Safety and first promising results of a long-term human hypoxia protocol with uniquely comprehensive monitoring

by Maren Franta née Hansen-Hagge
Doctoral thesis
Date of Examination:2025-01-29
Date of issue:2024-12-19
Advisor:Prof. Dr. Dr. Hannelore Ehrenreich
Referee:Prof. Dr. Dr. Hannelore Ehrenreich
Referee:PD Dr. Julie Schanz
Persistent Address: http://dx.doi.org/10.53846/goediss-10963

 

 

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Abstract

English

Human cells can adapt to reduced oxygen (O2) conditions and impaired metabolism. Therefore, hypoxia evolves to be a critical physiological driver for improved performance. A demand-driven reduced oxygen availability occurring under motor-cognitive training is termed “functional hypoxia”. Similar to inspiratory hypoxia, functional hypoxia induces transcriptional changes within the cell metabolism. Given the promising changes caused by exposure to hypoxia in rodents, a translational human project was started. It combines moderate inspiratory and functional hypoxia. The objective of the here presented exploratory study is to prove the safety of hypoxic exposure and to generate a standardized protocol for a blinded study that aims to develop a non-pharmacological treatment for cognitive decline in psychiatric patients. A total of 20 subjects were enrolled: 13 healthy individuals and seven patients with depression and/or autism spectrum disorders. Motor-cognitive training under inspiratory hypoxia (12% O2) for 3.5 hours over three weeks with six training days each proved well tolerated. Several vital parameters were observed in a regular weekly (blood parameters, immune cells), daily (side effects, blood pressure), or even second-wise (saturation, heart rate) manner. All parameters revealed no harmful effects. Adaptation of the organism could be demonstrated. The chosen dose appeared appropriate to gain the desired effect without negative influence. Cognitive and physical performance were assessed in a standardized manner before and after hypoxia exposure. Significant improvements were observed for V̇O2max (maximal workload in standardized ergometer step load test [ml/min]) p=0.003, p=0.08 for patient’s subgroup; TTE (time to exhaustion [s]) p=0.0009, p=0.05 for patient’s subgroup; sum heart rate [bpm] in ergometer step load test pre- and post-exposure to hypoxia for a similar amount of work p=0.02; and cognitive composite score p=0.014 with a Cronbach’s alpha of 0.75. Depressive symptom burden was reduced according to psychopathology questionnaires (Brief Symptom Inventory (BSI), Beck Depression Inventory (BDI), and Hamilton Depression Rating Scale (HAMD-17)). The data presented here provide evidence for the protocol’s safety and the first signals of a positive effect on cognition, psychopathology, and physical fitness. The structured and standardized training protocol of a planned single-blind, randomized, placebo-controlled trial will be based on the data from the exploratory pilot study presented in this work.
Keywords: brain; erythropoietin; functional hypoxia; oxygen saturation; physical performance; adaptation to hypoxia