up:: [[Wim Hof Method]] tags:: #on/health #on/hormesis #note/develop # WHM Science These are my highlighted notes from reading research papers, there are ongoing research which are listed on the official [Wim Hof Method Science](https://www.wimhofmethod.com/science) webpage. Some of the content on this page may be quite technical. For an overview, I personally enjoy [[Practical Sides of WHM Science]] as explained by [[Dominique Stulens]]. The greatest value for these notes is that I have mapped [claims and benefits](https://www.wimhofmethod.com/benefits#mental-benefits) of the method to where I have looked up the scientific literature and internalized the information. It's a great reference document to help me find resources when explaining why the [[WHM Mechanics]] work. If a research article is not listed here yet, it just means that I have not analyzed/internalized it myself. I welcome collaborations with other practitioners, if you see a gap or inaccuracy on my notes, reach out on my [Discord Server](https://discord.gg/UC349RFKg2). > Note: Research summaries generated with [[SciSpace]] then lightly edited. Benefits were explored with [[SciSpace#Copilot]] for scientific rigor. ## WHM Benefits ###### Boost the immune system - These techniques are believed to induce a state of hyperventilation, leading to a decrease in carbon dioxide levels and an increase in blood pH. - Alkaline conditions have been shown to promote the activity of immune cells and increase their ability to fight off pathogens. - Increased blood alkalinity, or a higher pH level, has been associated with various physiological effects, including improved oxygen delivery to tissues and enhanced immune function. - [[Cold Exposure]] stimulates the production of white blood cells, such as lymphocytes and natural killer cells, which play a crucial role in immune defense. - Cold exposure enhances the activity of immune cells by increasing their mobility and ability to recognize and destroy pathogens. - Cold exposure improves the function of dendritic cells, responsible for initiating immune responses by presenting antigens to other immune cells. - The immune-enhancing effects of cold exposure may benefit individuals with compromised immune systems, such as cancer patients undergoing chemotherapy. ###### Increase energy levels - The combination of cold exposure, breathwork, and meditation in WHM has been shown to activate the sympathetic nervous system, leading to increased alertness and energy levels. - The breathwork component of WHM involves specific breathing techniques that can increase oxygen intake and improve oxygen delivery to tissues. - WHM has been reported to improve mitochondrial function, which is responsible for energy production in cells, potentially leading to increased energy levels. ###### Relieve stress and anxiety * The combination of cold exposure, breathwork, and meditation in WHM has been shown to activate the parasympathetic nervous system, leading to a relaxation response and reduced stress level. * WHM has been reported to increase the release of [[Endorphins]], which are natural painkillers and mood enhancers, contributing to a sense of well-being and reduced anxiety. ###### Reduce inflammation * WHM has been shown to activate the [[Sympathetic Nervous System (SNS)]], leading to the release of adrenaline and noradrenaline, which can have anti-inflammatory effects. * WHM has been associated with increased production of anti-inflammatory [[Cytokines]] and decreased production of pro-inflammatory cytokines, indicating a potential modulation of the immune response. * WHM has also been reported to increase the production of heat shock proteins, which have anti-inflammatory properties. ###### Improve circulation - WHM involves cold exposure, which has been shown to constrict blood vessels and increase blood flow when the body warms up again, potentially improving circulation. - WHM has been associated with increased production of nitric oxide, a molecule that helps dilate blood vessels and improve blood flow. - WHM has also been reported to improve cardiovascular function, including increased heart rate variability and improved [[Endothelial]] function, which can contribute to better circulation. ###### Enhance cognitive and physical performance - WHM has been associated with improved focus, concentration, and mental clarity, potentially enhancing cognitive performance. See [[#Relieve stress and anxiety]]. - WHM involves specific breathing techniques that can increase oxygen intake and improve oxygen delivery to tissues, which can enhance physical performance. - WHM has been shown to activate the sympathetic nervous system, leading to increased adrenaline and noradrenaline release, which can improve physical performance. ###### Influence the body's autonomic nervous system * See [[#The Radboud Study - Voluntary Activation of The Sympathetic Nervous System and Attenuation of the Innate Immune Response In Humans (2014)](https //media-cdn.wimhofmethod.com/uploads/kcfinder/files/PNAS.pdf)]] ###### Manage autoimmune diseases * See [[#"Battling Arthritis" — An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis - A proof of concept trial (2019)](https //www.wimhofmethod.com/blog/battling-arthritis)]] ###### Increase your happiness and sense of well-being - WHM has been shown to increase the production of certain [[Neurotransmitters]], such as [[Dopamine]] and [[Serotonin]], which can impact mood and emotional regulation, both of which are regulated by the autonomic nervous system. ## Research Articles ###### [The impact of a focused behavioral intervention on brain cannabinoid signaling and interoceptive function: Implications for mood and anxiety (2023)](https://www.sciencedirect.com/science/article/pii/S294983412300034X "Article: The impact of a focused behavioral intervention on brain cannabinoid signaling and interoceptive function: Implications for mood and anxiety") **TL;DR** - The study investigated the effects of the Wim Hof method (WHM) on the brain. - WHM intervention led to an increase in CB1 receptor binding in the brain. - Participants showed increased engagement of brain regions associated with interoceptive and executive functions. - The results suggest that WHM positively impacts stress resistance, mood, anxiety, and interoceptive function. **Results** - Longitudinal WHM intervention increased CB1 receptor binding by ~20%. - Largest increases in CB1 receptor binding in interoceptive brain regions. - WHM intervention positively impacted brain markers associated with stress resistance, mood, anxiety, and interoceptive function. **Methods Used** - Longitudinal (6 weeks) Wim Hof method (WHM) intervention. - Deep breathing exercises, cold exposure, and meditation. - F18]FMPEP-d2 PET tracer to measure CB1 receptor binding. - Whole-body cold-stress paradigm to evoke sympathetic and parasympathetic responses. - fMRI to investigate acute changes in brain sub-network activity. - PETCT imaging to investigate long-term changes in CB1 receptor binding. **Limitations** - Small sample size (n=4) due to demanding time commitments. - Exclusive inclusion of males compromises generalizability. - Lack of a placebo arm and inability to distinguish alternative explanations. - Inability to determine the necessity and sufficiency of WHM components. **Practical Implications** - WHM intervention leads to increased CB1 receptor binding in the brain. - WHM may improve mood and anxiety-related symptoms. - WHM could be an alternative to medication for managing mood and anxiety. - WHM impacts brain chemistry, function, and individual psychology. - Further research is needed to understand the effects of WHM. ###### [The Effect of Mindset and Breathing Exercises on Physical and Mental Health in Persons with Spinal Cord Injury—A Pilot Feasibility Study (2023)](https://www.mdpi.com/1660-4601/20/18/6784 "Article: The Effect of Mindset and Breathing Exercises on Physical and Mental Health in Persons with Spinal Cord Injury—A Pilot Feasibility Study") **TL;DR** - Feasibility and efficacy of mindset and breathing exercises (WHM) on physical and mental health in persons with SCI - 10 participants followed a 4-week WHM intervention - Adherence to weekly in-person meetings was excellent, no adverse events occurred - Some pre-post differences in physical and mental health outcomes observed - Preliminary evidence supports feasibility and efficacy of WHM in people with SCI - Results warrant a randomized-controlled trial of this intervention in people with SCI **Results** - Feasibility and efficacy of mindset and breathing exercises (WHM) on physical and mental health in persons with SCI - Adherence to weekly in-person meetings was excellent - No adverse events occurred during the intervention period - Some pre-post differences in physical and mental health outcomes observed - Preliminary evidence supporting the feasibility and efficacy of WHM in SCI - Suggests a randomized-controlled trial of this intervention in SCI population **Methods Used** - WHM intervention with mindset and breathing exercises - In-person exit-interview to collect qualitative information on participants' experiences - Tests and questionnaires administered to assess physical and mental health outcomes **Limitations** - Lack of motivation to perform breathing exercises mentioned as a barrier. - Time and effort required for the intervention mentioned as a barrier. - Difficulty in performing exercises alone mentioned as a barrier. - Difficulty in giving up control and expressing emotions mentioned as a barrier. **Practical Implications** - Preliminary support for feasibility and efficacy of WHM in SCI. - Follow-up study needed with randomized-controlled trial and longer intervention. - WHM may improve physical and mental health outcomes in SCI. ###### [Modulation of Pain Sensitivity by a Hyperventilatory Breathing Exercise and Cold Exposure Training (2023)](https://www.dovepress.com/modulation-of-pain-sensitivity-by-a-hyperventilatory-breathing-exercis-peer-reviewed-fulltext-article-JPR "Article: Modulation of Pain Sensitivity by a Hyperventilatory Breathing Exercise and Cold Exposure Training") **TL;DR** - Hyperventilatory breathing exercise decreases pain perception induced by electrical stimulus. - Cold exposure training may decrease pain perception induced by ice water. - Effects on patients with autoimmune diseases are yet to be determined. **Results** - Hyperventilatory breathing exercise decreases pain perception induced by electrical stimulus. - Cold exposure training may decrease pain perception induced by hand immersion in ice water. - Systemic inflammation nullifies the decreased pain perception during ice water test. **Methods Used** - NASQ measurements performed during two studies - Evaluation of NASQ parameters before and after training program - Evaluation of NASQ parameters during experimental endotoxemia **Limitations** - The study was not formally powered for the NASQ endpoints. - Significant changes were found in some groups but not others. - The study only included 40 male participants. - The methods and procedures are described elsewhere. **Practical Implications** - Breathing exercise decreases pain perception induced by electrical stimulus. - Cold exposure training may decrease pain perception induced by ice water. - Effects on patients with autoimmune diseases are yet to be determined. ###### [The positive effects of combined breathing techniques and cold exposure on perceived stress: a randomized trial (2023)](https://link.springer.com/article/10.1007/s12144-022-03739-y "Article: The positive effects of combined breathing techniques and cold exposure on perceived stress: a randomised trial") **TL;DR** - The paper explores the positive effects of combined breathing techniques and cold exposure on perceived stress. - The Wim Hof Method (WHM) combines pranayama-like breathing and cold exposure. - Previous research has focused on physiological measures, but this study highlights the association with reduced perceived stress. - The experiment took place in June 2021 during the COVID-19 pandemic. **Results** - Breathing techniques are associated with decreased levels of perceived stress. - Cold exposure is associated with decreased levels of perceived stress. **Methods Used** - Combination of pranayama-like breathing and cold exposure (WHM) - Exercises to increase practitioners' commitment - Measures for perceived stress (PSS-10 and PSQ) - Dependent variable: perceived stress - Alternative explanations were considered and ruled out **Limitations** - Inclusion criteria were relaxed for participant eligibility. - The experiment was conducted over a two-week period. **Practical Implications** - WHM can be used to reduce perceived stress. - Combined breathing techniques and cold exposure have the largest positive impact. - Exercises considering both forms of hormetic stress are effective for reducing stress. - WHM exercises are simple and applicable for a wide audience. ###### [The Effects of Cold Exposure Training and a Breathing Exercise on the Inflammatory Response in Humans: A Pilot Study (2022)](https://pubmed.ncbi.nlm.nih.gov/35213875/ "Article: The Effects of Cold Exposure Training and a Breathing Exercise on the Inflammatory Response in Humans: A Pilot Study") **TL;DR** - Training program of cold exposure and breathing exercise attenuates inflammatory response. - Breathing exercise plays a pivotal role in the anti-inflammatory effect. - Results need to be replicated before application in clinical populations. **Results** - Combination of cold exposure training and breathing exercise attenuates inflammatory response. - Both breathing exercises increase plasma epinephrine levels. - Cold exposure training alone does not modulate inflammatory response. - Breathing exercise enhances anti-inflammatory and attenuates proinflammatory cytokine levels. - Cold exposure training enhances the immunomodulatory effects of the breathing exercise. **Methods Used** - Participants were randomized to short or extensive training in breathing exercises. - Participants were randomized to cold exposure training, breathing exercise training, or both. - Participants were intravenously challenged with LPS. - Plasma cytokine levels were measured as the primary outcome. **Practical Implications** - Voluntary activation of the sympathetic nervous system can attenuate the inflammatory response. - Cold exposure and breathing exercises can be provided by an independent trainer. - The anti-inflammatory effect of the training intervention is primarily due to the breathing exercise. ###### ["Involvement of lactate and pyruvate in the anti-inflammatory effects exerted by voluntary activation of the sympathetic nervous system." Metabolites (2020).](https://www.mdpi.com/2218-1989/10/4/148/htm "Read more about Article: `Involvement of lactate and pyruvate in the anti-inflammatory effects exerted by voluntary activation of the sympathetic nervous system.` Metabolites 2020.") **TL;DR** - Voluntary activation of the sympathetic nervous system reduces inflammation. - Breathing exercises play a pivotal role in the observed effects. - Increased activity of the Cori cycle is observed in trained individuals. - Elevated levels of lactate and pyruvate correlate with anti-inflammatory effects. - Lactate and pyruvate enhance IL-10 production and attenuate pro-inflammatory cytokines. **Results** - Voluntary activation of the sympathetic nervous system attenuates the systemic inflammatory response. - Breathing exercises acquired during the training program enhance activity of the Cori cycle. - Elevated levels of lactate and pyruvate correlate with increased anti-inflammatory interleukin (IL)-10. - Lactate and pyruvate enhance IL-10 production and attenuate pro-inflammatory cytokine release. **Methods Used** - Training program consisting of cold exposure, breathing exercises, and meditation. - Plasma metabolome analysis of 224 metabolites at six timepoints. - In vitro validation experiments with lactate and pyruvate. **Limitations** - Only male volunteers were included, limiting generalizability. - Uncertainty of the source of measured metabolites. - Lack of samples stored for determination of intracellular metabolites in immune cells. **Practical Implications** - Voluntary activation of the sympathetic nervous system can attenuate systemic inflammation. - Breathing exercises play a pivotal role in the observed effects. - Inclusion of both sexes would yield more inter-individual variation. - Combining plasma metabolomics with intracellular metabolite determination would be more powerful. ###### ["Battling Arthritis" — An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis - A proof of concept trial (2019)](https://www.wimhofmethod.com/blog/battling-arthritis) **TL;DR** - Add-on training program involving breathing exercises, cold exposure, and meditation - Safe and effective in reducing inflammation and disease activity in axial spondyloarthritis - No significant adverse events reported - Further research needed to evaluate clinical efficacy and mechanism of action - Adherence to the training program was high among participants. **Results** - 24 patients were randomized to early or late intervention group - No statistical differences between groups in demographics and baseline characteristics - 2 patients in early intervention group discontinued due to adverse event - 3 patients in control group discontinued after control period - 21 participants started with intervention, 19 completed intervention period - All 11 patients in late intervention group completed control period **Methods Used** - Open-label, randomized, one-way crossover clinical proof-of-concept trial - Intervention group and control group - Breathing exercises, cold exposure, and meditation as the intervention - 8-week intervention period - Safety as the primary endpoint - Secondary endpoints: change in hs-CRP, serum calprotectin levels, and ESR - Exploratory endpoints: disease activity, quality of life, anxiety, and depression **Limitations** - Small sample size (24 patients) - Lack of a placebo group for comparison - Need for further research with larger sample size and clinical efficacy evaluation **Practical Implications** - The add-on training program can safely be applied in patients with axial spondyloarthritis. - The program potentially modulates inflammatory response. - Further research is needed to evaluate clinical efficacy and mechanism of action. ###### The Mind Over Matter Study - ["Brain over body" – A study on the willful regulation of autonomic function during cold exposure (2018)](https://www.wimhofmethod.com/blog/study-brain-over-body "Read more about Article: “Brain over body”–A study on the willful regulation of autonomic function during cold exposure") **TL;DR** - Study on Wim Hof, the "Iceman", and his ability to withstand extreme cold exposure - WHM activates brain areas for pain/cold modulation and self-reflection - Hyperventilation primes autonomic system and releases stress hormones - Release of endogenous opioids/cannabinoids leads to euphoria and well-being - WHM allows practitioners to develop control over autonomous system components **Results** - Skin temperature data showed differences between the Iceman and typical controls. - Significant fMRI differences in activation in the brainstem and insula regions. - PET results showed comparable responses in the Iceman's body compared to typical controls. **Methods Used** - PET/CT imaging with tracers HED and FDG - fMRI paradigm with periods of mild hypothermia - Whole-body garment with small-diameter plastic tubing for cold exposure - Combination of forced breathing, cold exposure, and meditation (WHM) technique **Limitations** - CNS effects related to skin temperature changes, not body temperature. - Potential differences in temperature perception and physiological responses. - Effects of pCO2 changes and hypocapnia on neuronal activity. - Temporal and spatial limitations of fMRI in brainstem nuclei. - Unclear anatomical location of observed significant activations in the pons region. **Practical Implications** - The technique used in the study allows practitioners to withstand severe cold exposure. - Activation of brain areas during the technique promotes stress-induced analgesia. - The technique may increase control over the brain's autonomous system. ###### [The Role of Outcome Expectancies for a Training Program Consisting of Meditation, Breathing Exercises, and Cold Exposure on the Response to Endotoxin Administration: a Proof-of-Principle Study (2015)](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819555/pdf/10067_2015_Article_3009.pdf "Read more about Article: The Role of Outcome Expectancies for a Training Program Consisting of Meditation, Breathing Exercises, and Cold Exposure on the Response to Endotoxin Administration: a Proof-of-Principle Study") **TL;DR** * Study on the effects of a training program on immune response - Optimism associated with higher plasma epinephrine and IL-10 levels - Positive expectations of training associated with lower flu-like symptoms - Trained group showed fewer symptoms and increased anti-inflammatory response to endotoxin administration **Results** - Generalized outcome expectancy optimism is associated with higher plasma epinephrine and IL-10 levels. - Neuroticism is not significantly associated with the response to endotoxin administration. - Positive expectation of training effects is associated with lower flu-like symptom report. **Methods Used** - Participants practiced breathing techniques before endotoxin administration. - Clinical symptom report was measured using a Likert scale. - Generalized outcome expectancy optimism was assessed as a potential determinant. **Practical Implications** - Training program could be used to change immune-modulating responses. - Optimism-inducing interventions may potentiate the effects of training. - Potential implications for the treatment of autoimmune diseases. ###### The Radboud Study - [Voluntary Activation of The Sympathetic Nervous System and Attenuation of the Innate Immune Response In Humans (2014)](https://media-cdn.wimhofmethod.com/uploads/kcfinder/files/PNAS.pdf) **TL;DR** - Voluntary techniques can stimulate sympathetic input to the adrenal medulla. - Techniques can influence the sympathetic nervous system and immune system. - Training can lead to higher leukocyte counts and lymphocyte increase. - Techniques may have implications for treating conditions associated with inflammation. **Results** - Trained individuals practicing breathing techniques showed immediate decrease in pCO2 and bicarbonate levels. - Trained individuals had an increase in pH, indicating acute respiratory alkalosis. - Oxygen saturation levels dropped to around 50 in trained individuals during hyperhypoventilation. - Heart rate increased and normalized earlier in trained individuals compared to control group. - Trained individuals had less pronounced fever and normalized temperature earlier. - Trained individuals had attenuated self-reported symptoms compared to control group. - Techniques stimulate sympathetic input to adrenal medulla, resulting in increased epinephrine levels. - Techniques can be used to influence sympathetic nervous system and immune system voluntarily. - Implications for treatment of conditions associated with excessive inflammation, especially auto-immune diseases. **Methods Used** - Randomized controlled study with 30 healthy male volunteers - Training program including meditation, cold exposure, breathing techniques, and strength exercises - Experimental endotoxemia using lipopolysaccharide (LPS) administration - Monitoring of symptoms, temperature, hemodynamic response, and cytokine response - Analysis of blood gas parameters and catecholamine levels - Statistical analysis using Graphpad Prism software **Practical Implications** - Techniques can influence sympathetic nervous system and immune system voluntarily. - Can be used to treat conditions associated with excessive inflammation. - Potential implications for the treatment of auto-immune diseases. ###### [Frequent Extreme Cold Exposure and Brown Fat and Cold-Induced Thermogenesis: A Study in a Monozygotic Twin (2014)](https://media-cdn.wimhofmethod.com/uploads/kcfinder/files/WHM_BrownFat.PDF "Read more about Article: Frequent Extreme Cold Exposure and Brown Fat and Cold-Induced Thermogenesis: A Study in a Monozygotic Twin") **TL;DR** - Study compared the effects of extreme cold exposure on BAT and CIT in a man and his twin brother. - Both subjects had comparable BAT activity and high CIT. - The g-Tummo breathing technique may contribute to increased heat production. - Results suggest that extreme cold exposure does not affect BAT activity. - Genetic factors and lifestyle both influence BAT activity and heat generation. **Results** - BAT activity was comparable between the Iceman and his twin brother. - Both subjects had high cold-induced thermogenesis (CIT). - The g-Tummo breathing technique may contribute to increased heat production. - The results suggest that frequent exposure to extreme cold does not affect BAT activity and CIT. **Methods Used** - Measurements included BAT activity and respiratory muscle activity through imaging. - Energy expenditure was measured through indirect calorimetry. - Body temperatures, cardiovascular parameters, skin perfusion, and thermal sensation were measured. - Polymorphisms for uncoupling protein-1 and b3-adrenergic receptor were determined. **Limitations** - Low subject number - Both participants practiced the g-Tummo like breathing technique ###### [Controlled Hyperventilation After Training May Accelerate Altitude Acclimatization (2014)](https://media-cdn.wimhofmethod.com/uploads/kcfinder/files/Kilimanjaro.pdf "Read more about Article: Controlled Hyperventilation After Training May Accelerate Altitude Acclimatization") **TL;DR** - The Wim Hof method can improve physical potential and health control. - Controlled hyperventilation and cold exposure can stimulate endurance and energy levels. - The method has a biological effect on the autonomic nervous system. - None of the trekkers experienced severe AMS despite symptoms. - Rapid ascent with little acclimatization may be relevant for AMS prevention. - Further research is needed to understand the physiology and treatment of these conditions. **Results** - All 26 trekkers had symptoms of AMS to some extent. - None of the trekkers had severe AMS. - The method used may safely accelerate acclimatization and relieve AMS symptoms. - Further research is needed to understand the physiology and treatment of these conditions. **Methods Used** - Intense mindset coaching - Controlled hyperventilation - Breathing techniques for gradual cold exposure **Limitations** - Rapid ascent is discouraged due to potentially lethal risks. **Practical Implications** - The Wim Hof method may safely accelerate acclimatization and relieve AMS symptoms. - Rapid ascent with little time for acclimatization may be possible. ###### [The Influence of Concentration/meditation on Autonomic Nervous System Activity and the Innate Immune Response: A Case Study (2012)](https://media-cdn.wimhofmethod.com/uploads/kcfinder/files/WHM_Hopman.pdf "Read more about Article: The Influence of Concentration/meditation on Autonomic Nervous System Activity and the Innate Immune Response: A Case Study") **TL;DR** * Individual's concentration/meditation technique attenuates innate immune response. - Technique results in controlled stress response and sympathetic nervous system activation. - Increased levels of catecholamines and cortisol during concentration/meditation. - In vivo cytokine response and clinical symptoms remarkably low compared to others. - Further investigations needed to reproduce results in larger groups. **Results** - Concentration/meditation technique attenuates the innate immune response. - Controlled stress response characterized by sympathetic nervous system activation and catecholamine/cortisol release. - Increased circulating concentrations of catecholamines and plasma cortisol during endotoxemia. - In vivo cytokine response and clinical symptoms were remarkably low compared to previous participants. **Methods Used** - Ex vivo cytokine response measured before and after ice immersion. - In vivo innate immune response studied during human endotoxemia. - Comparison of results with a historical cohort of 112 individuals. **Limitations** - Study is based on a single individual, limiting cause-effect relationship. - Absence of an additional endotoxemia experiment without concentration/meditation technique. - Participant is older than the comparison group, age difference considered. **Practical Implications** - Concentration/meditation technique may result in a controlled stress response. - Attenuation of the innate immune response through sympathetic nervous system activation. - Further investigations needed to reproduce results in larger groups of individuals. --- **TL;DR** ... **Results** ... **Methods Used** ... **Limitations** ... **Practical Implications** ...