#21 How Cryotherapy Affects the Brain, the Immune System, Metabolism, and Athletic Performance
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Cryotherapy – a hormetic stressor
If you’ve ever popped outside on a cold winter’s day without your coat, you know that your body reacts quickly: You start to shiver, and your fingers, hands, and toes turn blue. Stay out a little longer, and your thinking might become a little muddled. Cold stresses the body. So why would anyone intentionally want to be exposed to extreme cold? Enter cryotherapy – the practice of exposing the body (or specific areas of the body) to extremely cold temperatures for defined time periods. Much like exercise, extreme heat (such as from sauna use), and fasting, cryotherapy stresses the body in a hormetic manner, triggering cellular responses in the body that exceed what is actually needed to compensate for the otherwise damaging insult.
Cryotherapy on the brain
Exposure to cold has profound effects on many parts and functions of the body, including the brain, immune system, and metabolism, among others. Perhaps the most clear-cut examples of cryotherapy’s beneficial effects are observed in the brain, where levels of the hormone and neurotransmitter norepinephrine – responsible for vigilance, attention, focus, and positive mood – increase markedly when the body is exposed to extreme cold.
Cryotherapy also switches on the activity of cold shock proteins, especially RNA binding motif 3, or RBM3, which is found in many of the body’s tissues, including the brain. RBM3 increases protein synthesis at the ends of dendrites – where synapses form – and protects the brain from cognitive and behavioral deficits associated with some neurodegenerative diseases.
Cryotherapy on inflammation and immune function
At the core of many chronic diseases and the aging process is one common feature: inflammation. Cryotherapy, however, appears to reduce inflammation. One way it does this is via its influence on norepinephrine, which decreases levels of tumor necrosis alpha, a proinflammatory cytokine instrumental in promoting systemic inflammation. Norepinephrine inhibits other proinflammatory processes and may reduce the pain and inflammation associated with arthritis, among other conditions.
Another critical factor in chronic disease is immune function. Cryotherapy promotes the development of a healthy immune cell population, including cytotoxic T lymphocytes, which play key roles in protecting the body from cancer.
Cryotherapy and metabolism
The metabolic responses to cryotherapy serve one purpose: to warm the body through a process known as thermogenesis. The shivering associated with exposure to cold is well-known: Your muscles start to contract in an involuntary effort to produce heat, a process called shivering thermogenesis. But the body also engages in a more efficient attempt to produce heat, called non-shivering thermogenesis, in which norepinephrine (again) acts on key proteins to uncouple the normal electrical processes within mitochondria. The body responds by producing more mitochondria, effectively converting the body’s white adipose tissue into its more metabolically active counterpart, brown adipose tissue. The greater the amount of brown adipose tissue the body has, the greater the amount of fat it will burn, potentially promoting weight loss.
Cryotherapy and athletic performance
Cold exposure improves athletic performance and recovery, but the benefits come with two caveats: the timing of the cold stressor and the type of the exercise performed.
Shortly after exercise the body initiates a cascade of pro-inflammatory responses. The body eventually counters with an anti-inflammatory response. These complementary, yet opposing forces are necessary for mitochondrial biogenesis and muscle repair and growth. Appropriate timing of cryotherapy, whether local (e.g., ice pack usage) or systemic (e.g., cold water immersion), is critical for optimal benefits. If the cryotherapy is administered too soon after exercise, the delicate balance of responses can be interrupted. The type of exercise matters, too, with greater benefits likely observed with endurance training versus strength training.
Modality matters
In choosing a cryotherapy modality – whole-body cryotherapy, cold-water immersion, or ice packs – a few factors should be considered, such as thermal conductivity, body surface area exposure, and temperature gradient. Whereas each modality has its pros and cons, the data are equivocal for whole-body and cold-water immersion, as long as the exposure is sufficiently long.
Bottom line
A growing body of evidence supports the use of cryotherapy for optimal health and human performance. The jury is still out on exactly how, when, and under what circumstances cryotherapy works best. This podcast takes an in-depth look at the scientific evidence surrounding the practice of cryotherapy.
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Rhonda explains her motivation for producing a podcast about cryotherapy, or cold exposure, and describes the challenges inherent in any discussion about the topic.
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Much of the information in this podcast is also presented in a report written by Rhonda. Report
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How hormetic stressors such as exercise, fasting, and heat or cold exposure are beneficial to the human body.
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A brief overview of what is discussed in this podcast.
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Benefits commonly associated with cold exposure include positive effect on metabolism, athletic performance, muscle soreness, and recovery.
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Anecdotal and empirical evidence suggest that cold exposure improves mood and may be useful in treating depression. Study
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One of the most consistent and profound responses to cold exposure is a robust release of norepinephrine into the bloodstream and brain. Study
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Norepinephrine depletion causes depression. Study
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Norepinephrine plays a key role in the body’s response to cold by increasing vasoconstriction, which reduces heat loss.
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There appears to be a temperature threshold for activating the release of norepinephrine. Study
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Short-term exposure to cold – as little as 20 seconds to 2 minutes – is enough duration to release norepinephrine. Study
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Heat and lactate also trigger norepinephrine release. Learn more about lactate in Rhonda’s podcast with Dr. George Brooks. Episode
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Norepinephrine has profound effects on pain, metabolism, and inflammation – the latter of which is associated with mood due to its influence on serotonin release. Study
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Studies of hibernating animals have shown that exposure to cold triggers the activity of cold shock proteins, specifically RBM3, which is found in many human tissues. Study
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When mice were cooled pharmacologically, they lost synapses, but when re-warmed, RBM3 stimulated regeneration of nearly all the lost synapses. Study
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RBM3 increases protein at the dendrites, where synapses form.
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When mice underwent pharmacological cooling once, the expression of RBM3 increased markedly and lasted for 3 days, but a second exposure to cold had longer, more enduring effects. Study
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Mice with neurodegenerative disease from prion infection experienced delayed neuronal loss and cognitive and behavioral deficits associated with the disease. Study
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The loss of synapses occurs with normal brain aging and is accelerated in neurodegenerative diseases and brain injury.
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Reducing core body temperature by a mere 2°F is enough to induce cold shock proteins, including RBM3, in human astrocytes (a type of brain cell). This effect may be enhanced by melatonin. Study
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Submerging young men in cold water for just one hour reduced core body temperatures. [Study]
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Inflammation plays a key role in disease and the aging process. Study
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Whole-body cryotherapy reduces pain and inflammation associated with arthritis. Study
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Proinflammatory molecules cross the blood-brain barrier and activate the brain’s immune cells.
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Inflammatory molecules may contribute to depression and anxiety by inhibiting release of serotonin. Study
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Having a large number of healthy, inactive immune cells is associated with longevity. Study
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Both anecdotal and epidemiological evidence suggest that winter swimmers have fewer upper respiratory infections. Study
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The body responds to cold by increasing metabolism in an effort to produce heat, a process called thermogenesis.
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There are two types of thermogenesis – shivering and non-shivering.
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Non-shivering thermogenesis is regulated partly by norepinephrine, which increases the expression of uncoupling protein-1 (UCP1) in mitochondria, altering the electrochemical gradient within cells.
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UCP1 ramps up mitochondria production in white adipose tissue, converting it to the more metabolically active brown adipose tissue.
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Cold exposure increases brown adipose tissue in humans and increases the capacity for non-shivering thermogenesis. Study
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Cold-water immersion in a small sample of men increased metabolic rate by as much as 350%. Study
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Experimentally blocking the action of norepinephrine on beta-adrenergic receptors prevents the production of brown adipose tissue. Study
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When mice consumed fish oil, their metabolism increased and body fat decreased, likely due to a brown adipose tissue-mediated mechanism. Study
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Cold exposure may improve athletic performance and recovery, depending on the timing and type of exercise performed.
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Immediately after exercise, the production of proinflammatory cytokines increases, aiding in muscle repair and activating genetic pathways involved in mitochondrial biogenesis.
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Macrophages that are activated in response to exercise-induced inflammation produce IGF-1, an anabolic hormone. Study
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After exercising, the body launches an anti-inflammatory response to the exercise-induced inflammation. This response peaks about one hour after exercising. Study
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The type of exercise performed influences the outcome of cryotherapy or cold-water immersion.
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Depending on the nature of the exercise and the time of the cold exposure, there may be very different and somewhat opposing outcomes. Study
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Whole body cryotherapy done one hour after plyometric exercise showed improvements in a variety of performance measures up to 72 hours after the treatment and reduced pain measures during the next workout. Study
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Cold-water immersion blunted strength-training benefits in men doing leg presses and squats. Study
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In most of the studies involving strength training and cold exposure, the cold was applied immediately after training.
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The first hour after exercise is an important anabolic window and may influence the effectiveness of cold exposure. Study
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The effects of cold exposure on endurance exercise performance are generally positive, primarily due to increases in mitochondrial biogenesis.
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Cold exposure activates PGC-1 alpha, which stimulates mitochondrial biogenesis.
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A single 15-minute exposure to cold water following high intensity running increased PGC-1 alpha in muscle tissue. Study
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Regular exposure to cold water after running increased mitochondrial biogenesis in muscle tissue. Study
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A brief description of how different muscle fiber types work.
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PGC-1 alpha induces a switch to oxidative fatigue-resistant muscle fibers.
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Depletion of PGC-1 alpha in the muscle tissue of mice promotes a shift in muscle fiber composition from slow twitch to fast twitch. Study
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The muscles of mice engineered to have higher than normal levels of PGC-1 alpha are more like type I muscle fibers and have greater resistance to fatigue. Study
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PGC-1 alpha also increases type II-a muscle fibers. Study
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An overview of the effects of whole-body cryotherapy and cold-water immersion on performance.
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Elite runners who engaged in whole-body cryotherapy post exercise had a 20% increase in speed and power up to two days later, likely due to a decrease in inflammation and an increase in anti-inflammatory factors. Study
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Elite runners who engaged in whole-body cryotherapy experienced enhanced muscle recovery due to decreased pro-inflammatory factors and increased anti-inflammatory factors. Study
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Tennis players who engaged in whole-body cryotherapy experienced a decrease in TNF-alpha, an increase in IL-6, and a 4% increase in stroke effectiveness. Study
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Elite cyclists who engaged in cold-water immersion saw performance improvements that were sustained over the training program. Study
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Black bears do not lose muscle protein while hibernating. Study
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Squirrels experience increases in RBM3 in the brain and cardiac and skeletal muscle while hibernating. Study
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PGC-1 alpha protects mice against age-related muscle loss (sarcopenia) and metabolic disease. Study. This study has been retracted.
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Heat shock proteins can be induced by cold exposure. Study
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Learn more about the benefits of sauna use and its effects on heat shock proteins in this podcast. Episode
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A brief overview of the factors that differentiate cold exposure modalities.
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Multiple studies comparing norepinephrine response after cold-water immersion versus whole-body cryotherapy have found that the two modalities are more or less identical. Study
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A thousand-mile-up summary of cryotherapy’s benefits.
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A word of caution before practicing any form of cryotherapy.
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