Is a hyperventilation+hypoventilation breathing exercise (Wim Hof Method) more likely to prevent or promote cancer?

Question

Apart from exposure to cold, the core element of the Wim Hof Method is a breathing technique, which alternates between hyperventilation and hypoventilation (apparently similar to Tummo meditation). It consists of repeating the following steps for 3-4 times:

• Hyperventilation for 30 deep, strong breaths.
• Breath hold after an exhalation for as long as possible.
• Inhalation followed by another breath hold for ~10 seconds.

The exercise seems to have a profound effect on human physiology, which has been discovered in Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. The focus of the experiment was to study the immune response after administration of an endotoxin while performing the breathing exercise. The study revealed the following physiological reactions (see also videos in the supplementary material):

• Increases epinephrine levels.
• Suppresses immune response, i.e., decreased pro-inflammatory mediators (TNF-α, IL-6, IL-8) and increased anti-inflammatory mediators (IL-10).
• Blood pH: Increases from ~7.4 to over ~7.7 during hyperventilation (respiratory alkalosis); falls back to ~ baseline during breath retention.
• Oxygen saturation: At 100% during hyperventilation; temporarily drops to ~50% during the breath hold.
• Arterial pCO2: Decreases from a baseline of ~4.5 kPa to below 2 kPa during hyperventilation. The breath hold recovers pCO2 but not fully to baseline level, which is why the minimum pCO2 seems to decrease with each hyperventilation.
• Arterial pO2: Increases from a baseline of ~16.5 to kPa over 22 kPa during hyperventilation. During the breath hold pO2 can fall below 4 kPa, and the minimum seems to become lower with each repetition. pO2 stays slightly elevated post exercise.

Looking at these physiologic reactions, I'm wondering how performing this exercise on a daily basis would affect the development of cancer? I am a scientist, but not in the field of medicine or health, so it is difficult to make sense these effects. Naively, I would think that some of the reactions like the more alkaline blood pH and a more efficient immune system should be beneficial for preventing cancer. Also, a 2017 study has found positive effects of breath training on respiratory cancer. On the other hand, the exercise involves states of low oxygenation during both:

• Hyperventilation: As a result of the low carbon dioxide levels, haemoglobin binds oxygen (Bohr effect), leading to reduced tissue oxygenation.
• Breath hold: The low oxygen saturation and arterial pO2 probably means that the body is in a temporary state of generalized hypoxia at the end of the breath hold.

A quick research on the connection between oxygenation/hypoxia and cancer seems to indicate that hypoxia is something that should be avoided by all means, because it promotes malignant progression and metastasis, and increases resistance to therapy and mortality (Wikipedia, 2004 article, 2007 article, 2016 article).

Is it possible for an experienced health scientist to put these observations into perspective? I.e., would you recommend (or advise against) a cancer-prone person to do such an exercise from a purely theoretical point of view?

Answer 1

Apart from monks and nuns who showcase impressive abilities Wim Hof is onto something. One anecdote reads as follows:

I’ve also experienced the positive changes myself, […] My cardiovascular and muscular endurance has increased substantially too, with a reduction in my run times, thanks to the over-saturation of oxygen to my cells, activation of my autonomic nervous system and the overriding my hypothalamus, and the changing of my body’s pH level to a more alkaline state. All the changes to my physiology from practicing the Wim Hof Technique consistently, has improved my overall health and athletic performance considerably.

But anecdotes from believers are of course not very useful. Scientists are nevertheless intrigued by all those world records Hof has collected:

At first this seems a ridiculous idea, because our body’s innate immune system has long been known to operate in an autonomic fashion: we can’t voluntarily control it. But what if this understanding was wrong? Dutchman Wim Hof, better known as “the iceman”, certainly thinks so. Hof holds several world records for withstanding extreme cold, such as immersion in ice for almost 2 hours. Over the years, he developed techniques that allowed him to withstand low temperatures. These include meditation, breathing methods and repeated exposure to cold. But he also made the outlandish claim that he could exert control over his immune system. In 2011, although we were sceptical, we put Hof’s claim to the test. […] When we got back to the Netherlands, we tested the volunteers’ immune responses using the endotoxin model. The results were remarkable: the volunteers trained by Hof, who practised the breathing techniques during the experiment, showed exceptionally high adrenaline levels – even higher than those measured in people bungee jumping for the first time (PNAS, vol 111, p 7379). They also reported fewer flu-like symptoms, experienced lower fevers and had cytokine levels of less than half those of the control group. These results show, for the first time, that it is indeed possible to voluntarily influence the SNS and hence the innate immune system.

The same study in a peer reviewed journal comes with more data:

Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans:

Significance Hitherto, both the autonomic nervous system and innate immune system were regarded as systems that cannot be voluntarily influenced. The present study demonstrates that, through practicing techniques learned in a short-term training program, the sympathetic nervous system and immune system can indeed be voluntarily influenced. Healthy volunteers practicing the learned techniques exhibited profound increases in the release of epinephrine, which in turn led to increased production of anti-inflammatory mediators and subsequent dampening of the proinflammatory cytokine response elicited by intravenous administration of bacterial endotoxin. This study could have important implications for the treatment of a variety of conditions associated with excessive or persistent inflammation, especially autoimmune diseases in which therapies that antagonize proinflammatory cytokines have shown great benefit.

Abstract Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases.

A second study also sees changes resulting from practicing the technique, this time stripping the method of its Asian mysticism parts and thereby westernising it: Neurocognitive and somatic components of temperature increases during g-tummo meditation: legend and reality:

Stories of g-tummo meditators mysteriously able to dry wet sheets wrapped around their naked bodies during a frigid Himalayan ceremony have intrigued scholars and laypersons alike for a century. Study 1 was conducted in remote monasteries of eastern Tibet with expert meditators performing g-tummo practices while their axillary temperature and electroencephalographic (EEG) activity were measured. Study 2 was conducted with Western participants (a non-meditator control group) instructed to use the somatic component of the g-tummo practice (vase breathing) without utilization of meditative visualization. Reliable increases in axillary temperature from normal to slight or moderate fever zone (up to 38.3°C) were observed among meditators only during the Forceful Breath type of g-tummo meditation accompanied by increases in alpha, beta, and gamma power. The magnitude of the temperature increases significantly correlated with the increases in alpha power during Forceful Breath meditation. The findings indicate that there are two factors affecting temperature increase. The first is the somatic component which causes thermogenesis, while the second is the neurocognitive component (meditative visualization) that aids in sustaining temperature increases for longer periods. Without meditative visualization, both meditators and non-meditators were capable of using the Forceful Breath vase breathing only for a limited time, resulting in limited temperature increases in the range of normal body temperature. Overall, the results suggest that specific aspects of the g-tummo technique might help non-meditators learn how to regulate their body temperature, which has implications for improving health and regulating cognitive performance.

That sounds indeed promising. But in what way remains mostly unclear. "Attenuating immune response"? Well, lowering the immune system's activity might be a bad idea in relation to cancer, putting a brake on overshooting inflammatory processes might be good. Is any of this studied in a larger group? Is any of this studied over a longer time frame?

Temporary short time hyperventilation or even hypoxia may have some kind of training effect that might lead to improved oxygenation of body tissues overall. Doing this repeatedly or routinely may also have quite unwelcome effects. But the local 'tumor hypoxia' effects of cancer that appear as sustained under-oxygenation of the affected cells are not necessarily the same as what happens in breathing a few times like the Hof.

There is, however, a string attached to the Wim Hof Method, that is the risk that people may think the method is scientifically valid. Wim is a wholehearted speaker, but his scientific vocabulary is galimatias. With conviction, he mixes in a non-sensical way scientific terms as irrefutable evidence. Many less scientifically literate people believe what he says and several seriously diseased people have used his method as the final straw. Stories of believers circulate on the Internet, in popular magazines and are broadcasted as well. The scientific investigations are often presented with a biased view.
When practicing the Wim Hof Method with a good dose of common sense (for instance, not hyperventilating before submerging in water) and without excessive expectations: it doesn't hurt to try. Although the effects on our health wait to be proven, people may feel healthier.
All in all, I think it is worthwhile to sort out whether and which of the training aspects of Wim's method affect our immune system and metabolism. And, with respect to the extreme challenges, is Wim special? Or are we all, as he himself proclaims, ice(wo)men?[emphasis added]

Summary

So, Wim Hof is onto something. But what is it? Western science has optimised meditation techniques and proven many benefits one can gain from these practices, even in their archaic or mysticised form. Better breathing patterns and more activity as opposed to sedentary life are without question positive changes for many 'civilised' people.

This answer assumes a somewhat mediated approach to the technique. There are always extreme cases that seem to invalidate a common sense evaluation. Trying to do this in a "cancer prone" individual? The relation to cancer seems currently indirect at best. If you overdo it, and what is meant by that is completely undetermined, it is very probably bad. As Taylor above has found this post:
13 observations after 5 months and 200+ sessions of Wim Hof Breathing Method some aspects become quite clear though: 120 minutes sessions, doing in a car or in icy water, and possibly alone, there are quite a number of such immediate risks involved in practicing this to these extremes. How much more likely cancer is due to these exercises if done so often and so long to really stress out and damage the system is not known via scientific studies. Overdoing it will very probably lead to very unwelcome effects, like driving off the road, so quickly that any increase in risk for cancer will be moot.

Unless this Hof-method or the tummo meditation are more researched we have to conclude for now that there are many anecdotes but almost no real evidence as defined to our standards that this works either way or better than simply "do more sports". Only indicators, but a few, point into the direction of overall improved health, if one doesn't faint from the hyperventilation.

Being the optimist I await much more studies on this. Until those arrive: I guess it doesn't hurt much, it doesn't help much.

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Answer 2

Hyperventilation can lead to reduced oxygen transport to cells. As a result, ineffective breathing patterns can cause cell and tissue hypoxia, chronic inflammation, immunosuppression, and many other negative effects caused by low body-oxygen levels and hypocapnia (reduced CO2 levels).

Hypoxia has been found to be a driving force in several health conditions including heart disease, diabetes, chronic fatigue, and has become a widely known key cause of cancer on the cellular level.

Dr. Otto Warburg investigated the metabolism of tumors and the respiration of cancer cells. In 1931, he was awarded the Nobel Prize for his discovery of the nature and mode of action of the respiratory enzyme as it relates to cellular metabolism and cellular respiration. His studies led to the discovery that

...cancerous cells can live and develop, even in the absence of oxygen.

Under normal conditions, abnormal cells are detected by the immune system and destroyed. However, the work of macrophages, enzymes and other agents of the immune system is severely restricted when hypoxia exists.

For example, Dr. Rockwell from Yale University School of Medicine studied malignant changes on the cellular level and wrote in an abstract, titled ‘Oxygen delivery: Implications for the biology and therapy of solid tumors,’

The physiologic effects of hypoxia and the associated microenvironmental inadequacies increase mutation rates, select for cells deficient in normal pathways of programmed cell death, and contribute to the development of an increasingly invasive, metastatic phenotype.

Malignant cells normally and constantly appear and exist in any human organism due to the billions of cell divisions and mutations. As described in ‘Molecular Biology of the Cell. 4th Edition,’

A tumor is considered cancer only if it is malignant, that is, only if its cells have acquired the ability to invade surrounding tissue. Invasiveness usually implies an ability to break loose, enter the bloodstream or lymphatic vessels, and form secondary tumors, called metastases, at other sites in the body.

‘Acute hypoxia in tumors: implications for modifiers of radiation effects,’ describes methods that were developed in selecting and analyzing cells from tumors as a function of their distance from the tumor blood supply.

This information provides direct evidence that, at least for that tumor, hypoxia can result from transient fluctuations in blood perfusion.

There is evidence about the fast growth of tumors when the condition of hypoxia is present. ‘Microenvironmental and cellular consequences of altered blood flow in tumours’ gives credence to this notion, stating

...tumor angiogenesis is triggered by various signals characteristic of the tumor microenvironment, including low oxygen tension, low extracellular pH and low glucose concentration.

The abstract also draws a correlation between hypoxia and cancer metastasis:

Exposure to hypoxia either induces or selects for cells that are hyper glycolytic, and this in turn produces local acidosis which is also a common feature of solid tumors…Evidence linking tumor acidity with increased activity of several extracellular matrix-degrading enzyme systems is examined…High levels of lactate, another end-product of glycolysis, in primary lesions have been correlated with increased likelihood of metastasis...adoption of a hyper glycolytic phenotype is a necessary feature of carcinogenesis itself and confers a survival and proliferative advantage to tumor cells over surrounding normal cells. Empirical evidence supporting this "acid-mediated tumor invasion" model is discussed.

Additionally, ’Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma’ explores the relationship between tumor oxygenation and treatment outcome in human soft tissue sarcoma, claiming that tumor oxygenation predicts chances of cancer invasion.

...anaerobic culture of fibrosarcoma and melanoma cells followed by reoxygenation led to both significant DNA over replication and an increased level of distant metastases. Entry of hypoxic cells such as these into the systemic circulation and subsequent sequestration into the oxygen-rich environment of the lungs could explain the results of the present study…

Hypoxia can also affect cancer development, treatment, and prognosis according to ‘Regulation of Proliferation-Survival Decisions during Tumor Cell Hypoxia,’

Hypoxia may thus produce both treatment resistance and a growth advantage.

And in ‘Hypoxia and radiation therapy: Past history, ongoing research, and future promise’,

...changes in blood flow and oxygen consumption during the course of multi fraction and multi-agent therapy alter tumor oxygenation and are probably critical in determining the efficacy of many widely used therapeutic regimens.

In ‘Prognostic significance of tumor oxygenation in humans,

Low tissue oxygen concentration has been shown to be important in the response of human tumors to radiation therapy, chemotherapy and other treatment modalities. Hypoxia is also known to be a prognostic indicator, as hypoxic human tumors are more biologically aggressive and are more likely to recur locally and metastasize.

And lastly, in ‘Investigating hypoxic tumor physiology through gene expression patterns,’

Clinical evidence shows that tumor hypoxia is an independent prognostic indicator of poor patient outcome. Hypoxic tumors have altered physiologic processes, including increased regions of angiogenesis, increased local invasion, increased distant metastasis and altered apoptotic programs.

Based on the findings of the previously mentioned studies, the appearance, development, and metastasis of cancer can be attributed to cell hypoxia which can occur as result of extended hyperventilation. Therefore, the Wim Hof method may not be advantageous when included in a cancer-prone individual's "prevention plan" due to the potential risks involved with hypoxia (as a potential consequence resulting from the hyperventilation component of the breathing exercise).

Answer 3

The point about reduced hyperventilating leading to reduced oxygen/hypoxia, and subsequent extensive evidence provided with it, misses the point entirely! The method has been proven to increase the oxygen content and capacity of the blood not reduce it. Temporary hypoxia is part of the training process. You train by stressing something (be it muscle or mind) until it’s temporarily weakened. The result is a strengthening through discipline. To negate the benefits of the Win Hof method based on the negative effects of hypoxia is redundant.

Admittedly further studies are needed to verify potential benefits/dangers but the emerging evidence of the hugely positive effects this is having is certainly worth that study. I for one will be trying it myself as opposed to clinging to what we learned was correct. Our loyalty to societal and academic constructs is the biggest blight to progress. Don’t react with knee jerk scepticism! Read with an open mind and try yourself!