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Writer's pictureThomas P Seager, PhD

Hormesis for Health

Updated: Dec 1

Is comfort causing hypertension?

upside down "U" dose-response curve

Summary

  • "Hormesis" is the process by which the body benefits from temporary stress. For example, exercise can make your muscles sore and feel weak, but it is also how you stimulate muscle growth to become stronger.

  • Cold stress is hormetic in the sense that it stimulates changes in the body that improve health. For example, cold plunge causes high blood pressure in the short term, and reduces blood pressure longer term.

  • "Intermittent living" describes the process by which varying stress and recovery leads to improved health outcomes.


How comfort can kill you

The medical term for a stress dose that can stimulate a beneficial response in a patient is called hormesis (Kendig et al. 2010).

Hormesis is a fundamental concept in evolutionary theory. From the beginning through the present time, life on earth has existed in harsh environments in which cells are often exposed to free radicals and toxic substances. To avoid extinction organisms have developed complex mechanisms to cope with the environmental hazards. - Mattson (2008)

The concept of hormesis originally emerged in toxicology to describe the potential benefits of small doses of what would be poisonous in larger quantities. For example, too little selenium results in detrimental health effects due to insufficiency. Just the right amount of selenium supports health, but too much is toxic. Now it is widely recognized that stress universally stimulates adaptive responses in the body that are necessary for good health. In fact, Hans Seyle MD, PhD, who first introduce the modern concept of "stress" in 1956, famously wrote "the complete absence of stress is death" (Selye 1973).

Adaptive responses to low doses of a stressor that is toxic at high doses have been observed in essentially all organisms studied so far, including prokaryotes, fungi, plants, invertebrates and mammals, including humans. - Calabrese et al. (2007)

Since originally postulated as critical to health, hormesis has been known by different names, including preconditioning, inoculation, and exposure therapy.


Exercise, food, and sun exposure all exhibit hormetic effects. Too little results in weakness, but too much can be fatal. Add a little bit of each, and health improves, but too much results in harm again. Optimum health is found in the midsection of the dose-response curve -- not too little, not too much.

While hormesis is most often thought of in the context of exposures to exogenous agents or environmental conditions, it should also be recognized that hormesis is integral to the normal physiological function of cells and organisms. - Mattson (2008).

Hormetic effects have been discovered in some surprising exposures, including ionizing radiation (Kabilan et al. 2020). For example, in my toxicology in graduate school, I was taught that there is no safe dose of radiation -- i.e., that any dose of radiation would increase mortality.


It turns out that's not true. In fact, radiation that can be deadly in high doses can be beneficial at low doses -- and this principle applies to many different types of stressors.


Deliberate cold exposure is one of those surprising hormetic stressors. Too little cold stress results in a loss of brown fat and leaves the body vulnerable to metabolic and thyroid dysfunction. Just the right amount of cold supports general health, well-being, and a long life. However, too much cold all at once can be dangerous, especially for people with untreated hypertension (high blood pressure).


Hormesis for Hypertension

I'm in touch with an older customer who stands out in his social circle for his ice bathing practice. His friends are apparently dubious. Nevertheless, he's been consistent in his pursuit of cold plunge therapy, so he reports that his friends ask him a lot of questions about it.


Today, he passed this question on to me:


What’s the effect on high blood pressure from the ice bath?


For many older Americans, hypertension (chronically elevated high blood pressure) is a serious concern. The CDC estimates that over 60% of the US population over 60 years old either take medication for high blood pressure, experience systolic blood pressure greater than or equal to 140 mmHg, or have diastolic blood pressure greater than or equal to 90 mmHg.


Because elevated high blood pressure can be associated with shorter life expectancy, it may be that our customer's friends are asking about the effects of the ice bath out of a legitimate concern for his medical safety.


A number of scientific studies reinforce their concerns. For example, Hintsala et al. (2013) from the University of Oulu in Finland measured the blood pressure response in 41 hypertensive men aged 55-65 years during 15 minutes of whole-body cold air exposure (−10°C, wind 3 m/s, winter clothes), compared to 20 men without hypertension.


They discovered that short-term deliberate cold exposure will elevate systolic blood pressure by 20 mm Hg or more. The Finnish researchers concluded, "Short-term cold exposure increases central aortic blood pressure and cardiac workload, and myocardial oxygen demand slightly increases in relation to blood supply in untreated hypertensive middle-aged men. Because of the higher baseline blood pressure among hypertensive subjects, the cold-induced rise in central aortic blood pressure may increase the risk of adverse cardiovascular health effects."


Moreover, other studies have found similar results, even at more mild temperatures (e.g., +10°C, Korhonen 2006). As I explained in 'Are you getting enough vasoconstriction?', cold exposure causes contraction of the smooth muscle tissues that control blood flow to the extremities, thereby conserving body heat for the internal organs. The reduced blood flow to the limbs results in increased pressure in the torso. It makes sense that short-term cold exposure results in short-term increases in blood pressure, and the risk to those with hypertension suggests that they consult with a medical professional who knows them well prior to undertaking a practice of ice baths.


However, what can be bad for the body in the short term can be good for the body in the long term. For example, cold plunge therapy stimulates mitobiogenesis -- i.e., the formation of new mitochondria. As I wrote in Ice Baths for Better Sex, it is the mitochondria in the endothelial cells that lines the blood vessels that produce the ATP necessary to produce nitric oxide (NO) and dilate blood vessels. Improved mitochondrial function can lead to better blood flow and ultimately reduced blood pressure. According to Deborah Taylor at Outlive Labs in Florida, in one client the positive effect of cold plunge was so profound that they were able to discontinue their blood pressure medication altogether.


Benefits of brown fat

Over the longer term, the metabolic and circulatory benefits of the ice bath may outweigh the shorter-term risks of increased blood pressure. For example, Becher et al. (2020) compared over 5000 matched pairs of patients belonging to one of two groups -- those with brown fat and those without. They discovered that the brown fat positive group enjoyed several health advantages over those without, including:


  • lower prevalence of type II diabetes,

  • a healthier balance of cholesterol levels,

  • lower incidence of coronary artery disease & congestive heart failure, and

  • reduced likelihood of hypertension.


They wrote:

Our study illustrates that individuals with thermogenic fat have significantly improved metabolic profiles. This effect is not only limited to diabetes, but extends to coronary artery disease, congestive heart failure and hypertension. Furthermore, the effects of brown fat on metabolic and cardiovascular disease are most pronounced among individuals with elevated body mass index. Those obese individuals who retain brown fat activity appear to be protected against conditions linked to excess weight. This notion further supports the potential of brown fat as a therapeutic target beyond weight loss itself, but as a means to uncouple obesity from disease. - Becher et al. (2020)

Deliberate cold exposure recruits brown fat

The Becher et al. findings confirm two things that we already knew:


  1. Cold exposure activates and recruits brown fat. Because the researchers reviewed thousands of PET scans made available by the Memorial Sloan Kettering Cancer Center in New York City, they were able to compile a robust dataset comparing the prevalence of brown fat to the average monthly temperature on the date of the scan. Unsurprisingly, brown fat increased during colder months, confirming findings in smaller cohorts that show brown fat activation in Danish winter swimmers (e.g., Søberg et al. 2021).

  2. Americans generally lose brown fat as they age. Although it has long been understood that human babies are born with ample stores of brown fat to facilitate thermoregulation under extreme weather conditions, until 2009, brown fat could not be detected in adults, and most medical professionals believed it was completely lost in maturity. Only after advancements in PET technology allowed imaging of brown fat did definitive evidence emerge that, despite the tendency for brown fat to decline with age, it could be retained into adulthood and correlated with regular cold exposure. This new study compiles the largest data set ever, showing that the percentage of adults with detectable brown fat declines with age, from almost 60% at age 20 years to as little as zero after age 90. (The study does not answer whether the decline is a cause of aging or an effect).



Hormesis looks like a contradiction

These two contrasting findings -- that deliberate cold exposure can cause high blood pressure in the short term but be associated with lower blood pressure in the longer term -- might seem counter-intuitive except for the fact that the principle of hormesis suggests brief periods of stress followed by contrasting periods of recovery can be good for our health. Nonetheless, an emerging movement in medicine emphasizes a restoration of the naturalistic rhythms and variations that have been removed from modern industrial life. To avoid the constancy of an injurious, machine-like existence, we must re-introduce to our lives the kind of irregular stressors that our ancestors could not avoid.


Intermittent Living

While the concept of hormesis is finally reaching the medical mainstream (e.g., Calabrese 2018), two Dutch scientists coined a new term for adopting a hormetic approach to health called "intermittent living" (Pruimboom & Muskiet 2018). They describe four examples: thirst, hunger, temperature, and oxygen.


  1. Intermittent thirst is the practice of deliberately allowing yourself to feel "mild thirst," which they claim will reduce cortisol levels and "decrease anxiety, fear, and aggressive behavior."

  2. Intermittent hunger (fasting) is the practice of skipping meals to initiate autophagy of weak or damaged cells, promote mitochondrial health, and increase insulin sensitivity.

  3. Intermittent hot and cold exposure is the practice of incorporating sauna and ice baths to stabilize metabolism, reduce blood glucose levels, guard against obesity, and promote mitochondrial proliferation.

  4. Intermittent hypoxia/hypercapnia is the practice of modulating blood oxygen and carbon dioxide levels to reduce inflammation, boost immune system function, slow aging, and ameliorate feelings of panic or anxiety.


The mechanisms by which intermittent practices operate are similar to the way exercising our muscles can make them weak and sore at first, then prompt our body to recover during rest and soon become stronger. Thus, rest and recovery are as important to building strong muscles as exercise.

The upside-down 'U' shape of the typical hormetic dose-response curve resolves the paradox of the ice bath and hypertension. That is, the intermittent living hypothesis suggests that a little bit of what looks bad for you in the short term might actually be good for you in the longer term -- as long as it doesn't kill you first.


I can't give you medical advice nor tell you whether cold plunge therapy is a good choice for you because I'm not your doctor, and I don't know where your dose-response optimum resides. Medical studies draw inferences and make generalities from a large ensemble of data, but none of the subjects in the study are you. That is, what is statistically true for the people in the study may not hold true for you. When it comes to an ice bath practice, there is no study that can substitute for your own experience and monitoring of your own response.


What I can do is tell you more about what's been working for me:



Note: Hypertension is a contraindication to cold

Hypertension can be a serious disorder that escapes notice until it is too late. Screening for high blood pressure is inexpensive and may motivate lifestyle changes or other interventions that prolong life and health span. The principle of hormesis suggests that extending health span requires discomfort or inconvenience in the short term in the pursuit of longer-term health goals. Nonetheless, an acute hypertensive episode accompanied by back or chest pain, shortness of breath, or visual disturbances may be a medical emergency.


References

  • Becher T, Palanisamy S, Kramer DJ, Marx SJ, Wibmer AG, Del Gaudio I, Butler SD, Jiang CS, Vaughan R, Schöder H, Di Lorenzo A. Brown Adipose Tissue is associated with improved cardiometabolic health and regulates blood pressure. BioRxiv. 2020 Feb 10:2020-02.

  • Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, Cedergreen N, Cherian MG, Chiueh CC, Clarkson TW, Cook RR. Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose–response framework. Toxicology and applied pharmacology. 2007 Jul 1;222(1):122-8.

  • Hintsala H, Kandelberg A, Herzig KH, Rintamäki H, Mäntysaari M, Rantala A, Antikainen R, Keinänen-Kiukaanniemi S, Jaakkola JJ, Ikäheimo TM. Central aortic blood pressure of hypertensive men during short-term cold exposure. American journal of hypertension. 2014 May 1;27(5):656-64.

  • Kabilan U, Graber TE, Alain T, Klokov D. Ionizing radiation and translation control: A link to radiation hormesis?. International Journal of Molecular Sciences. 2020 Sep 11;21(18):6650.

  • Kendig EL, Le HH, Belcher SM. Defining hormesis: evaluation of a complex concentration response phenomenon. International journal of toxicology. 2010 May;29(3):235-46.

  • Korhonen I. Blood pressure and heart rate responses in men exposed to arm and leg cold pressor tests and whole-body cold exposure. International journal of circumpolar health. 2006 Apr 18;65(2):178-84.

  • Mattson MP. Hormesis defined. Ageing research reviews. 2008 Jan 1;7(1):1-7.

  • Pruimboom L, Muskiet FA. Intermittent living; the use of ancient challenges as a vaccine against the deleterious effects of modern life–A hypothesis. Medical Hypotheses. 2018 Nov 1;120:28-42.

  • Selye H. The Evolution of the Stress Concept: The originator of the concept traces its development from the discovery in 1936 of the alarm reaction to modern therapeutic applications of syntoxic and catatoxic hormones. American scientist. 1973 Nov 1;61(6):692-9.

  • Søberg S, Löfgren J, Philipsen FE, Jensen M, Hansen AE, Ahrens E, Nystrup KB, Nielsen RD, Sølling C, Wedell-Neergaard AS, Berntsen M. Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men. Cell Reports Medicine. 2021 Oct 19;2(10).


 

About the Author

Thomas P. Seager, PhD, is an Associate Professor in the School of Sustainable Engineering at Arizona State University. Seager co-founded the Morozko Forge ice bath company and is an expert in using ice baths to build metabolic and psychological resilience.







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