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Wim Hof Method Research Paper

Exclusion criteria were: febrile illness during the 2 wk before the endotoxemia experiment, taking any prescription medication, history of spontaneous vagal collapse, practicing or experience with any kind of meditation, or participation in a previous trial where LPS was administered.
Table 1: Subject demographic characteristics (Kox. 2014).
The subjects were randomly allocated to the trained group (n = 18) or the control group (n = 12) by the opening of a sealed envelope prepared by a research nurse not involved in the study. After having fulfilled the training program, 12 of the 18 trained subjects were randomly assigned to participate in the experimental endotoxemia experiments (see Figure 1).

The study itself (which excluded several of the originally 30 subjects, because their reaction to endotoxemia, i.e. the influx of  (potentially) pathogenic metabolic byproducts of bacteria into their blood was "odd" (i.e. too extreme as in too low or too high) was sequentially conducted in two identical blocks, each consisting of nine subjects in the trained group (of which six finally participated in the endotoxemia experiments) and six subjects in the control group. As the authors point out,
"[...t]his design was chosen to minimize the bias due to differences in the interval between the end of the training period and the endotoxemia experiments. As the aim of [their] study was to investigate the effects of the training intervention on the innate immune response in a standardized model of systemic inflammation, [they] did not assess the effects of the training intervention on immune system parameters in the absence of endotoxemia" (Kox. 2014). 
A schematic overview of the study design (one block) is depicted in Fig. S3. The trained group was trained by Dutch individual Wim Hof and three trainers who previously received an instructor course by Wim Hof to become a trainer. A medical doctor of the study team (L.T.v.E.) and the principal investigator (M.K.) were present during all training sessions (in Poland and in The Netherlands), and during the experimental endotoxemia experiments. The first 4 d of the training program took place in Poland and were most intensive.
The Internet is full of praise for Hof's method, but that's not scientific eviden-ce (infographic from therenegade-pharmacist.com)... it does show that Hof is a good marketer, though ;-)
What did the program look like? The program consisted of three main elements: meditation, exposure to cold, and breathing techniques. (i) Meditation: so-called “third eye meditation,” a form of meditation including visualizations aimed at total relaxation. (ii) Voluntary cold expo-sure: standing in the snow barefoot for up to 30 min and lying bare chested in the snow for 20 min; daily dipping / swimming in ice-cold water (0–1 °C) for up to several minutes (including complete submersions); and hiking up a snowy mountain (elevation: 1,590 m) bare chested, wearing nothing but shorts and shoes at temperatures ranging from −5 to −12 °C (wind chill: −12 to −27 °C).

(iii) Breathing techniques,
consisting of two exercises: in the first exercise subjects were asked to hyperventilate for an average of 30 breaths. Subsequently, the subjects exhaled and held their breath for ∼2–3 min (“retention phase”). The duration of breath retention was entirely at the discretion of the subject himself. Breath retention was followed by a deep inhalation breath, that was held for 10 s. Subsequently a new cycle of hyper/hypoventilation began. The second exercise consisted of deep inhalations and exhalations in which every inhalation and exhalation was followed by breath holding for 10 s, during which the subject tightened all his body muscles. These two breathing exercises were also performed during the endotoxemia experiments. Additional element of the training program consisted of strength exercises (e.g., push-ups and yoga balance techniques).
After returning from Poland, the subjects practiced the techniques they learned daily by themselves at home (2–3 h/d; cold exposure was achieved through taking cold showers) until the endotoxemia experiment day (5–9 d later).
Figure 1: Study design. This block was carried out twice in identical fashion, resulting in 12 subjects in both groups that underwent experimental endotoxemia. CT, control subject; TR, trained subject (Kox. 2014).
After training the method at home, all subjects returned to the lab, where a final group training took place and at the end of this day, six of the nine trained subjects (in each block) were randomly selected for participation in the endotoxemia experiments, using the sealed envelope method. Then, ...
"[...t]he selected subjects practiced in a final training session led by Wim Hof on the day before the endotoxemia experiment day. Wim Hof was present to coach the subjects during the endotoxemia experiment days during the 3 h that the subjects in the trained group practiced the learned techniques. The control group did not undergo any training procedures throughout the study period" (Kox. 2014).
To evaluate the effect of Hof's method on the subjects' immune system, the subjects, who had refrained from caffeine- or alcohol-containing substances 24 h before the start of the experiment, and food 10 h before the start of the endotoxemia experiment, were injected purified lipopolysaccharides from Escherichia coli, which were supplied as a lyophilized powder that was reconstituted in 5 mL saline 0.9% for injection and vortex mixed for at least 20 min after reconstitution.
Figure 2: Cardiorespiratory parameters, temperature, and symptoms (A-I), as well as plasma
cathecholamine concentrations and serum cortisol concentrations during experimental endotoxemia
in control (dotted line) and trained (solid line) subjects (J-M | Kox. 2014).
As the scientists point out, "[t]he LPS solution was administered as an i.v. bolus injection at a dose of 2 ng/kg body weight in 1 min at T = 0 h (Kox. 2014). More specifically, ...
"[...a] cannula was placed in an antecubital vein to permit infusion of 0.9% NaCl solution; the subjects received 1.5 L 0.9% NaCl during 1 h starting 1 h before endotoxin infusion (prehydration) as part of our standard endotoxemia protocol (29), followed by 150 mL/h until 6 h after endotoxin infusion and 75 mL/h until the end of the experiment" (Kox. 2016).
To estimate the effect of the breathing techniques, the authors measured not just cardiorespiratory parameters, temperature, and symptoms, but also the levels of catecholamines, cortisol and plasma cytokines (stress), as well as the leukocyte count (immune reaction) and conducted correlation analyses of all these variables.
Figure 3: Plasma cytokine concentrations during endotoxemia in control and trained subjects. (A, C, E, and G) Median values of pro- (TNF-α, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines (n = 12 per group). (B, D, F, and H) Median ± interquartile range of area under curve (AUC) of pro- (TNF-α, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines (n = 12 per group; unit: ×104 pg/mL·h). P values were calculated using Mann–Whitney u tests (Kox. 2014).
The results are - initially (eventually, it's a normal stress response, see Bottom Line)- quite astonishing, as the "intervention group, practicing the learned techniques" (Kox. 2014) didn't just show symptoms of being suffocated, i.e. am intermittent respiratory alkalosis and hypoxia resulting and corresponding increases in the levels of the stress hormones epinephrine in the blood, but also ...
  • Figure 3: Correlation analysis (Kox. 2014).
    significant increases of the anti-inflammatory cytokine IL-10, which correlated strongly with the preceding increase in epinephrine levels (see Figure 3A), as well as
  • significant reductions of the proinflammatory mediators TNF-α, IL-6, and IL-8, which, in turn, correlated negatively with IL-10 levels.
In conjunction with the significant reduction of "flu-like symptoms", the scientists observed in the intervention group, the study at had does therefore in fact "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" (Kox. 2015).
Wow! This really works!? Yes, the study at hand confirms that the long-held theory that both, the autonomic nervous system and innate immune system, cannot be voluntarily influenced must be considered disproven - the "Wim Hof Method", of which the authors of the present paper highlight that it consists of techniques that can be "learned in a short-term training program" (Kox. 2014) seems to do what scientists have long considered impossible: it allows people like you and me to directly influence their sympathetic nervous system and immune system in a way that triggers highly pronounced increases in the stress hormone epinephrine and down-stream immune effects in form of increases of the production of anti-inflammatory mediators and a subsequent dampening of the proinflammatory cytokine response to an (albeit artificial) immune challenge with bacterial endotoxin.

Believe it or not, but an intense workout will have pretty much the same effects on inflammation (in this case triggered by the workout itself) as the "unique" Hof Method (figure from Petersen. 2005; expanded). A study that evaluates the conditioning effect in the same endotoxin model has yet, as far as I know, still to be done.
As Kox et al. point out, their 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" (Kox. 2014). Before these benefits have scientifically proven, though, I would like to remind you that exercise can induce similar increases in epinephrine, subsequent increases in IL10 and corresponding decreases of various inflammatory cytokines (Brandt. 2010, Petersen. 2005 & 2006; just as simply injecting or increasing epinephrine by other means will | Van Der Poll. 1997), albeit in response to exercise alone, not in response to endotoxin exposure. Whether the response to this stressor would be similarly conditioned and would thus affect endotoxin assaults, has imho not been investigated | Comment!
References:
  • Brandt, Claus, and Bente K. Pedersen. "The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases." BioMed Research International 2010 (2010).
  • Kox, Matthijs, et al. "Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans." Proceedings of the National Academy of Sciences 111.20 (2014): 7379-7384.
  • Pedersen, Bente Klarlund, and Laurie Hoffman-Goetz. "Exercise and the immune system: regulation, integration, and adaptation." Physiological reviews 80.3 (2000): 1055-1081.
  • Petersen, Anne Marie W., and Bente Klarlund Pedersen. "The anti-inflammatory effect of exercise." Journal of applied physiology 98.4 (2005): 1154-1162.
  • Petersen, A., and B. Pedersen. "The role of IL-6 in mediating the anti inflammatory." J Physiol Pharmacol 57 (2006): 43-51.
  • Van Der Poll, Tom, and Stephen F. Lowry. "Epinephrine inhibits endotoxin-induced IL-1β production: roles of tumor necrosis factor-α and IL-10." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 273.6 (1997): R1885-R1890.

Dutchman Wim Hof earned his nickname ‘The Iceman’ for his world records involving the cold – standing for almost two hours in a crate full of ice cubes, that sort of things. But in recent years he is promoting the methods that he claims enabled him to achieve these records as a method for achieving better health as the ‘Wim Hof Method’. Already he has gained a lot of enthusiastic followers and he has been training many people to propagate his method.

On this website I have written about Hof before, not directly about his method, but about a promotional stunt a year ago which didn’t go as well as he wanted the world to believe: his group climbing of Kilimanjaro in the ‘record time’ of 31 hours didn’t reach upto the actual summit (read  ‘Iceman’ Wim Hof over the top‘).

For Skepter, the magazine of Dutch skeptics foundation Skepsis, I was asked to write an article about Hof and his method. In this article I focused more on the scientific evidence for the many claims surrounding the Wim Hof method. Luckily I could base my article on the book Hof published in spring last year which precisely claims to give the state of scientific evidence for his method from his point of view: ‘Koud Kunstje – Wat kun je leren van de Iceman?’ by Wim Hof & Koen de Jong (april 2015) [translates as: Cold trickery – What can we learn from the Iceman?].

The article I wrote for the August editon of Skepter can be read online on the Skepsis website (Dutch):  Bergop, bergaf met The Iceman – De Wim Hof methode. I will give a summary here, but if you have questions about the original article and you have trouble understanding the Dutch text, feel free to leave your questions in the comments.

The science

The Wim Hof Method is a combination of three things: exposure to cold, breathing techniques and meditation. The cold exposure is the most visible part of the method, especially when people step into bathtubs filled with ice cubes. Hof’s ability to withstand long exposure to cold has been researched and is partially explained because he has larger than usual amounts of brown fat on his body. His twin brother André (with similar brown fat amounts) also showed the bigger capability to endure the cold, without being trained in the breathing techniques Hof uses (research bij prof. Van Marken Lichtenbelt, Maastricht University – published in PLOS ONE, 2014).

The breathing  and meditation are based on Tibetan Tummo techniques, which spiritual aspects were stripped off by Hof for his method. The breathing Hof promotes comes down to repeatedly taking 30 deep breaths in a row, followed by keeping your breath for as long as you can. In this way you cause hyperventilation. A good thing according to Hof in his book, because that would lead as much oxygen as possible deep into your cells, enabling your mitochondria to produce more energy, unwanted rest products from processes in your body being cleaned up, and also prevent the production of lactic acid. You will even feel better according to Hof, because his techniques get more oxygen to the pineal gland, which then starts to produce more melatonine.

At the Radboud University Medical Center in Nijmegen several researchers investigated the physical capabilities of Hof. They found out that Hof is able to show some control over his immune system, which was not thought possible. The most important scientific result for Hof came in 2014 with the publication of Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans, Kox, Pickkers et al. (PNAS, 2014). In this research twelve healthy volunteers were trained in the Wim Hof Method and twelve others were not. They all got an injection of an endotoxin from the Escherichia coli bacteria. Normally the body reacts quite vehemently to this, but the trained volunteers were able to keep the body’s reaction at a far lower level than their untrained counterparts. Kox and Pickkers think that this is mostly caused by the breathing technique:

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.

In lay terms: the hyperventilation reduces the normal response of the body to the endotoxin. This would not  be generally worthwhile, because the body is now acting less aggressive against the invasion of something it wants to get rid off. But there are cirumstances where this might be actual beneficial. However, whether this is anything more than an interesting scientific fact remains to be seen. Pickkers and Kox emphasize that this experiment was done with healthy volunteers and has only proven that a short term effect can be obtained. Suggesting that this might lead to an effective treatment for people who suffer from an overacting immune system is pure speculation.

The quackery

Strange thing about this book is that the authors give attention to other methods as well, which don’t really have a link with the Wim Hof Method and are clearly nonsense. Most likely this interest comes from Hof’s co-author De Jong (a former pro-cyclist turned running coach), who has connections with people who have written or practice these methods. One such method is the Buteyko Breathing Technique, which like the Wim Hof Method promotes a specific way of breathing, but is based on a totally different theory. And that theory is utterly flawed. There is a nice article on Science Based Medicine by Joseph Albietz on this: Buteyko Breathing Technique – Nothing to Hyperventilate About.

The other obvious bullocks is earthing. Wim Hof hasn’t said anything about this before this book came out. He walks barefooted a lot of the time, but never associated this with earthing as far as I know. Earthing is based on the bizarre idea that we need to give electrons from the earth easier access to our body, because these are needed to neutralize free radicals there. But you can better read what Steven Novella wrote about earthing. Also David Servan-Schreiber is mentioned in the book, who promoted all kind of dubious alternative treatments against cancer.

In my opinion the attention given to these silly theories undermines the serious scientific attitude Wim Hof claims to pursue for his own methods. There seem to be a lot of people surrounding Hof who are willing to jump the bandwagon to promote their own ideas, which do not really have anything in common with the Wim Hof Method. I’m not sure why Hof lets this happen, but I guess he is just happy with all attention which looks like it supports his own ideas.

One other person is making an appearance in this book as a Wim Hof supporter: former professor Pierre Capel. He is speculating a lot on the working mechanism underlying the effect Pickkers and Kox have shown. Something about transcription factors which can be influenced with mediation. And he makes quite bold claims of the possibilities of this for curing cancer. To me his ideas sound an afwul lot like the pseudoscientific ideas of Deepak Chopra. Capel left the professorship he held at Utrecht University in 2002, only 56 years of age, which is rather peculiar. After ‘retiring’ he hasn’t published any scientific article and only seems to promote yoga and meditation, so I would be very careful to take the ideas of this man too seriously.

False hope?

I guess that most people who are critical of Hof (or even call him a quack) are worried that he gives false hope to patients with serious diseases. Although Hof is aware of this and states in his book that he definitely doesn’t want to do this, it is hard not to get the impression that Hof has difficulties to keep his enthusiasm and optimism about the possible effects of his methods restrained. A good illustration of this is the following part of an interview he gave to regional television station Limburg 1 (L1) on May 20th 2014, shortly after the Pickkers and Kox study was published:

L1: ‘Are you convinced that someone with cancer can cure himself with these methods?’
Hof: ‘No, absolutely not, I would not go that far. What this is about … we have shown now, as the first group in the world, that the autonomic nervous system, of which science upto now was telling that you aren’t able to influence it, we can influence this in relation to the immune system. This means that every human from this moment on, can influence his autonomic nervous system in relation to his immune system and can learn to do this in really short time.
L1: ‘But Ockels thought …’ [PvE: Wubbo Ockels, the first Dutch astronaut, died of cancer just two days before the interview. He had shown much interest in the Wim Hof Method as one of the many alternative methods he tried out to beat the terminal cancer he was suffering from]
Hof: ‘This is what we have achieved at this moment. And science is above speculation, it is not philosophizing.’
L1: ‘I just asked you: can you cure cancer with these methods?’
Hof: ‘I believe that every disease, any disease whatsoever, is essentially a disbalance of the immune system and that this immune system …’
L1: ‘But do you claim that even cancer can be beaten with these methods?’
Hof: ‘Yeah, but proper research is necessary for this.’
L1: ‘OK that’s clear, it has not yet been proven, but you think it is possible?’
Hof: ‘I think absolutely that there, uh .. 95 percent of all diseases, amongst which are numerous types of cancers, can be cured.’

So far my impression of the Wim Hof Method is not too bad and I would really hesitate to call it quackery. The method doesn’t look that dangerous when performed in the presence of others (if you are alone, there might be some risks of falling when passing out performing the breathing exercises) and you can hardly find reports of bad experiences [see update]. Furthermore, it is quite cheap. Hof isn’t selling expensive stuff, just workshops which don’t seem overly expensive to me. Also he is not explicitely promoting his methods to sick people. Whether patients start using the Wim Hof Method, because of false hope he gives, is up for debate. I surely would like to see Hof more careful on this matter than he has been in the past.

More on the Kilimanjaro expedition

The Kilimanjaro expedition of 2015 didn’t go as well as the company of Hof (Innerfire.nl) was trying to let the world believe in their press release as I had set out in January last year (‘Iceman’ Wim Hof over the top). In Koud Kunstje the expediton is also mentioned and in the book Hof corrects the claim that they reached the summit in almost the same words as he used on Twitter to answer my question. However on Kloptdatwel.nl (the website on which I had written the original Dutch version of that blog), we were contacted by one of the participants of this expedition who told us that the expedition had been even far less succesful than we had already reported. Not only had a lot of the participants who didn’t make it to the edge of the crater shown clear symptoms of altitude sickness, but a big part of the group had to be evacuated off the mountain by car because of their poor physical condition. Among those Wim Hof himself, who had been exhausted and had been suffering from injuries to his feet.

I checked this story carefully with a couple of other participants, who confirmed this version of the story, before contacting Hof’s company. Hof and his son Enahm were not willing to indicate specific flaws in the reconstruction, but offered to talk about ‘the context’ on a cup of coffee. I didn’t pick up this invitation, because I felt I had given them ample opportunity to tell their side of the story. I published the reconstruction on Kloptdatwel: Bergaf met Wim Hof (Going down with Wim Hof). These blogs of mine probably set some bad blood between the Hofs and me. This became more clear on Facebook later, on a totally unrelated issue, where I was called a lousy journalist and even accused of using hate speech by Enahm. But when my article from Skepter was published online and he had actually read it, he even shared it via the Facebook page of Innerfire. Not that they apologized in any way, but at least this shows that they are not totally allergic to sound criticism.

Update 4-7-2016
Recently a couple of reports have appeared in newspaper Het Parool (1,2) on deaths by drowning probably caused by using the Wim Hof Method in an inappropriate way. Four men had been practicising the breathing techniques just before a long swim under water. This is extremely dangerous, because of the risk of ‘shallow water blackout‘. Wim Hof tells he and his company Innerfire have always warned for this risk during their workshops and on the Internet, but questions remain whether they have actually always given it the attention it needs.

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