Background and AimsHealthy dietary patterns and exercise practices have been associated with improved metabolic and inflammatory profiles. However, studies regarding the combined effect of these interventions on plasma biomarkers and metabolome in older adults are sparser. The primary aim of this study was to investigate the impact of a combined Mediterranean Diet-based Sustainable Healthy Diet (SHD) and Multicomponent Training (MT) intervention on the plasma biomarkers and metabolome and how dietary intake and exercise could modulate these effects. MethodsSHD intervention included a weekly supply of Mediterranean Diet-based SHD food and four nutrition sessions involving a Mediterranean-Diet culinary workshop, and the exercise program included 50-minute MT group sessions, held three times a week, lasting both 12 weeks. Plasma biomarkers were obtained through standard biochemical analysis. A proton (1H) nuclear magnetic resonance (NMR) spectroscopy-based metabolomics approach was used to study the metabolome in blood plasma. Repeated measures ANOVA were performed and adjusted for confounders. ResultsSHD+MT intervention significantly decreased HDL-C and calcium. SHD+MT showed some changes in common with the SHD and MT group, namely a significant decrease in citrate levels (p=0.009 for SHD+MT; p=0.037 for SHDT) and an increase in pyruvate (p<0.001 for MT and SHD+MT). The SHD+MT group also revealed specific changes in the levels of some amino acids (decrease in alanine, glutamine and lysine: p=0.026; p<0.001; p=0.038, respectively). Formate (p=0.025) and unsaturated lipids (p=0.011) increase are consistent with changes in energy, amino acid and lipoprotein metabolism. ConclusionOur data show that a combined lifestyle intervention program, including a Mediterranean Diet-based SHD and MT, could modulate biomarker and metabolome and there seems to be a metabolic path associated to these interventions in older adults. Due to its wide-ranging relevance, it is pertinent to assess to what extent combined SHD and MT can contribute to better clinical profiles.