In my recent articles, I’ve been exploring Nrf2, one of the fascinating systems our cells use to respond to oxidative stress and activate their own protective mechanisms.
We’ve looked at food. We’ve looked at functional mushrooms. But there’s another way researchers are investigating our ability to adapt at a cellular level — and this one involves changing the amount of oxygen we breathe.
It’s called IHHT: Intermittent Hypoxia-Hyperoxia Training.
I’ve recently been experiencing IHHT myself at BIOGENA in London, and it brought me back to a concept I’ve mentioned several times recently:
Hormesis.
The idea that sometimes a small, carefully controlled challenge can encourage the body to adapt.
What exactly is IHHT?
IHHT stands for Intermittent Hypoxia-Hyperoxia Training. During a session, you rest while wearing a breathing mask. The concentration of oxygen you breathe is altered in controlled intervals. During the hypoxic phase, oxygen availability is reduced, creating conditions similar to those experienced at altitude. This alternates with a hyperoxic phase, when the oxygen concentration is increased.
BIOGENA describes its IHHT approach as alternating precisely controlled periods of reduced and increased oxygen, with the aim of creating an adaptive stimulus. It might sound rather dramatic. In practice, you’re lying down breathing through a mask.
The interesting part is what’s happening inside the body.
Why would we deliberately reduce oxygen?
We normally think of oxygen very simply:
More = good. Less = bad.
Biology, unsurprisingly, is more complicated. Our cells are constantly sensing their environment and adjusting to changes in nutrients, energy demand, temperature, oxygen and other factors.
When oxygen availability temporarily falls, cells don’t simply sit there waiting for more oxygen.
They respond.
They alter cellular signalling and metabolism to adapt to the changing conditions. This ability to sense and adapt to oxygen availability is fundamental biology. And it’s one reason altitude training has long been used by athletes. IHHT takes the principle of intermittent exposure to lower oxygen and applies it under controlled conditions.
Meet hormesis again
This brings us back to hormesis.
Hormesis describes the idea that a relatively small stressor can stimulate an adaptive response that may make the organism better prepared to cope with subsequent challenges. Exercise is perhaps the easiest example. During exercise, we deliberately put the body under stress. Our heart works harder. Energy demand rises. Reactive oxygen species temporarily increase. Muscles experience microscopic damage. If we looked only at what was happening during exercise, we might wonder why anyone thought it was a good idea.
But then comes:
Adaptation.
And recovery.
The body responds to the challenge. Heat, cold, fasting and altitude exposure are other areas in which researchers investigate hormetic responses. Intermittent hypoxia belongs to this same broad family of controlled physiological challenges.
What do mitochondria have to do with it?
Quite a lot. Mitochondria are often described as the powerhouses of our cells because they’re central to producing the energy our cells need. And oxygen is intimately involved in that energy production. When oxygen availability changes, mitochondria are therefore right in the middle of the cellular response. This is one of the principal areas highlighted in IHHT research and in BIOGENA’s explanation of the technique. BIOGENA describes IHHT in terms of mitochondrial function, cellular metabolism and energy production.
Again, though, it’s worth separating an interesting biological mechanism from a promise that IHHT will “fix” your mitochondria. We’re talking about stimulating adaptation, not replacing or repairing individual mitochondria on command.
And where does Nrf2 come in?
This is where IHHT connects with the subject we’ve been exploring over the past few weeks. Nrf2 is one of the systems involved in how cells respond to oxidative and metabolic stress. Normally, Nrf2 activity is tightly regulated. When cells encounter particular stress signals, Nrf2 can accumulate and move into the nucleus, where it influences genes involved in antioxidant defence and cellular protection.
So Nrf2 isn’t simply about consuming antioxidants. It’s part of our adaptive response to stress. And that gives us a useful way of thinking about intermittent hypoxia. A temporary challenge changes the cellular environment. The cell senses that change. Protective and adaptive signalling systems respond. And once the challenge has passed, the body has an opportunity to recover.
That’s hormesis in action.
But does IHHT “activate Nrf2”?
This is where I’d add a little caution. It’s tempting to take our understanding of hypoxia, oxidative signalling and Nrf2 and turn it into a neat statement:
“IHHT activates Nrf2.”
The biology isn’t quite that simple. Nrf2 interacts with numerous other cellular pathways, and responses can vary according to the intensity and duration of the stressor, tissue involved, health status and other individual factors.
BIOGENA itself promotes IHHT in relation to mitochondrial and cellular metabolism, respiratory function, performance and adaptation to altered oxygen availability. Its public information doesn’t present IHHT primarily as an Nrf2 treatment.
So I think it’s more accurate — and more interesting — to view Nrf2 as one part of a much larger adaptive network that helps cells respond to changing conditions.
Stress isn’t always the enemy
Perhaps that’s the bigger lesson in all of this. We’re accustomed to hearing that we should reduce stress. And when we’re talking about persistent psychological or physiological stress without adequate recovery, that’s understandable.
But our bodies aren’t designed to experience no challenge whatsoever. Movement challenges us. Temperature changes challenge us. Going without food for a period challenges us. Altitude challenges us. And these short-term stressors can provide information that tells our biology:
Something has changed. Adapt.
That is very different from remaining under relentless stress with no opportunity to recover.
The pattern matters:
Challenge → response → adaptation → recovery
Can more hormesis always be better?
No.
And this is particularly important when we move from ordinary lifestyle behaviours such as exercise into deliberate interventions. A stressor is beneficial only within an appropriate context. What represents a manageable challenge for one person may be inappropriate for another. That’s why technologies involving altered oxygen shouldn’t simply be treated as another wellness trend to try because “stress is good for you”.
Individual health, the degree of hypoxia, duration, frequency and recovery all matter. Even BIOGENA’s broader discussion of biohacking acknowledges that there isn’t a single approach that suits everybody.
From antioxidants to adaptation
One thing I find particularly interesting about the Nrf2 research we’ve been exploring is how it changes the way we think about cellular protection.
For years, much of the popular conversation around oxidative stress was:
Free radicals are bad. Antioxidants are good. Therefore, consume more antioxidants.
We now understand that reactive oxygen species also act as signalling molecules. Some oxidative stress is part of normal biology. Exercise itself temporarily increases it. The goal therefore isn’t necessarily to eliminate every oxidative challenge. It’s to maintain the ability to respond appropriately to that challenge. That’s a very different model of health.
Food, mushrooms, movement — and oxygen
Over the past few weeks we’ve arrived at Nrf2 from several apparently unrelated directions.
Plant compounds.
Functional mushrooms.
Exercise.
And now intermittent changes in oxygen availability. They’re not interchangeable interventions and they certainly don’t all do exactly the same thing. But they illustrate a common biological theme:
Our bodies are dynamic systems designed to sense their environment and adapt to it.
Perhaps cellular resilience isn’t created by protecting ourselves from every challenge. Perhaps part of resilience lies in retaining the ability to meet an appropriate challenge, respond to it, recover and adapt.
IHHT gives us another fascinating window into that process.
And after experiencing it myself, it’s certainly an area of research I’ll be watching with interest.
Further reading
BIOGENA — Metabolic Air / IHHT
Information about BIOGENA’s approach to intermittent hypoxia-hyperoxia training.
BIOGENA — What is Biohacking?
An introduction to hormetic approaches including exercise, temperature exposure and IHHT.
Previous article:
Meet Nrf2: The Cellular Defence System You’ve Probably Never Heard Of
Related article:
Functional Mushrooms and Nrf2: What Does the Research Actually Show?
