Reply to: Hypoxia treatment of Parkinson’s disease may disrupt the circadian system

Background Introduction In recent years, increasing attention has been given to hypoxia-based treatment for persons with neurodegenerative and mitochondrial disease, as reflected by the significant rise in publications from basic [1], preclinical [2] and clinical [3, 4] research groups. Hypoxia treatment is based on the idea of hypoxic conditioning and adaptations induced by hypoxia. Recently, we published a protocol paper to assess the safety, feasibility, and acute symptomatic effects of single sessions of continuous and intermittent hypoxia (for 45 min, at FiO2 0.133 and 0.163) in persons with Parkinson’s disease (PD) [3]. In Coste & Touitou’s recent correspondence [5] to our protocol [6], they highlighted the potential for circadian rhythm disturbances induced by hypoxia in PD. This interesting insight is based on their two different studies, in which a phase shift in circadian rhythm (as measured by cortisol and melatonin) was observed after eight-hours-long ‘chronic’ exposure to hypoxia [7, 8]. Coste & Touitou [6] carefully considered that hypoxia-based interventions could therefore induce changes in circadian rhythm, and this may in turn affect the outcome of these interventions. Here, we discuss important differences between chronic hypoxia, which resembles hypoxia as a disease model for sleep apnea, and hypoxic conditioning.