By Dr Mercola
Story at-a-glance
- Hypoxic training is successfully being used in the treatment of diseases such as asthma, high blood pressure, chronic inflammation and chronic infections, all of which are rooted in mitochondrial dysfunction
- The scientific application of intermittent hypoxic treatment started in Russia in the late 1970s. Early research showed it was radioprotective. When you reduce the partial pressure of oxygen in tissues that are being irradiated, there’s a significant protective effect on healthy tissues. Tumors are not protected, however, because they’re already hypoxic (hypoxic radioprotection)
- Intermittent hypoxia takes place during embryonic development. Scientists now hypothesize that this is a powerful mechanism that may control the quality of mitochondria
- One of the mechanisms that helps explain the benefits of hypoxia is that it raises your endogenous production of carbon dioxide (CO2) which, in turn, increases the efficiency of oxygen transport and metabolism
- One simple way to stimulate your mitochondrial function through intermittent hypoxia is to intermittently hold your breath. In clinical practice, oxygen-depleted air is intermittently administered using a hypoxic generator. The latest models include computerized biofeedback, and allow for all sorts of protocols to be administered
The interview above features Dr. Arkadi Prokopov, a Russian integrative medicine physician who specializes in hypoxic training and mitochondrial medicine. Optimizing your mitochondrial function is, of course, one of the most important strategies you can do to optimize your cellular energy, so it’s at the core of almost everything that you do to improve your health.
Prokopov graduated from Moscow Medical University in 1980. Most of his work has revolved around biomedical research, specifically research with professional divers. He did his postgraduate dissertation on the improvement of stress resistance in deep-sea divers.
After a decade of doing these kinds of studies, Russia started cutting research funding, so he returned to medical practice, where he began to apply his knowledge of diving physiology and controlled intermittent hypoxia (low oxygen) to the treatment of diseases such as asthma, high blood pressure, chronic inflammation and chronic infections.
“I was always interested, what is the best application of oxygen treatment to stimulate nonspecific, nonspecific [general] stress resistance?” he says. “And from many, many studies, it became clear, paradoxically, that the most efficient intervention is intermittent hypoxic treatment,” he said.
Intermittent Hypoxia Treatment
The scientific application of intermittent hypoxic treatment started in Russia in the late 1970s. Early research showed it was radioprotective.
• Hypoxia has selective properties — As explained by Prokopov, when you reduce the partial pressure of oxygen in tissues that are being radiated, there’s a significant protective effect on healthy tissues. Tumors are not protected, however, because they’re already hypoxic, so they’re not affected by the small, physiological decrease of oxygen partial pressure.
• Hypoxia begins at the embryonic stage — Early pioneers also discovered that intermittent hypoxia takes place during embryonic development. So, in utero, there are significant variations of partial pressure of oxygen.
It was not clear what the physiological purpose of these oscillations was, but now, decades later, “we understand that this is a powerful mechanism to control the quality of mitochondria,” Prokopov says.
• Other settings where intermittent hypoxia occurs — Intermittent hypoxia is also very common in other instances. “For instance, when we have some physical activity, when we stress our muscles, when they are contracted, the circulation is blocked and the muscle experiences [mild] hypoxia. Then, during relaxation, blood delivery [resumes] and muscles become again [saturated with] oxygen and nutrients,” Prokopov says.
He continues, stating that, “This is the universal mechanism which is providing continuous repair and recovery of the mitochondria and other cellular structures. So why not to use this natural mechanism for other purposes, like enhancement of endurance in athletes? Now, this is this very well known as altitude training. Thousands of athletes use altitude training.”
• How to create immediate hypoxia — As explained by Prokopov, one of the simplest ways to stimulate your mitochondrial function through hypoxia is simply to intermittently hold your breath.
Intermittent flow of oxygen-depleted air can also be administered via a face mask. These machines are known as hypoxic generators. The latest models also include computerized biofeedback, and allow for all sorts of protocols to be administered. I’ve been participating (involved?) in the development of such devices for the last two decades.
Basically, it cycles through the amount of oxygen you breathe, from the therapeutic low of 10% to 14%, to a high up to 21% to 34%.
Hypoxia and the Role of Carbon Dioxide
One of the mechanisms that helps explain the benefits of intermittent hypoxia training is that it raises your carbon dioxide (CO2) which, in turn, increases the efficiency of oxygen transport and metabolism. The hypoxia also relaxes your capillaries. In your brain, hypoxia increases blood perfusion up to 40%. This is a normal physiologic hypoxic response, and CO2 plays a significant role.
• Control your breathing — If you routinely overbreathe (breathe too deeply or too rapidly, or both), you end up with lower CO2 levels than are ideal. This kind of subclinical hyperventilation is frequently a learned response to stress, and needs to be unlearned — something we discuss in my interview with Peter Litchfield, which will be posted next week.
• Healthier mitochondria help you stop overbreathing — Interestingly, Prokopov claims that once people improve the quality of their mitochondria, they typically stop overbreathing automatically. He explains, “Because where do we get carbon dioxide from? From the mitochondria. It’s an element metabolite, the byproduct of oxidative phosphorylation. And if the mitochondria are not active enough, they just don’t produce enough carbon dioxide.”
• Most people don’t generate enough carbon dioxide — Normally, the urge to breathe is stimulated and regulated by a slight increase in CO2, which happens in any physical activity.
But today, in stressful situations, we rarely switch on the “fight-or-flight” response that raves up metabolism and raises CO2 production. Instead, we have only a fast increase of CO2 removal by accelerated breathing, but without an increase of physical activity that would produce more CO2 and would compensate for its drop.
Add stress, when you hyperventilate even more, which further reduces your CO2 level. Before you know it, you’re in a vicious doom loop that can send you to the emergency room.
• An easy way to induce hypoxia — One way to increase the amount of CO2, thereby breaking this loop, is to breathe into a paper bag. That can reduce many symptoms of overbreathing and hyperventilating in just a couple of minutes. A hypoxia generator can also be used. The drawback of these kinds of tools is that they only offer temporary relief.
“It’s just a symptomatic treatment if used only sporadically,” Prokopov says. “As soon as you stop it, you overbreathe again and you have the same problems. But if regenerate your mitochondria, if you make them work more efficiently, more economically, it produces a much better level of endogenous carbon dioxide.
Normal partial pressure of carbon dioxide in blood plasma is from 35 to 45 torr, but most people are below 35. If mitochondria are functioning optimally, it automatically [resets the partial pressure of CO2] and we see reduction or complete elimination of all problems connected to overbreathing.”
The Most Efficient Way to Optimize Mitochondrial Function
One simple and most useful strategy to optimize your mitochondrial function is to eat the right carbs, in optimal amounts; simultaneously limiting fats. The reason for this is because glucose metabolism, when it occurs in the mitochondria, optimizes CO2.
• Glucose metabolism is preferred to fat metabolism — As mentioned, virtually all the CO2 is produced in the electron transport chain of your mitochondria. Fat metabolism reduces mitochondrial efficiency by 25% to 50%.
• More structured water is produced — Glucose metabolism also increases structured water (mitochondria-produced water), also known as deuterium-depleted water, and reduces reactive oxygen species (ROS) production in the mitochondria.
Naturally, oxidative damage is a major contributor to ill health and premature death, so you want to minimize ROS production as much as possible. Prokopov comments:
“First of all, I must say that if you don’t load your mitochondria continuously, they automatically degrade. What do I mean by load? The mitochondria can feel only two interventions, two inputs — the amount of fuel, and the amount of oxygen.
If there is a continuous flow of fuel — nutrients — and a continuous, stable level of oxygen, the mitochondria undergo degradation, because during this ad libitum nutrition and ad libitum oxygen, oxidative damage in mitochondrial DNA results in a growing population of damaged mutated mitochondria, and mutated mitochondria have smaller DNA molecules.
Normal metabolism results in continuous mutation and it makes the mitochondrial DNA smaller, because mutations are repaired very insufficiently. In a stable situation, what molecules will reproduce faster?
The smaller molecule will make copies a little bit faster than the larger, therefore, if everything is stable, normal, the mutated disadvantaged mitochondrial DNA will dominate, and we see it with the normal aging process (as clonal expansion of mutated mtDNA).
We see it in some diseases also, especially in neurodegenerative diseases. And of course with chronic infection. So the task is to continuously eliminate, or help the natural process of elimination of mutated mitochondria. If we just help this natural process of mitochondrial regeneration, we prevent accelerated decline of mitochondrial quality.
And the best tool for this is intermittent hypoxic training, because … the aged mitochondria are much more sensitive to O2 oscillations. They don’t have enough protective mechanisms because mitochondrial DNA protects itself, but mutated mitochondria don’t have enough of these [protective] enzymes, so they are just killed by the oscillations [intermittent highs and lows of O2].”
Why Intermittent Fasting Doesn’t Always Work
So, to summarize, your mitochondria need fuel and oxygen, but both of these inputs are needed in a cyclical or intermittent fashion.
Continuous fuel is a disaster and so is continuous oxygen. Both need to be augmented and throttled back at intervals. This would suggest that intermittent fasting is an ideal strategy. Or is it? Prokopov comments:
“What I see, and a lot of research and experience in the clinical field [shows], is that in the fasting state, when your ketone metabolism is much higher, the mitochondrial energy production is more optimal when we have healthy mitochondrial population.
But when the mitochondrial population is a mix of mutated and healthy mitochondria, [fasting] can cause problems. Many people cannot start fasting, they cannot start intermittent fasting or go on a ketogenic diet, because they have, let’s say, 50% mitochondria that are dysfunctional.
As soon as we repair the mitochondria with gradually introduced intermittent fasting, gradually introduced ketones, and in parallel, intermittent hypoxic training, we see immense improvement of energy metabolism, we see improvement of OXPHOS and ATP production, and most interestingly, much more economical [energy production].
So, mitochondria in an idling state consume much less oxygen. On the other hand, they’re much more efficient. So, we’re improving quality of the mitochondria … Most patients [with mitochondrial dysfunctions] show very low mitochondrial energy production.”
• Switch your schedule once mitochondrial health improves — Once your mitochondria are sufficiently healthy to handle intermittent fasting, Prokopov suggests an 8/16 schedule, where you eat all your meals within an eight-hour window, and fast for the remaining 16 hours.
• Shorten the eating window further — As your metabolic flexibility improves, which is also wholly dependent on the functionality of your mitochondria, your eating window can be narrowed to six hours or even less. Prokopov personally eats all his meals within a four- to five-hour window. Intermittent fasting also works synergistically with hypoxic training.
[…]
Via https://articles.mercola.com/sites/articles/archive/2025/03/16/intermittent-hypoxia.aspx
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