Brain-Derived neurotrophic factor and inflammatory biomarkers are unaffected by acute and chronic intermittent hypoxic-hyperoxic exposure in geriatric patients: a randomized controlled trial

Animal and human studies have shown that exposure to hypoxia can increase brain-derived neurotrophic factor (BDNF) protein transcription and reduce systematic inflammatory cytokine response. Therefore, the aim of this study was to investigate the acute and chronic effects of intermittent hypoxic-hyperoxic exposure (IHHE) prior to aerobic exercise on BDNF, interleukin-6 (IL-6), and C-reactive protein (CRP) blood levels in geriatric patients. Twenty-five geriatric patients (83.1 ± 5.0 yrs, 71.1 ± 10.0 kg, 1.8 ± 0.9 m) participated in a placebo-controlled, single-blinded trial and were randomly assigned to either an intervention (IG) or control group (CG) performing an aerobic cycling training (17 sessions, 20 min·session⁻¹, 3 sessions·week⁻¹). Prior to aerobic cycling exercise, the IG was additionally exposed to IHHE for 30 min, whereas the CG received continuous normoxic air. Blood samples were taken immediately before (pre-exercise) and 10 min (post-exercise) after the first session as well as 48 h (post-training) after the last session to determine serum (BDNF_S) and plasma BDNF (BDNF_P), IL-6, and CRP levels. Intervention effects were analyzed using a 2 x 2 analysis of covariance with repeated measures. Results were interpreted based on effect sizes with a medium effect considered as meaningful (η_p²≥ 0.06, <i>d</i> ≥ 0.5). CRP was moderately higher (<i>d</i> = 0.51) in the CG compared to the IG at baseline. IHHE had no acute effect on BDNF_S (η_p²= 0.01), BDNF_P (η_p²&lt; 0.01), BDNF serum/plasma-ratio (η_p²&lt; 0.01), IL-6 (η_p²&lt; 0.01), or CRP (η_p²= 0.04). After the 6-week intervention, an interaction was found for BDNF serum/plasma-ratio (η_p²= 0.06) but not for BDNF_S (η_p²= 0.04), BDNF_P (η_p²&lt; 0.01), IL-6 (η_p²&lt; 0.01), or CRP (η_p²&lt; 0.01). BDNF serum/plasma-ratio increased from pre-exercise to post-training (<i>d</i> = 0.67) in the CG compared to the IG (<i>d</i> = 0.51). A main effect of time was found for BDNF_P (η_p²= 0.09) but not for BDNF_S (η_p²= 0.02). Within-group post-hoc analyses revealed a training-related reduction in BDNF_P in the IG and CG by 46.1% (<i>d</i> = 0.73) and 24.7% (<i>d</i> = 0.57), respectively. The addition of 30 min IHHE prior to 20 min aerobic cycling seems not to be effective to increase BDNF_S and BDNF_P or to reduce IL-6 and CRP levels in geriatric patients after a 6-week intervention. The study was retrospectively registered at drks.de (DRKS-ID: DRKS00025130).