Metabolomics Patterns in Subjects with Multimorbidity: Implications for Free Carnitine and Medium-Chain Acylcarnitines as Predictors of Individual Fitness Adaptation

(1) Background: The MultiPill-Exercise study was an exercise-based lifestyle intervention program for subjects with more than one lifestyle-related disease. Metabolomics-based approaches are an emerging tool in sports medicine, both in basic science and in clinical contexts. In this explorative, hypothesis-generating study, we aimed at defining metabolite patterns in subjects with multimorbidity and to test the predictive value of metabolite patterns for fitness adaptation. (2) Methods: A targeted tandem mass spectrometry (MS) approach on dried spots of capillary blood was employed, analyzing n = 86 subjects. (3) Results: In response to an acute bout of exhaustive exercise, aromatic amino acids (AA) tyrosine (Tyr) and phenylalanine (Phe), total carnitine (Cx) and short- as well as medium-chain acylcarnitines (SCA and MCA) were upregulated. Furthermore, concentrations of most metabolites were higher in males. Multiple regression defined free carnitine (C0), MCA and MCA_Delta, i.e. changes in concentrations during acute exercise, as important predictors of intervention-associated fitness adaptation after six months, explaining 24.8% and 24.4% of absolute and relative power gains associated with a respiratory quotient (RQ) of 1, a submaximal fitness parameter. (4) Conclusions: Our data suggest utility of metabolomics data in subjects with multimorbidity, both in the context of basic research and clinical applications.