Ascorbate attenuates cycling exercise-induced neuromuscular fatigue but fails to improve exertional dyspnea and exercise tolerance in COPD.

We examined the effect of intravenous ascorbate administration (VitC) on exercise-induced redox balance, inflammation, exertional dyspnea, neuromuscular fatigue, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Eight COPD patients completed constant-load cycling (~80% of peak power output, 83±10W) to task-failure following intravenous VitC (2g) or saline (placebo, PL) infusion. All participants repeated the shorter of the two exercise trials (isotime), with the other infusate. Quadriceps fatigue was determined by pre- to post-exercise changes in quadriceps twitch-torque (∆Qtw, electrical femoral nerve stimulation). Corticospinal excitability before, during, and after exercise was assessed by changes in motor-evoked potentials triggered by transcranial magnetic stimulation. VitC increased superoxide dismutase (marker for endogenous antioxidant capacity) by 129% and mitigated C-reactive protein (marker for inflammation) in the plasma during exercise, but failed to alter the exercise-induced increase in lipid peroxidation (malondialdehyde) and free radicals (EPR-spectroscopy). While VitC did, indeed, decrease neuromuscular fatigue (∆Qtw PL: -29±5%, VitC: -23±6%, P 0.3). Thus, although VitC facilitated indicators for antioxidant capacity, diminished inflammatory markers, and improved neuromuscular fatigue resistance, it failed to improve exertional dyspnea and cycling exercise tolerance in patients with COPD. As dyspnea is recognized to limit exercise tolerance in COPD, the otherwise beneficial effects of VitC may have been impacted by this unaltered sensation.