On the Use of a Hyperoxia Phase During Interval Hypoxia-Hyperoxia Training (IHHT): Diverging Opinions and Common Misunderstandings
There is disagreement and misunderstanding about the use of a hyperoxia phase during Interval Hypoxia-Hyperoxia Training (IHHT). In this article, I would like to address the effects of hyperoxia, review the current body of research, and share some practical recommendations that have proven effective in real-world applications.
A portion of the IHT community views the hyperoxia phase as essential for improving the effectiveness of hypoxia training, while another group rejects it entirely. I find myself between these opposing positions and am often misunderstood. My first blog post on this topic was published at a time when IHT had not yet become a promising therapeutic option for many post-COVID patients. Since then, new findings and more clinical experience regarding the use of the hyperoxia phase have emerged.
A hyperoxia phase can be an appropriate tool for reoxygenation following a hypoxia phase — but not for every patient. In particular, for patients in poor general condition, such as post-COVID patients, careful consideration should be given to how blood oxygen saturation is restored.
The Effects of the Hyperoxia Phase
A hyperoxia phase imposes oxidative stress on the body. As a result, excess oxygen can strengthen the body’s natural cellular defense mechanisms. The emphasis here is on “can.” As Paracelsus famously said: “The dose makes the poison.” The body’s antioxidant systems are already challenged during the hypoxia phase. An oxygen surplus increases this load even further and could overwhelm patients in poor condition.
When the intensity and duration of the hyperoxia phase are set appropriately, it stimulates the NRF2 signaling pathway (nuclear factor erythroid-2-related factor 2). This pathway regulates cellular defense mechanisms against oxidative damage. When oxidative stress or other harmful substances threaten the cells, NRF2 is activated, migrates to the cell nucleus, and triggers genes responsible for producing endogenous antioxidants such as glutathione, superoxide dismutase (SOD), and catalase.
If the stimulus is too strong, the oxygen concentration too high, or the hyperoxia phase too long, the NRF2 pathway is not activated. Instead, the NF-κB pathway (nuclear factor kappa-light-chain-enhancer of activated B cells) is triggered. This pathway plays a key role in immune and inflammatory processes, but does not stimulate antioxidant defense. On the contrary, NF-κB tends to promote inflammation.
Hyperoxia Phase – Yes or No?
There is ample scientific literature attributing pro-oxidative or pro-inflammatory effects to oxygen excess in both human and animal cells. One must bear in mind, however, that most studies have examined the long-term application of hyperoxia. This is an important point because some studies do indeed show benefits for IHHT, which may reinforce the opinion of its proponents. In clinical practice, however, results are less clear. In fact, in patients with severely reduced general condition, IHHT can often lead to deterioration.
When asked whether the hyperoxia phase is beneficial, I am often referred to newer studies showing positive effects in post-COVID patients. I do not dispute these results but want to point out certain study details: The participants were post-COVID patients with typical symptoms who had never been bedridden. All were able to travel to and from the clinic independently. Furthermore, the hyperoxia applied in these studies was relatively mild — with an average oxygen concentration of 30% in the inhaled air for only 2–3 minutes.
Defining Mild and Strong Hyperoxia
The oxygen concentration during the hyperoxia phase makes a decisive difference. Based on my literature review and discussions with IHHT researchers, the following seems reasonable: For healthy individuals and those with only minor health issues, a hyperoxia phase of 28–30% oxygen is recommended. This range is considered mild hyperoxia. Some believe that concentrations above 33% already constitute strong hyperoxia, and most scientists do not recommend levels above 40% for IHHT.
The Advantage of 25% Oxygen
An oxygen concentration of around 25% in the inhaled air is not perceived by the body as an excess. For most users, it is sufficient for adequate reoxygenation. For this reason, I consider 25% hyperoxia a good compromise — especially for patients whose oxygen saturation does not return to baseline during the normoxia phase.
One practical approach would be to use a hyperoxia phase with 25% oxygen concentration. Unfortunately, not all hypoxia devices allow for this setting. In such cases, for patients in poor condition, the hypoxia phase should be alternated with a normoxia phase.
If reoxygenation does not occur adequately during normoxia, removing the breathing mask can help. There are several possible explanations for this phenomenon. I have written a blog post about the impact of the breathing mask, but the air composition during normoxia may also contribute to the issue.
Note: Inaccuracies of 1–2% in oxygen concentration can occur depending on the hypoxia device and can affect blood oxygen saturation.
Practical Recommendations for Hyperoxia Settings
My rule of thumb: The higher the oxygen concentration, the shorter the hyperoxia phase should be.
An ideal starting point is a moderate enrichment of 25–28% oxygen for 2–3 minutes. The concentration can be increased over the course of IHT if appropriate.
To be on the safe side, I recommend measuring the Bioenergetic Health Index (BHI) before the first IHHT session. This is also advisable for owners of hypoxia devices that only offer hyperoxia with high oxygen concentrations. If the BHI is below 1.5, hypoxia-normoxia training should be performed instead due to the pre-existing oxidative burden.
My Conclusion on the Hyperoxia Phase
Interval Hypoxia Training with a normoxia phase stimulates the body’s antioxidant defense systems. When alternated with a hyperoxia phase, these defenses can also be enhanced — provided the body can tolerate the additional load. A hyperoxia phase is beneficial when it is properly dosed.
Discover my courses, workshops, and training programs on IHHT/IHT here: https://ecampus.hccacademy.de/s/hccacademy/en
Dr. med. Egor Egorov
