Background: Brain-derived neurotrophic factor (BDNF) supports neural plasticity and cognitive function, while tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine linked to systemic inflammation. Exercise and breathing techniques may modulate these markers, but their combined effects in healthy non-athletic individuals remain underexplored. This study investigated the effects of 12 weeks of diaphragmatic breathing exercises (DBE), alone and combined with aerobic training (AT), on plasma BDNF and TNF-α concentrations in healthy young men.

Methods: Forty-five non-athletic aged 18–25 years were randomly assigned to three groups: control (CONT, n=15), DBE (n=15), and DBE + AT (n=15). The DBE protocol involved twice-daily pursed-lip and abdominal breathing sessions. Aerobic training consisted of progressive running at 70–75% HRmax. Plasma BDNF and TNF-α were measured before and after the 12-week intervention using enzyme-linked immunosorbent assay (ELISA). Post-intervention blood samples were obtained 48 h after the final training session under standardized fasting conditions.

Results: Repeated-measures analyses demonstrated significant differences in BDNF and TNF-α across the study groups (P<0.001). For BDNF, the reported between-group effect was F=57.47, P<0.001. Bonferroni-adjusted comparisons demonstrated significant differences between CONT and DBE, CONT and DBE + AT, and DBE and DBE + AT. For TNF-α, a significant overall group effect was observed (F=14.51, P<0.001), with significant differences between CONT and DBE and CONT and DBE + AT.

Conclusion: Twelve weeks of DBE, alone and combined with aerobic training, were associated with significant between-group differences in plasma BDNF and TNF-α in healthy non-athletic young men.