The 'Wim Hof Method' - Effective? What Science Can Tell Us

The 'Wim Hof Method' - Effective? What Science Can Tell Us

anti-inflammatory destress health immune health immune system inflammation stress the hof method wim hof wim hof method

If someone markets his program the way Hof does, i.e. as a means to "Become A 'Super' Version Of Yourself In Just 10 Short, Life Transforming Weeks" (WimHofMethod.com), you should rightly be skeptical.

You know that I am no fan of "works for me (N=1), so buy my e-book"-approaches. Until recently, the so-called "Wim Hof Method" was yet exactly that: an N=1 (+ dubious X) approach to health and performance enhancement... and yes, that is "until recently", or rather "until two years ago", because two years ago, Matthijs Kox and colleagues from the Nijmegen Institute for Infection, Inflammation and Immunity, the Radboud University (will wonders never cease) the Yale University School of Medicine (Kox. 2014) published a study with the not so telling title "Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans" in the peer-reviewed scientific journal PNAS.

The study used a parallel randomized controlled design and was registered at ClinicalTrials.gov as NCT01835457. After approval by the local ethics committee of the Radboud University Nijmegen Medical Centre (CMO 2012/455), 30 healthy, nonsmoking, Dutch male volunteers were included in the trial.

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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.

Want to Home-Brew Your Own 15x More Bioavailable Super-Curcumin? Buy Buttermilk and a Yogurt Starter Culture

Want to Home-Brew Your Own 15x More Bioavailable Super-Curcumin? Buy Buttermilk and a Yogurt Starter Culture

anti-diabetes anti-inflammatory bioavailability cancer curcumin diabetes diabetsity health

No one says you cannot add other ingredients to the yogurt to make it more tasty if you add the curcumin before fermenting the buttermilk.

If you're a regular at the SuppVersity you will know that curcuminoids, the polyphenols found in turmeric roots (Curcuma longa), have health effects that are similar, in some cases even superior to several anti-inflammatory, anti-diabetic and lipid-lowering drugs. Yes, their consumption has even been linked to significant reductions in cancer risk. Unfortunately, there's a problem with these powerful polyphenols: they are hydrophopbic (Tønnesen. 2002) and prone to degradation in an aqueous environment at neutral and alkaline pH (Tønnesen. 1985; Wang. 1997) - two properties of which Gupta and others (2013) believe that they are responsible their poor oral bioavailability.

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Low bioavailability or not, Shishan Fu and rightly highlight in the introduction of their latest paper, even the hardly absorbed "regular" curcuminoids have been reported to offer many health-promoting properties (Gupta and others 2013), it is thus only logical that there's an "interest in the development of functional foods containing these compounds is increasing" (Fu. 2016).

Figure 1: Even dispersing them in buttermilk will increase the bioavailability by decreasing the breakdown of curcuminoids during digestion - that's at least what a 2014 study by Fu et al. shows. 

Hitherto scientists have (more or less successfully) tried to increase the solubility and stability of curcuminoids by dispersing them in matrices such as lipid-based emulsions (Ahmed. 2012; Yu and Huang. 2012), modified starch (Yu and Huang 2010), hydroxypropyl methyl cellulose (Chuah. 2014), milk proteins (Yazdi and Corredig. 2012), and buttermilk (Fu. 2014). As Fu et al. point out, ...

"[...t]he bioavailability may also be increased when formulated in appropriate delivery systems. For example, lecithin–piperine formulations containing curcuminoids and curcuminoids encapsulated in cellulose have been reported to have enhanced bioavailability after oral administration in humans (Antony and others 2008; Vitaglione and others 2012)" (Fu. 2014).

Based on their own previous study with regular buttermilk and evidence that yogurt can significantly increase the stability and bioavailability of bioactives, like green tea polyphenols (Lamothe and others 2014), Fu et al. speculated that dispersing curcuminoids in buttermilk prior to yogurt manufacture would exert even more powerful effects than simply mixing them with buttermilk (see Figure 1). To test this hypothesis, the scientists did something anyone of you can do at home (see Figure 2 for information on how the control samples were prepared, too):

Figure 2: Preparation of yogurts (Fu. 2016).

"A buttermilk dispersion (14% total solids, w/w) was prepared by reconstituting 142.3 g of buttermilk powder in MilliQ-water which was made up to 1000 g. The powder was dispersed in the water at 45 °C with stirring using an overhead stirrer (Heidolph RZR 2051 control, Germany) at 1000 rpm for 30 min. The dispersion was then stored at 4 °C overnight for more complete hydration. The chosen fortification level of curcuminoids in yogurt was 300 mg/ 100 g yogurt (0.3% w/w)

An ABT-5 culture was prepared by mixing 0.2 g of culture granules in 10 mL of buttermilk dispersion (14% total solids, w/w) and stirring for 15 min in an ice bath. This culture solution was prepared freshly prior to fermentation. The ABT-5 culture was added at a level of 0.2 g/L of yogurt buttermilk. The buttermilk was subsampled (50 mL) into separate plastic containers and incubated at 43 °C until pH reached 4.6. These set yogurts were put into the ice water bath for 30 min, stirred at 200 rpm for 20 s using a mixer (Heidolph RZR 2050, Germany) and then stirred manually (approximately 20 times) to obtain a uniform product. The stirred yogurts were stored in a cool room (4 °C) overnight. All analysis was completed within 2 d of yogurt manufacture. The total solids of the yogurts were estimated using a moisture analyser (Sartorius AG, Germany)." (Fu. 2016).

To be able to tightly control the experiment, the curcumin enhanced yogurt and the other samples were exposed to in vitro digestion. During this procedure, the sample (5 g) was mixed with 15 mL of simulated gastric fluid (SGF) containing 2 g NaCl and 7 mL 37% w/v HCl per liter (pH 1.23) and 3.2 mg/mL pepsin, and incubated in a water bath with 100 rpm at 37 °C for 2 h (United States Pharmacopeia Convention 2009).

"After exposure to SGF, the mixture was adjusted to pH 6.5 using 1 M NaOH and mixed with 9.6 mL of simulated intestinal fluid (SIF) containing 3 mL of 2 M NaCl, 0.3 mL of 0.075 M CaCl2, and 6.3 mL of 36.5 mg/mL bile extract in 5 mM phosphate buffer. The pH was adjusted to 6.8 and then 5.4 mL of 10 mg/mL pancreatin in phosphate buffered saline was added. Samples were incubated at 37 °C, 100 rpm for 3 h and then placed in an ice bath to arrest the enzyme activity. At the end of the in vitro digestion period curcuminoids were extracted from the whole digested mixture with acetone and quantified using HPLC-DAD" (Fu. 2016). 

The in-vitro digestion, which is described in a previous paper by Fu et al. (2015), provided the scientists with an estimate of the amount of undegraded curcuminoids - it is yet not a 100% reliable method to determine the real world biological effects in humans, which would have to be tested in future studies. In view of the fact that the scientists calculations show that the resistance of the curcuminoids to degradation after sequential exposure to SGF and SIF improved more than just statistically significantly (see Figure 3), it is logical to assume that benefits would be observed in vivo, too.

Figure 3: Bioaccessibility of curcuminoids after sequential exposure of samples to SGF and SIF (Fu. 2016).

The difference pre-processing, i.e. the prior dissolution in ethanol (which wouldn't make you drunk, anyway, because the total ethanol content of the yogurt would be marginal), the dissolution of curcuminoids in buttermilk and its fermentation to "curcumin enhanced" buttermilk yogurt with a standard ATB yogurt starter culture, made in terms of the bioavailability is after all huge.

In fact, the bioavailability of the curcuminoids increased to an extent that easily surpasses the hyped BCM-95®, a combination of curcumin and bioperin, which has been shown to exhibit a 6.93-fold higher bioavailability. In all fairness, we shouldn't forget, though, that, unlike the yogurt trick described here, Biocurcumax™ has already been studies in humans (Antony. 2008).

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The total bioavailability is still low, but... As, Fu et al. point out in the conclusion of their soon-to-be-published paper, "[t]he most important and practical finding from the bioaccessibility data is that the incorporation of powdered curcuminoids into buttermilk prior to yogurt manufacture results in a 15-fold increase in bioaccessibility of curcuminoids compared to that of neat curcuminoids dispersed in aqueous buffer" (Fu. 2016).

The scientists are yet also right to point out that even with the enhanced bioaccessibility of curcuminoids the total bioavailability was still low (approximately 6%) when they were delivered in yogurt.

In view of the fact that the polyphenols which are transferred into the colon are degraded by gut microflora and the degradation products contribute to the bioactivity of these compounds in the body, the real-world relevance of this astonishing increase in bioavailability will have to be tested in in vivo, before we can have a final say on the practical significance of these findings | Comment!

References:

• Ahmed, Kashif, et al. "Nanoemulsion-and emulsion-based delivery systems for curcumin: encapsulation and release properties." Food Chemistry 132.2 (2012): 799-807.
• Antony, B., et al. "A pilot cross-over study to evaluate human oral bioavailability of BCM-95® CG (Biocurcumax™), a novel bioenhanced preparation of curcumin." Indian journal of pharmaceutical sciences 70.4 (2008): 445.
• Chuah, Ai Mey, et al. "Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin." Food chemistry 156 (2014): 227-233.
• Fu, Shishan, et al. "Bioaccessibility of curcuminoids in buttermilk in simulated gastrointestinal digestion models." Food chemistry 179 (2015): 52-59.
• Fu, Shishan, e al. "Enhanced Bioaccessibility of Curcuminoids in Buttermilk Yogurt in Comparison to Curcuminoids in Aqueous Dispersions." Journal of Food Science (2016): Ahead of print. doi: 10.1111/1750-3841.13235
• Yazdi, S. Rahimi, and M. Corredig. "Heating of milk alters the binding of curcumin to casein micelles. A fluorescence spectroscopy study." Food Chemistry 132.3 (2012): 1143-1149.
• Yu, Hailong, and Qingrong Huang. "Enhanced in vitro anti-cancer activity of curcumin encapsulated in hydrophobically modified starch." Food Chemistry 119.2 (2010): 669-674.
• Yu, Hailong, and Qingrong Huang. "Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions." Journal of agricultural and food chemistry 60.21 (2012): 5373-5379.