Aim Chronic inflammation is one of the major challenges in the management of obesity and type 2 diabetes mellitus (T2DM). Our primary aim was to assess the anti-inflammatory effects of Saffron (Crocus sativus L.) supplementation and concurrent training in obese men with T2DM. Methods Sixty obese men with T2DM (age = 39 ± 5 years; body mass = 93.9 ± 6 kg) were randomly assigned to four groups; concurrent training + placebo (CT; n = 15), saffron supplementation (S; n = 15), concurrent training + saffron supplementation (CTS; n = 15), or control (CON; n = 15). The participants in the CT group performed concurrent training (resistance + aerobic) three times per week for 12 weeks and received daily one pill of placebo (maltodextrin); the participants in the S group supplemented with one pill of 100 mg of saffron daily, and the participants in the CTS group participated in both saffron and training intervention while CON group continued regular lifestyle (no training or no supplementation). Inflammatory markers, body composition (evaluated by a multi-frequency bioelectrical impedance device; Jawon X-Contact 356), and metabolic profile were evaluated before and after interventions. Results All three interventions significantly (p<0.05) decreased TNF-α (CT = -4.22, S = -1.91, CTS = -9.69 pg/mL), hs-CRP (CT = -0.13, S = -0.1, CTS = -0.32 ng/mL), IL-6 (CT = -6.84, S = -6.36, CTS = -13.55 pg/mL), IL-1β (CT = -8.85, S = -6.46, CTS = -19.8 pg/mL), FBG (CT = -6.97, S = -2.45, CTS = -13.86 mg/dL), insulin (CT = -0.13, S = -0.03, CTS = -0.21 mU/L), HOMA-IR (CT = -0.12, S = -0.04, CTS = -0.21), HbA1c (CT = -0.17, S = -0.11, CTS = -0.26 %), and increased IL-10 (CT = 1.09, S= 0.53, CTS = 2.27 pg/mL) concentrations. There was a positive correlation between changes in BFP with hs-CRP, IL-6, IL-1β, and TNF-α, and IL-10 concentrations across the intervention groups. Additionally, significant differences were observed between the changes for all variables in the CTS group compared to CT, S, and CON groups. Conclusion It seems that an interactive of saffron supplementation and concurrent training has more efficient effects on the anti-inflammatory status compared to the saffron supplementation or concurrent training alone.

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