Reactive oxygen species (ROS) have been linked with both depressed Na + ,K + -pump activity and skeletal muscle fatigue. This study investigated N -acetylcysteine (NAC) effects on muscle Na + ,K + -pump activity and potassium (K + ) regulation during prolonged, submaximal endurance exercise. Eight well-trained subjects participated in a double-blind, randomised, crossover design, receiving either NAC or saline (CON) intravenous infusion at 125 mg kgfor 15 min, then 25 mg kg −1 h −1 for 20 min prior to and throughout exercise. Subjects cycled for 45 min at 71%V O 2 peak , then continued at 92%V O 2 peak until fatigue. Vastus lateralis muscle biopsies were taken before exercise, at 45 min and fatigue and analysed for maximal in vitro Na + ,K + -pump activity (K + -stimulated 3-O-methyfluorescein phosphatase; 3-O-MFPase). Arterialized venous blood was sampled throughout exercise and analysed for plasma K + and other electrolytes. Time to fatigue at 92%V O 2 peak was reproducible in preliminary trials (C.V. 5.6 ± 0.6%) and was prolonged with NAC by 23.8 ± 8.3% (NAC 6.3 ± 0.5 versus CON 5.2 ± 0.6 min, P < 0.05). Maximal 3-O-MFPase activity decreased from rest by 21.6 ± 2.8% at 45 min and by 23.9 ± 2.3% at fatigue (P < 0.05). NAC attenuated the percentage decline in maximal 3-O-MFPase activity (%Δactivity) at 45 min (P < 0.05) but not at fatigue. When expressed relative to work done, the %Δactivity-to-work ratio was attenuated by NAC at 45 min and fatigue (P < 0.005). The rise in plasma [K + ] during exercise and the Δ[K + ]-to-work ratio at fatigue were attenuated by NAC (P < 0.05). These results confirm that the antioxidant NAC attenuates muscle fatigue, in part via improved K + regulation, and point to a role for ROS in muscle fatigue.

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine, and glutathione and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min vs. Con 5.3 +/- 0.7 min; P <0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P <0.005). Muscle cysteine and cystine were unchanged during Con, but were elevated above preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05). Neither exercise nor NAC affected whole blood TGSH. Whereas blood GSH was decreased and calculated oxidized glutathione increased with exercise (P <0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.

A recovery placebo administered after an acute high-intensity interval training session is superior in the recovery of muscle strength over 48 h as compared with TWI and is as effective as CWI. This can be attributed to improved ratings of readiness for exercise, pain, and vigor, suggesting that the commonly hypothesized physiological benefits surrounding CWI are at least partly placebo related.

Characterization of expression of, and consequently also the acute exercise effects on, Na + ,K + -ATPase isoforms in human skeletal muscle remains incomplete and was therefore investigated. Fifteen healthy subjects (eight males, seven females) performed fatiguing, knee extensor exercise at ∼40% of their maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue and 3 and 24 h postexercise, and analysed for Na + ,K + -ATPase α 1 , α 2 , α 3 , β 1 , β 2 and β 3 mRNA and crude homogenate protein expression, using Real-Time RT-PCR and immunoblotting, respectively. Each individual expressed gene transcripts and protein bands for each Na + ,K + -ATPase isoform. Each isoform was also expressed in a primary human skeletal muscle cell culture. Intense exercise (352 ± 69 s; mean ± S.E.M.) immediately increased α 3 and β 2 mRNA by 2.4-and 1.7-fold, respectively (P < 0.05), whilst α 1 and α 2 mRNA were increased by 2.5-and 3.5-fold at 24 h and 3 h postexercise, respectively (P < 0.05). No significant change occurred for β 1 and β 3 mRNA, reflecting variable time-dependent responses. When the average postexercise value was contrasted to rest, mRNA increased for α 1 , α 2 , α 3 , β 1 , β 2 and β 3 isoforms, by 1.4-, 2.2-, 1.4-, 1.1-, 1.0-and 1.0-fold, respectively (P < 0.05). However, exercise did not alter the protein abundance of the α 1 -α 3 and β 1 -β 3 isoforms. Thus, human skeletal muscle expresses each of the Na + ,K + -ATPase α 1 , α 2 , α 3 , β 1 , β 2 and β 3 isoforms, evidenced at both transcription and protein levels. Whilst brief exercise increased Na + ,K + -ATPase isoform mRNA expression, there was no effect on isoform protein expression, suggesting that the exercise challenge was insufficient for muscle Na + ,K + -ATPase up-regulation.

This study examined the effects of supplemental beta-hydroxy-beta-methylbutyrate (HMB) on muscle damage as a result of intense endurance exercise. Subjects (n = 13) were paired according to their 2-mile run times and past running experience. Each pair was randomly assigned a treatment of either HMB (3 g/day) or a placebo. After 6 wk of daily training and supplementation, all subjects participated in a prolonged run (20-km course). Creatine phosphokinase and lactate dehydrogenase (LDH) activities were measured before and after a prolonged run to assess muscle damage. The placebo-supplemented group exhibited a significantly greater (treatment main effect, P = 0.05) increase in creatine phosphokinase activity after a prolonged run than did the HMB-supplemented group. In addition, LDH activity was significantly lower (treatment main effect, P = 0.003) with HMB supplementation compared with the placebo-supplemented group. In conclusion, supplementation with 3.0 g of HMB results in a decreased creatine phosphokinase and LDH response after a prolonged run. These findings support the hypothesis that HMB supplementation helps prevent exercise-induced muscle damage.