Grégoire Millet recently published (worth a read @John_Hemming): Mechanisms underlying the health benefits of intermittent hypoxia conditioning 2023
Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies.
In elderly adults (≥65 years), moderate sleep apnoea (apnoeic index 20–40/h) was associated with a significant survival advantage, in comparison with age-, sex and ethnicity-matched national mortality data (Lavie & Lavie, 2009), exemplifying the importance of the hypoxic dose.
These protocols typically consist of repeated 4–8 min exposures to hypoxia, i.e. fractions of inspired oxygen (FIO 2 = 10–15%, alternating with 2–5 min exposures to normoxia (IHE: FIO 2 = 21%) or hyperoxia (IHHE: FIO 2 = 30–35%), totalling 35–40 min/session applied 3–5 times per week for 3–8 weeks. IHHE has also been termed intermittent hypoxia hyperoxic conditioning (IHHC)
Much remains to be optimized to fully harness the potential of hypoxia conditioning. It is essential that the different basic and clinical research fields harmonize their understanding and communication of hypoxia conditioning research, differences in adaptation to continuous hypoxia vs. IH be better described, and individually optimal hypoxic doses systematically established. It will be especially important to establish organ/function-specific hypoxic dose thresholds that allow the eliciting of specific benefits, without triggering maladaptation in other organs. For example, a severe IH protocol (90 s cycles of 10% and 21% oxygen for 8 h/day for several weeks; Wu et al., 2015) reduced pain responses in rats, but similar IH protocols elicit maladaptive sympathoexcitation and cardiovascular remodelling in rodents.
In addition, several practical questions related to hypoxia conditioning remain, including: how long do respective benefits persist after concluding hypoxia conditioning? Once the improvements wane, can abbreviated hypoxia conditioning programmes restore them? Do medications or dietary supplements, e.g. β-adrenoceptor antagonists or antioxidants, interfere with hypoxia conditioning outcomes, as shown for cardio(Mallet et al., 2006) and cerebroprotection (Jung et al., 2008) in animals? Lastly, which conditioning protocols are most effective for different applications in prevention, rehabilitation and performance enhancement (including comparisons of IHE and IHHE)?
He also wrote last year: Hypoxia Sensing and Responses in Parkinson’s Disease 2024
We describe cases suggesting that hypoxia may trigger Parkinsonian symptoms but also emphasize that the endogenous systems that protect from hypoxia can be harnessed to protect from PD.
These effects of inspiratory hypoxia likely overlap with and may, to some degree, reproduce or amplify so-called “functional hypoxia” caused by increased oxygen demand, for example, in skeletal muscle during exercise or in the brain due to motor-cognitive training [102,103,104]. Therefore, “functional hypoxia” may also play a role in the well-documented benefits of exercise [35] and motor–cognitive training in PD.
However, even though clinical trials are on the way and will provide important new information on individual responses to hypoxia in people with PD, we probably should not expect to be able to appreciate the full potential of hypoxia conditioning in PD too soon. The determination of the hypoxic doses required to induce an optimal effect while also minimizing hypoxia-associated risks will be a major future challenge, especially since many parameters have to be optimized, including the intensity, duration, and frequency of the hypoxic stimulus, but also the type of hypoxia (normobaric versus hypobaric), the role of CO2 levels (isocapnic versus poikilocapnic hyperventilation in hypoxia reduces CO2 levels), and various environmental (e.g., temperature) and behavioral (e.g., activity level) factors likely play a decisive role. Increased CO2 levels, by themselves or in combination with hypoxia (e.g., by adding CO2 to the breathing gas), for example, promote ventilatory plasticity and increased cerebral blood flow. While the evidence is mounting that responses to oxygen level changes are crucial in neurological diseases, and especially PD, understanding the role of the factor oxygen requires systematic investigation.
