#021 How Cryotherapy Affects the Brain, the Immune System, Metabolism, and Athletic Performance
Dr. Rhonda Patrick explains how cold exposure, through cryotherapy and cold water immersion, acts as a hormetic stressor. It explores its benefits on brain health, mood, immune function, metabolism, and athletic performance, while also discussing crucial timing considerations for post-exercise recovery.
Deep Dive Analysis
14 Topic Outline
Introduction to Cold Exposure as Hormetic Eustress
Cold Exposure's Effects on Brain, Mood, and Focus
Cold Shock Proteins and Synaptic Regeneration in the Brain
Human Relevance of Cold Shock Proteins and Core Body Temperature
Cold Exposure's Impact on Inflammation and Immune Function
Cold Exposure, Weight Loss, and Thermogenesis
Brown Adipose Tissue and Non-Shivering Thermogenesis
Cold Exposure Increasing Antioxidant Enzyme Activity
Cold Shock, Muscle Mass, Performance, and Recovery Timing
Impact of Cold Exposure on Strength Training
Impact of Cold Exposure on Endurance Activities and Mitochondrial Biogenesis
Cold Exposure and Muscle Atrophy Prevention
Comparing Whole-Body Cryotherapy and Cold Water Immersion
Summary of Key Takeaways and Cautionary Notes
8 Key Concepts
Hormesis
Hormesis describes a type of stress that, in the right doses, serves as a short-term stressor triggering cellular responses in the body that exceed what is actually needed to compensate for otherwise damaging insults, leading to a net gain in resilience.
Norepinephrine
Norepinephrine is both a hormone and a neurotransmitter robustly released during cold exposure, involved in vigilance, focus, attention, and mood. It also acutely increases vasoconstriction and plays a role in reducing inflammation by decreasing TNF-alpha.
Cold Shock Proteins (RBM3)
Cold shock proteins are a class of proteins specific to cold exposure, with RNA binding motif 3 (RBM3) being particularly important. RBM3 is found in the brain and other tissues, and its activity is crucial for the regeneration of synapses that break down during cold exposure, potentially protecting against neurodegeneration.
Shivering Thermogenesis
This is a type of cold-induced thermogenesis that occurs in muscle tissue, involving ramping up metabolism and muscle contractions to produce heat. It works because metabolism is not 100% efficient and produces heat as a byproduct.
Non-shivering Thermogenesis
This type of cold-induced thermogenesis occurs in adipose tissue (fat) and does not involve shivering. It is primarily responsible for the fat-burning effect of cold exposure, often happening after the body has adapted to cold.
Uncoupling Protein 1 (UCP1)
UCP1 is a protein whose expression is increased by cold-induced norepinephrine. It uncouples mitochondria, meaning it disrupts the electrochemical gradient, causing mitochondria to frantically transport electrons from stored fat (fat oxidation) to re-establish the gradient, producing heat as a byproduct.
Brown Adipose Tissue (BAT)
BAT is a special type of metabolically active fat tissue that contains more mitochondria per cell, giving it a brown color. It plays a key role in non-shivering thermogenesis, burning fat to produce heat, and its presence is inversely correlated with body fat percentage in adults.
Mitochondrial Biogenesis
This is the process of creating more mitochondria, which are the powerhouses of the cell. Cold exposure activates the PGC1-alpha gene, which is the master regulator of mitochondrial biogenesis, leading to an increased number of mitochondria in muscle cells and enhanced aerobic capacity.
7 Questions Answered
Bad stress, or distress, results from things like inadequate sleep or emotional rumination. Good stress, or eustress, includes activities like exercise, intermittent fasting, heat stress, and cold stress, which are hormetic and trigger beneficial cellular responses.
Cold exposure induces a robust release of norepinephrine, a neurotransmitter and hormone involved in vigilance, focus, attention, and mood. Decreased norepinephrine is associated with inattention, decreased focus, low energy, and poor mood, suggesting cold-induced increases can improve these states.
Research in mice shows that cold exposure can increase the cold shock protein RBM3, which is necessary for regenerating synapses that are lost due to cold or neurodegenerative insults. This suggests a potential for protecting against synapse loss in conditions like Alzheimer's and Parkinson's disease.
Cold-induced norepinephrine inhibits inflammatory pathways by decreasing potent inflammatory molecules like TNF-alpha and macrophage inflammatory protein 1 alpha. This reduction in systemic inflammation can be beneficial for conditions like arthritis and may also reduce brain inflammation.
Yes, cold exposure increases metabolism through cold thermogenesis, which burns fat to produce heat. It also increases brown adipose tissue (BAT) and non-shivering thermogenesis, where BAT actively burns fat, contributing to weight loss.
For strength training, cold water immersion *immediately* after exercise may blunt long-term muscle hypertrophy and strength gains by interfering with beneficial inflammatory processes. However, for endurance activities, cold exposure can boost mitochondrial biogenesis and improve performance and recovery, especially if timed later after exercise.
They are probably not the same, though both induce a robust norepinephrine release. Differences lie in thermal conductivity (ice > water > air), surface area exposed (whole body in cryotherapy vs. often partial in CWI), and temperature gradient (cryotherapy air is much colder). People can also stay in cold water for longer durations than cryotherapy chambers.
25 Actionable Insights
1. Consult Physician Before Cold Exposure
Always consult a physician before starting any new cold exposure activity like cold water immersion, winter swimming, or cryotherapy. This is especially important if you have coronary or other heart-related risk factors, or before attempting contrast therapy (rapid hot to cold transitions).
2. Embrace Hormetic Stressors
Incorporate activities like exercise, intermittent fasting, heat stress (sauna), and cold stress (cold water immersion/cryotherapy) into your routine. These act as short-term stressors that trigger cellular responses, building resilience and providing a net gain in health.
3. Avoid Immediate Cold Post-Strength Training
Do not use cryotherapy, cold water immersion, or ice packs immediately after strength training, as it may blunt long-term muscle hypertrophy and strength gains. This interference occurs by disrupting the beneficial inflammatory processes necessary for muscle repair and growth.
4. Strategic Cold Timing for Strength
Exercise extreme caution regarding the timing of cold modalities (cryotherapy, cold water immersion, ice packs) when strength training. The first hour after exercise is an important anabolic window, and mistimed cold stress may have deleterious consequences.
5. Cold Water Immersion for Neurotransmitters
Immerse yourself in cold water at 57°F (14°C) for one hour to significantly increase norepinephrine (by 530%) and dopamine (by 250%). These neurotransmitters are involved in vigilance, focus, attention, and mood.
6. Increase Norepinephrine with Brief Cold
To increase plasma norepinephrine two to threefold, either immerse in 40°F (4.4°C) cold water for 20 seconds, or undergo whole body cryotherapy at -166°F (-110°C) for two minutes. Both protocols were shown to be effective when done three times a week for 12 weeks.
7. Reduce Brain Inflammation with Cold
Utilize cold water immersion or whole body cryotherapy to increase norepinephrine, which may serve as a preventative measure to lower general and brain inflammation. This can help attenuate a major contributor to aging and potentially mitigate processes linked to depression and anxiety.
8. Melatonin for RBM3 Activation
Supplementing with melatonin may enhance the activation of the cold shock protein RBM3 and help lower core body temperature. This could potentially aid in the neuroprotective effects associated with cold exposure, such as synapse regeneration.
9. Boost Antioxidant Enzymes with Cryotherapy
Engage in cryotherapy for three minutes at -202°F (-103°C) daily for 20 days to double glutathione reductase activity and increase superoxide dismutase by 43%. This boosts the body’s potent genetic antioxidant systems, which are crucial for mitigating cellular damage.
10. Intense Cryotherapy for Antioxidants
For a robust increase in antioxidant enzymes, elite kayakers used whole body cryotherapy at -248°F to -284°F (-120°C to -140°C) for three minutes a day for 10 days. This protocol increased superoxide dismutase by 36% and glutathione peroxidase by 68%.
11. Frequent Cryotherapy for Antioxidants
To achieve a more robust activation of powerful antioxidant systems like superoxide dismutase and glutathione peroxidase, engage in cryotherapy more frequently. The increase in antioxidant enzyme activity was shown to require multiple sessions.
12. Increase Brown Fat with Cold Air
To increase brown adipose tissue by 37% and non-shivering thermogenesis, expose yourself to air temperatures of 59-61°F (15-16°C) for six hours a day for 10 consecutive days. This can help burn fat and boost metabolism.
13. Cold Water Immersion for Mitochondrial Biogenesis
To increase mitochondrial biogenesis in muscle tissue, immerse yourself in cold water at 50°F (10°C) for 15 minutes, three times a week for four consecutive weeks, after running. This process is regulated by PGC1-alpha and improves aerobic capacity.
14. Boost PGC1-alpha Post-Run
After high-intensity running, expose yourself to cold water (around 50°F or 10°C) for 15 minutes to increase PGC1-alpha in muscle tissue. PGC1-alpha is the master regulator of mitochondrial biogenesis, which enhances aerobic capacity.
15. Enhance Cycling with Cold Water Immersion
To improve cycling performance, elite cyclists immersed in cold water (around 59.5°F or 15.3°C) for 15 minutes, 30 minutes post-training, four times a week for 39 days. This resulted in increased sprint power, repeat cycling performance, and overall power.
16. Improve Endurance with Delayed Cryotherapy
Elite runners experienced a 20% increase in speed and power up to two days later by engaging in whole-body cryotherapy 1, 24, or 48 hours post-hill sprinting. This performance enhancement may be attributed to reduced inflammation and increased anti-inflammatory factors.
17. Boost Tennis Performance with Cryotherapy
For enhanced tennis performance and reduced inflammation, elite players used whole-body cryotherapy at -184°F (-120°C) twice daily (morning and evening) for five days while training in the afternoon. This led to a 4% increase in stroke effectiveness and reduced TNF-alpha.
18. Optimize Plyometric Recovery with Delayed Cryo
To improve plyometric performance (e.g., squat jumps, leg curls) and reduce pain, engage in whole body cryotherapy at -220°F to -319°F (-140°C to -195°C) one hour after exercise. This protocol showed benefits up to 72 hours post-treatment.
19. Reduce Arthritis Pain with Cryotherapy
For arthritis pain reduction, consider whole body cryotherapy at approximately -166°F (-110°C) for 2 to 3 minutes, three times a week for one week. This protocol led to significant pain reduction in patients with arthritis, possibly due to reduced inflammatory cytokines.
20. Local Cryotherapy for Collagen
Apply local cryotherapy to affected tissues to inhibit harmful collagenase activity, an enzyme that breaks down collagen and plays a role in arthritis. It also helps decrease the production of inflammatory E2-series prostaglandins.
21. Cold Showers for Mood
Consider using cold showers as a potential method to prevent and treat depression, as anecdotal evidence suggests cold exposure improves mood. This effect may be linked to a robust release of norepinephrine in the brain.
22. Boost Immune Cells with Cold Water
Engage in long-term cold water immersion three times a week for six weeks to increase lymphocyte numbers, which are important immune cells. Habitual winter swimmers also show higher white blood cell counts compared to non-habitual swimmers.
23. Increase Natural Killer T Cells
Expose yourself to a cold room (around 4°C or 41°F) for 30 minutes to increase natural killer T cell number and activity. Natural killer T cells are a type of immune cell that kills viruses and tumor cells.
24. Winter Swimming for Immunity
Consider engaging in winter swimming, as epidemiological studies suggest an association with a 40% decreased incidence of respiratory tract infections. This may be linked to increased white blood cell numbers.
25. Fish Oil for Fat Metabolism
Consider consuming fish oil, as studies in mice suggest it can increase metabolism and reduce fat accumulation by 15-25%. This effect was shown to be likely occurring through a brown adipose tissue-mediated mechanism.
5 Key Quotes
At the right dose, even things that can be harmful at higher doses can trigger a net gain in resilience.
Dr. Rhonda Patrick
Synapses between neurons actually break down during cold exposure. Synapses are how neurons communicate with each other, and it's how memories are formed. This interesting phenomenon was first observed from studies done on hibernating animals. However, when animals that hibernate warm back up, close to 100% of the synapses regenerate. That's a pretty amazing feat.
Dr. Rhonda Patrick
Low inflammation was the only biomarker that predicted survival and cognitive capabilities across all age groups.
Dr. Rhonda Patrick
The more brown adipose tissue your body has, the more fat your body will burn.
Dr. Rhonda Patrick
You can definitely undermine your gains in the context of resistance training if you're doing cold water immersion immediately after training.
Dr. Rhonda Patrick