The MultiPill-Exercise study was an exercise-based intervention program for subjects with multiple lifestyle-related diseases, such as overweight and obesity. Metabolomics-based approaches are an emerging tool in sports medicine. This explorative, hypothesis-generating study aimed to define metabolite patterns in subjects with multimorbidity and to correlate them with subjects’ individual fitness adaptation. Prior to starting the intervention, spiroergometry to exhaustion was carried out, and capillary blood was drawn from subjects’ earlobes before and immediately after the test. Subsequently, a targeted tandem mass spectrometry approach on dried blood spots was employed, analyzing n = 86 subjects. Metabolite patterns were correlated with subjects’ fitness adaptation after six months. Aromatic amino acids tyrosine and phenylalanine, total carnitine and short- as well as medium-chain acylcarnitines were upregulated during spiroergometry. Multiple regression defined “at-rest” concentrations of free carnitine and medium-chain acylcarnitines, as well as changes in the latter during spiroergometry, as associated with subsequent fitness adaptation. These three parameters explained 24.8% and 24.4% of absolute and relative power gains associated with a respiratory quotient of 1, the latter being a submaximal fitness parameter. Our data suggest potential utility of metabolite patterns as indicators of trainability in subjects with multimorbidity. However, future studies should employ more standardized approaches, specifically with regard to patient subgroups, exercise intervention and diet/nutrition.
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Reul et al. (2026) studied this question.
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