Association of handgrip strength with the plasma metabolomic profile: secondary analysis of a protein intervention study

INTRODUCTION: There is interest in the potential impact of increased protein intake on muscle function in older adults. However, there is paucity of information on effects of different protein types. OBJECTIVES: To determine the impact of protein sources (plant vs dairy) on the plasma metabolomic profile, and to explore associations between metabolites and handgrip strength. METHODS: In this secondary analysis of a 12-week double-blinded RCT, 171 healthy adults (≥50 years) were assigned to high plant protein (23 g/d), high dairy protein (22 g/d) or low protein (2 g/d) supplement. Plasma samples were collected pre- and post-intervention and analysed using a targeted LC-MS platform. Main and interaction effects were estimated using ANOVA-simultaneous component analysis (ASCA). Spearman correlation analysis evaluated associations between metabolites and handgrip strength, with false discovery rate correction (q < 0.05). RESULTS: ASCA revealed no significant main effect of group (p = 0.23) or group × time interaction (p = 1.00), while time had a significant effect on the metabolomic profile (p < 0.05). After FDR correction, 26 metabolites were significantly correlated with baseline handgrip strength. The strongest positive correlations were observed for creatinine (r = 0.53), leucine (r = 0.38), proline (r = 0.35) and isoleucine (r = 0.33). Baseline levels of leucine, isoleucine, PCaeC322 and SMOHC222 were associated with positive changes in handgrip strength (p < 0.05). CONCLUSIONS: Metabolomic changes were not related to protein type. However, metabolite levels were correlated with handgrip strength outcomes, suggesting the necessity to evaluate the metabolic state of individuals prior to interventions. TRIAL REGISTRATION: This study is registered on isrctn.com as ISRCTN16651067.