Synergistic effects of synbiotic, protein supplementation, and resistance training on inflammation, oxidative stress, and muscle strength in older adults with type 2 diabetes mellitus: a RCT triple-blinded study

BACKGROUND: Population aging poses major challenges for the management of type 2 diabetes mellitus (T2DM), particularly because inadequate protein intake, physical inactivity, and gut microbial dysbiosis may contribute to systemic oxidative stress and chronic low-grade inflammation (inflammaging). The present study investigated the combined effects of protein supplementation (P), synbiotic plus protein supplementation (SP), and resistance training (RT) on physical performance, body composition, glycemic control, inflammatory and oxidative stress parameters in older adults with T2DM. METHODS: This randomized, triple-blinded clinical trial included men aged ≥ 65 years with T2DM. Fifty-one participants were randomly allocated to one of three intervention groups: Control (n = 17), Protein (P; n = 17), or Synbiotic + Protein (SP; n = 17). Following withdrawals and losses to follow-up, 40 participants completed the intervention and were included in the final analyses (Control, n = 13; P, n = 13; SP, n = 14). RESULTS: All groups showed improvements in physical performance and an enhanced redox balance, as indicated by higher uric acid levels (an endogenous antioxidant) and lower plasma iron concentrations. Although all groups exhibited increased activities of the muscle damage markers lactate dehydrogenase and creatine kinase, the Protein group demonstrated greater improvements in muscle strength, reduced insulin resistance, and lower oxidative damage associated with heme-iron species. Furthermore, the pro-inflammatory cytokines IFN-γ and IL-6 were elevated in the Protein group, which may reflect their physiological role in exercise-induced metabolic adaptation and energy homeostasis rather than a detrimental inflammatory response. CONCLUSIONS: Protein supplementation combined with RT was associated with improvements in muscle strength, physical performance, insulin resistance, and selected biomarkers of oxidative stress. Under the conditions of the present study, the addition of synbiotic supplementation did not provide further benefits beyond those achieved with protein supplementation and resistance training alone.