Wim Hof Method and the “E. coli confusion”

If you have a few seconds:

The E. coli endotoxin protocol is used to study the effects of an intervention, in this case the practice of the Wim Hof Method, on acute inflammation. It does not allow any conclusions to be drawn about infection control.

If you have a few minutes, keep reading…

I’ve been thinking about writing this post for a long time. Since I started practicing the Wim Hof Method, I have regularly seen a confusion that hurts the microbiologist in me, namely the confusion between “E. coli” and “E. coli endotoxin”. I have seen this confusion for years in articles, discussions on social media, and I hear it from students at my workshops. Unfortunately, this mistake seems to have taken hold in all layers of WHM practitioners, even at very high levels.

And this is very unfortunate, as we will see.

So I always spend some time during my workshops to undo this confusion. Indeed, the ever-increasing popularity of the WHM has been based not only on the charisma and exploits of its founder, but also on a series of scientific studies involving the injection of E. coli endotoxin. This E. coli endotoxin injection protocol was indeed used in the three studies on the effects of WHM on acute inflammation, conducted on Wim Hof or on cohorts of trained subjects (Kox et al., 2012; Kox et al., 2014; Kox et al., 2022).

Understanding this protocol is thus crucial to interpreting what science allows us to understand about WHM. This is of course the current state of knowledge and until proven otherwise, as science is a constantly evolving field.

Understanding this protocol is not a snobbery of a fussy expert. It is above all a matter of acquiring the right knowledge in order not to base one’s practice on beliefs whose consequences could be unfortunate. We will see why.

So, let’s go, in the three studies, the acute inflammation was induced by injection of an E. coli endotoxin. But what is an endotoxin? And to begin with, what is E. coli?

What is E. coli?

Bacteria are microscopic living organisms consisting of a single cell. As with all living things, bacteria are represented by different species. Behind the abbreviation E. coli is the full name of a bacterial species, Escherichia coli. It is a bacterial species very well known to microbiologists, probably the best known. It has the shape of a rod of a thousandth of a millimeter long. Historically, it has been found in abundance in the feces of mammals, both human and non-human, hence the species name coli – from the colon. The ease of finding and growing it under laboratory conditions soon made it a “laboratory model bacterium”. Later, such domestication allowed an incredible amount of (ongoing) discoveries on genetics, protein structure, genetic engineering etc. In microbiology, it is rare that we are satisfied with the species, we also like to look at the subspecies, or even the different strains of the same species. Thus, if our intestines are occupied by harmless strains of E. coli, there are also pathogenic strains. The harmless strains are part of our intestinal microbiota and can, for example, produce vitamin K-2 which is useful to us. On the other hand, pathogenic strains can cause food poisoning or urinary tract infections.

Here is a cool animation of E. coli cells escaping a macrophage…

So, now that you have mastered E. coli, let’s talk about its endotoxin.

The endotoxin is a bacterial extract. Many bacteria, including E. coli, have a barrier to the outside world composed of several layers: an inner membrane, surrounded by an intermediate mesh, itself surrounded by an outer membrane, itself covered by “decorations”. These are like a network of extensions attached to the outer membrane. They are composed of lipid and sugar molecules (polysaccharides)¹. This composition gives to this external envelope its name: lipopolysaccharides (LPS). This is the name found in scientific papers, including those concerning the WHM studies (Kox et al., 2012; Kox et al., 2014; Kox et al., 2022). The term LPS refers to the same thing as endotoxin. Endotoxin/LPS is a large molecule. It is not alive like a bacterium, and has no genetic material like a virus: it cannot multiply, and therefore is not infectious.

The diagram below gives a fairly accurate idea of the organization of the membrane of bacteria like E. coli. It shows the lipopolysaccharides (endotoxin/LPS). Because of their extension outside the cell, they are in the first line of encounter with the immune system, should the cell end up in the bloodstream of a host organism.

But then, what does the endotoxin injection protocol consist of?

The injection of endotoxin/LPS in the blood of the subjects causes an endotoxemia characterized by a systemic inflammation. This protocol has been used since the 1960s (Calvano & Coyle, 2012). It is commonly practiced by Radboud Medical University Center where the WHM studies of interest were performed. One of the characteristics of systemic inflammation is flu-like symptoms (headache, fever, back pain…) that the subject can report in a questionnaire. But researchers also have access to objective markers of inflammation: cytokines in the blood. These molecules are small proteins that allow cells to talk to each other from a distance and in particular to modulate the activity of the immune system. Inflammation is the activation of the innate immune system, the nonspecific part of the immune system, which goes into overdrive when an intruder is detected in the body. In addition, the activation of the innate immune system allows the mobilization of the other part of the immune system: the adaptive immune system, which will provide a specific response to the detected intruder.

A test for inflammation, not infection

The crucial point to remember is that this protocol does not inject an infectious agent, but only a bacterial extract incapable of infection. Thus, performed in a hospital setting, it is a safe and reproducible protocol for studying the effects of an intervention, in this case WHM, on acute inflammation. In these studies, it has been clearly shown that the practice of WHM decreases the effects of endotoxemia: less flu-like symptoms, less inflammatory cytokines, more anti-inflammatory cytokine. The practice of WHM on an infection has not been tested².

So, it is not true to say things like: “WHM practice kills infections, as proven by science”; “Science has proven that WHM can kill E. coli” or even “It is scientifically proven that WHM helps kill all infections including viruses”. The problem with these claims is that they are based on science that does not exist (yet). And so they misuse science to validate a belief. Maybe WHM can help better manage infections, but the actual science doesn’t allow to answer.

But then, why are these studies valuable anyway?

When I explain all of this to students, I sometimes see disappointed looks, as if I’m shattering a cherished hope of theirs. Once this confusion is over, I have seen people react by saying “but then why practice WHM?” Rest assured, there is no reason to stop practicing, even after this confusion has been cleared up!

– The current data thus concern the effect of WHM on the innate immune system and thus on inflammation. The researchers hypothesize in their articles that this practice could be interesting for people suffering from autoimmune diseases.

– Data on the effect of WHM on infections are currently lacking. In general, the benefits of WHM on the adaptive immune system are more speculative than robust. But absence of evidence is not evidence of absence. And it is possible that in the future new findings will point to a positive effect of WHM on infections. But in the meantime, there is no robust scientific reason to feel invincible.

– Beyond the immune system component, there are other – otherwise equally speculative but equally interesting – aspects that WHM addresses, such as stress management, mental health and mental preparation.

All of this gives good reasons to practice WHM if you think you need it or if you just want to do it. As long as you are playing with comfort and not with safety, there is no reason not to do it. In my opinion, spreading false beliefs based on a misunderstanding of scientific data has many drawbacks. The main one is that such beliefs about alleged total immunity can lead to dangerous behavior. Imagine people believing they are so immune to HIV that they would not even think of protecting themselves or their partners by using a condom. Then imagine the consequences of such behavior on public opinion, which would be tempted to classify this practice as a dangerous or even sectarian deviation. It would then take a long time to bring it back into the spectrum of acceptable practices and for scientists to look at it again. This is precious time that has been lost and that could have been better used to promote a reasonable approach in order to help a maximum number of people.

In short, this confusion of “E. coli” and “E. coli endotoxin” is not a detail elaborated by one of those boringly picky microbiologists. This confusion has direct consequences on the practice and credibility of WHM.

🔥❄️🧠✌️

Sébastien.

¹ For those who want more details, it is the structure of the wall of the so-called Gram-negative bacteria: an internal lipid membrane, surrounded by a peptidoglycan mesh, itself surrounded by an external lipid membrane covered by a lipopolysaccharide envelope.

² In this regard, I am not a specialist in clinical microbiology, let alone human trials. But I do know that this type of research is highly supervised with bioethics committee. Injecting an infectious agent into human subjects is not trivial research.

References :

Calvano SE, Coyle SM. Experimental human endotoxemia: a model of the systemic inflammatory response syndrome? Surg Infect (Larchmt). 2012 Oct;13(5):293-9. doi: 10.1089/sur.2012.155. Epub 2012 Oct 16. PMID: 23072275; PMCID: PMC3503465.

Kox M, Stoffels M, Smeekens SP, van Alfen N, Gomes M, Eijsvogels TM, Hopman MT, van der Hoeven JG, Netea MG, Pickkers P. The influence of concentration/meditation on autonomic nervous system activity and the innate immune response: a case study. Psychosom Med. 2012 Jun;74(5):489-94. doi: 10.1097/PSY.0b013e3182583c6d. PMID: 22685240.

Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FC, van der Hoeven JG, Pickkers P. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc Natl Acad Sci U S A. 2014 May 20;111(20):7379-84. doi: 10.1073/pnas.1322174111. Epub 2014 May 5. PMID: 24799686; PMCID: PMC4034215.

Kox M et al. 2022. Accepted for publication.