Three patients with McArdle's disease exercised for 2 h at 30% VO2max. During exercise two phases occurred. During the first 15 min they experienced progressive fatigue and weakness of exercised muscles, with a rapid and complete recovery (adaptation phase). Following this, all 3 patients were able to continue exercise without difficulty ('second wind' phase). During the adaptation phase, patients have to cope with their inability to use muscle glycogen as a fuel. Processes occurring during this phase are as follows. An increase in cardiac output. This might be expected to increase muscle blood flow in order to supply exercising muscle with substrates that can substitute for muscle glycogen (free fatty acids (FFA), bloodborne glucose). Changes in the metabolic pathways. These cause a sufficient amount of hexose phosphates to be present to overcome the first 2.5 min of exercise, and FFA and bloodborne glucose to play a major role in energy supply at an earlier stage in exercise than in control subjects. An increase in EMG activity. This is most probably caused by the recruitment of more motor units to compensate for a failure of force generation in the muscle fibres. Central command seems to play an important role in the regulation of cardiovascular processes during the adaptation phase. Despite these compensatory mechanisms, metabolic stress occurs during the adaptation phase. During the 'second wind' phase there are no important differences between the metabolism of exercising muscle of patients with McArdle's disease and that of control subjects.

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Gut microbiota alterations in Parkinson’s disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.