,p = 0.032), for DCA vs. PL during SUB during the acute phase. The overall mean LA level during SUB was significantly lower for DCA vs. PL (1.93 ±1.15 vs. 2.25 ±1.33 mmol/L,p = 0.019), regardless of testing period. This occurred despite exercising at similar workloads (73.3 ±10.5 vs. 69.1 ±8.3% VO2peak for DCA and PL). CONCLUSIONS Aerobic capacity is greater following chronic DCA compared to similar PL treatment. Furthermore, DCA reduces blood LA levels during SUB exercise. Thus, DCA treatment improves markers of MAX and SUB aerobic function in patients with inborn errors of mitochondrial energetics.
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