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

Abstract

Background

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.

Patients and Methods

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, d ≥ 0.5).

Results

CRP was moderately higher (d = 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 < 0.01), BDNF serum/plasma-ratio (η_p² < 0.01), IL-6 (η_p² < 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 < 0.01), IL-6 (η_p² < 0.01), or CRP (η_p² < 0.01). BDNF serum/plasma-ratio increased from pre-exercise to post-training (d = 0.67) in the CG compared to the IG (d = 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% (d = 0.73) and 24.7% (d = 0.57), respectively.

Conclusion

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).

Keywords:

• Interleukin 6
• C-reactive protein
• BDNF
• hypoxia
• elderly

Acknowledgement

The authors thank AiMediqu S. A. Company Luxembourg for providing the ReOxy equipment and the software for implementing the intermittent hypoxic-hyperoxic exposure program. The authors also thank Alexey Platonenko for his great support in obtaining the ReOxy equipment and Margit Schmidt (Institute of Physiology, OVGU) for excellent technical assistance.

Author contributions

TB, OG, and LS contributed to conception and design of the study. TB, JI, and LS contributed to the implementation of the study. TB performed the data analysis. TBR and VL designed and performed the BDNF blood analysis. All authors contributed to the acquisition and interpretation of the data. TB and JI contributed to the manuscript drafting. RB, MB, OG, TBR, VL, and LS contributed to the review of the drafted manuscript. All authors have read and approved the submitted version of the manuscript.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Ethical approval

The experimental protocol was approved by the Otto-von-Guericke University Magdeburg (No. 202/20) confirming the principles of the Declaration of Helsinki on human experimentations. The study was retrospectively registered at drks.de (DRKS-ID: DRKS00025130).

Data availability Statement

The raw data supporting the conclusions of this article will be made available by the authors on reasonable request.

Additional information

Funding

German Center for Mental Health (Deutsches Zentrum für Psychische Gesundheit, DZPG) and State Saxony-Anhalt, funding number: 01EE2305D JE7 WP2 to Volkman Leßmann.