Effects of endurance training on skeletal muscle mitochondrial function in Huntington disease patients.

BACKGROUND: Mitochondrial dysfunction may represent a pathogenic factor in Huntington disease (HD). Physical exercise leads to enhanced mitochondrial function in healthy participants. However, data on effects of physical exercise on HD skeletal muscle remains scarce. We aimed at investigating adaptations of the skeletal muscle mitochondria to endurance training in HD patients. METHODS: Thirteen HD patients and 11 healthy controls completed 26 weeks of endurance training. Before and after the training phase muscle biopsies were obtained from M. vastus lateralis. Mitochondrial respiratory chain complex activities, mitochondrial respiratory capacity, capillarization, and muscle fiber type distribution were determined from muscle samples. RESULTS: Citrate synthase activity increased during the training intervention in the whole cohort (P = 0.006). There was no group x time interaction for citrate synthase activity during the training intervention (P = 0.522). Complex III (P = 0.008), Complex V (P = 0.043), and succinate cytochrome c reductase (P = 0.008) activities increased in HD patients and controls by endurance training. An increase in mass-specific mitochondrial respiratory capacity was present in HD patients during the endurance training intervention. Overall capillary-to-fiber ratio increased in HD patients by 8.4% and in healthy controls by 6.4% during the endurance training intervention. CONCLUSIONS: Skeletal muscle mitochondria of HD patients are equally responsive to an endurance-training stimulus as in healthy controls. Endurance training is a safe and feasible option to enhance indices of energy metabolism in skeletal muscle of HD patients and may represent a potential therapeutic approach to delay the onset and/or progression of muscular dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT01879267 . Registered May 24, 2012.

Altered skeletal muscle (mitochondrial) properties in patients with mitochondrial DNA single deletion myopathy.

BACKGROUND: Mitochondrial myopathy severely affects skeletal muscle structure and function resulting in defective oxidative phosphorylation. However, the major pathomechanisms and therewith effective treatment approaches remain elusive. Therefore, the aim of the present study was to investigate disease-related impairments in skeletal muscle properties in patients with mitochondrial myopathy. Accordingly, skeletal muscle biopsies were obtained from six patients with moleculargenetically diagnosed mitochondrial myopathy (one male and five females, 53 ± 9 years) and eight age- and gender-matched healthy controls (two males and six females, 58 ± 14 years) to determine mitochondrial respiratory capacity of complex I-V, mitochondrial volume density and fiber type distribution. RESULTS: Mitochondrial volume density (4.0 ± 0.5 vs. 5.1 ± 0.8 %) as well as respiratory capacity of complex I-V were lower (P < 0.05) in mitochondrial myopathy and associated with a higher (P < 0.001) proportion of type II fibers (65.2 ± 3.6 vs. 44.3 ± 5.9 %). Additionally, mitochondrial volume density and maximal oxidative phosphorylation capacity correlated positively (P < 0.05) to peak oxygen uptake. CONCLUSION: Mitochondrial myopathy leads to impaired mitochondrial quantity and quality and a shift towards a more glycolytic skeletal muscle phenotype.

Multiday acute sodium bicarbonate intake improves endurance capacity and reduces acidosis in men.

BACKGROUND: The purpose was to investigate the effects of one dose of NaHCO3 per day for five consecutive days on cycling time-to-exhaustion (Tlim) at 'Critical Power' (CP) and acid-base parameters in endurance athletes. METHODS: Eight trained male cyclists and triathletes completed two exercise periods in a randomized, placebo-controlled, double-blind interventional crossover investigation. Before each period, CP was determined. Afterwards, participants completed five constant-load cycling trials at CP until volitional exhaustion on five consecutive days, either after a dose of NaHCO3 (0.3 g·kg-1 body mass) or placebo (0.045 g·kg-1 body mass NaCl). RESULTS: Average Tlim increased by 23.5% with NaHCO3 supplementation as compared to placebo (826.5 ± 180.1 vs. 669.0 ± 167.2 s; P = 0.001). However, there was no time effect for Tlim (P = 0.375). [HCO3-] showed a main effect for condition (NaHCO3: 32.5 ± 2.2 mmol·l-1; placebo: 26.2 ± 1.4 mmol·l-1; P < 0.001) but not for time (P = 0.835). NaHCO3 supplementation resulted in an expansion of plasma volume relative to placebo (P = 0.003). CONCLUSIONS: The increase in Tlim was accompanied by an increase in [HCO3-], suggesting that acidosis might be a limiting factor for exercise at CP. Prolonged NaHCO3 supplementation did not lead to a further increase in [HCO3-] due to the concurrent elevation in plasma volume. This may explain why Tlim remained unaltered despite the prolonged NaHCO3 supplementation period. Ingestion of one single NaHCO3 dose per day before the competition during multiday competitions or tournaments might be a valuable strategy for performance enhancement. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov Identifier NCT01621074.