FoundMyFitness - #021 How Cryotherapy Affects the Brain, the Immune System, Metabolism, and Athletic Performance

Episode Date: February 12, 2016

Dr. Rhonda Patrick explains how cold shock is a type of hormesis, which is a description of a type of stress that, in the right doses, is enough to shock the body and kick off adaptive processes and response mechanisms that are hardwired into our genes, and, once on, are able to create a resilience that actually exceeds what was needed to counter the initial stimuli. In this episode, you'll discover: (00:00) Introduction (03:09) Cold exposure is good stress for the brain (15:42) Cryotherapy reduces inflammation (23:12) Cold exposure, weight loss, and thermogenesis (30:45) Cold exposure increases antioxidant capacity and  (33:42) How to use cold exposure to enhance athletic performance and recovery  (52:44) Whole-body cryotherapy vs cold water immersion If you're interested in learning more, you can read the full show notes here. Join over 300,000 people and get the latest distilled information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Good day, ladies and gentlemen of the podcast. Today we go deep. How deep you say? 20,000 leagues under the sea deep on the topic of cryotherapy and cold water immersion and ice packs and hibernating animals and winter swimming and everything in between. This podcast has been a long time coming. The topic of cryotherapy is a natural complement to some of the material that I've released previously on sony use or hyperthermic conditioning as I've called it. But if I were to be completely honest, A big motivation for this podcast has been the great deal of enthusiasm some of my friends have for cryotherapy, folks like the great and powerful Joe Rogan, also Kevin Rose, and probably more people than you can shake a stick at. Admit it, you've been thinking about buying one of those

tricked out liquid nitrogen field spaceships yourself having you. Okay, but before we dive in, here's what you need to know. Number one, the topic of cryotherapy is tricky. There's lots and lots of nuance and I end up trying to weave a cohesive narrative from studies that focus on any number of different types of cold modalities. So it's not just whole body cryotherapy. That's the topic of this discussion. This podcast is going to take you all over the place. And we're going to talk about some deep biochemical level stuff because we have to. I try to bring it home and do give some concise conclusions at the end. I hope that helps a little bit. You can skip to the last few minutes if you are feeling impatient. But I don't recommend that. Before we get this show on the road,

there's just two things to know. Number one, this podcast is actually a bird's eye view at a whopping nearly 20-page report on the subject of cryotherapy. I cover a little of everything discussed today on this podcast and maybe a little bit more. And I provide all of my references in the PDF report. To get it, you need to go to foundmyfitness.com forward slash cryo Once again, that's foundmyfitness.com forward slash C-R-Y-O-T-H-E-R-A-P-Y. Cryotherapy. Finally, it's literally impossible that I could spend so much time, weeks, on such an esoteric topic as cryotherapy if it wasn't for the mad love sent to me by so many of you.

First, a special thanks go to the people that support Found My Fitness financially. There's over 700 people that support this content for as little as a dollar a month or less than a cup of coffee and many that support for quite a bit more than that. You can learn more about that at foundmyfitness.com forward slash crowd sponsor. Once again, that's found my fitness.com forward slash C-R-O-W-D-S-P-O-N-S-O-R crowd sponsor. Also, a special thanks goes to those of you that just voice your enthusiasm. by tweeting, Facebooking, and shouting out at me on Instagram or even YouTube comments. You guys are all great. Now, on to the podcast.

Most of us primarily think of stress as a bad thing, and it is. This negative stress called distressed can be the result of or result in inadequate sleep, emotional stress and rumination, poor gut health, and much more. But stress can also be good. good stress can be referred to as U-Stress and can include any number of activities, chiefly among them exercise, but in some contexts probably also things like intermittent fasting, heat stress from using the sauna, and cold stress from things like cold water immersion or cryotherapy. In general, things that fall into the category of U-stress have the quality of being hormetic,

which means that in the right dose, they serve as a short-term stressor that can trigger cellular responses in the body that exceed what is actually needed to compensate for otherwise damaging insults. In other words, at the right dose, even things that can be harmful at higher doses can trigger a net gain in resilience. And this occurs by a variety of different mechanisms. Previously, I have written about, I've talked about the hormetic benefits of heat stress, and in particular, through the use of asana. Some examples of potential benefits might include improving athletic endurance, preventing muscle atrophy, improving insulin sensitivity, increasing neurogenesis, that's the growth of new brain cells, improved learning and memory,

and improving possibly even longevity. So if you want to learn more about the potential benefits of heat stress, you can check out my videos or my podcast, and I also have some PDF reports. However, in this podcast, I would like to instead focus on some of the empirical benefits and mechanisms at play that short bursts of cold exposure, both through cold water immersion and whole body cryotherapy, may have on the brain, the immune system, body composition, your metabolism, exercise performance, recovery, and more. When people think about cryotherapy or cold water immersion, the first thing they think about is perhaps the effect on metabolism or muscle

soreness and recovery, maybe athletic performance or just like the more immediate effects on the body in general. What I find most interesting and maybe a bit more clear cut in some ways are the effects on the brain. It's also an area that just generally interests me more. So let's talk about that first. There is anecdotal evidence that cold exposure improves mood and has been suggested that cold showers may even be used to prevent and treat depression. Let's take a quick dive into one of the possible mechanisms by which cold exposure may actually improve mood. One of the most consistent and profound physiological responses to cold exposure is a robust release of noroponephyran into the bloodstream, as well as from the locus corullius region of the brain. What makes

norapherin so interesting is that not only is it a hormone, but also a neurotransmitter and is involved in vigilance, focus, attention, and mood. The cold induces this robust increase in norapherin in both mice and humans, and it's a response mediated by the sympathetic nervous system, the primary purpose of which is to stimulate the body's flight or fight response. Decreased noropinephrine neurotransmission is associated with inattention, decreased focus in cognitive ability, low energy, and poor mood in general. When noraphanephrine is depleted in people by pharmacological intervention, it causes depression.

In fact, both ADHD and depression are sometimes treated with norapeneprine re-uptake inhibitors, which of course may come with its own set of drawbacks. Noropenephrine also acts as a hormone, and when released into the bloodstream, acutely increases vasoconstriction, which is the constriction of blood vessels. This last part, of course, helps to explain why noropenephrine plays a really important part in our response to cold. By increasing vasoconstriction, we decrease the total surface area by which the blood is able to lose heat to the environment. Let's talk about temperatures. Just how cold do you have to get in order to get that hit of

noropenephrine? There does appear to be a temperature threshold for activating the sympathetic nervous system. For example, cold water immersion at 68 degrees Fahrenheit or 20 degrees Celsius for one hour does not appear to activate noropheneprine release, whereas one hour at 57 degrees Fahrenheit or 14 degrees Celsius increased it by 530 percent and also increased dopamine by 250 percent. Personally, I think dopamine accompanies noraphanphrine quite nicely. Long durations, however, aren't necessarily required for a potent release of noropenephrine. A long-term study in humans directly compared people that immersed themselves in cold water at 40 degrees Fahrenheit or 4.4 degrees Celsius for 20 seconds to those that did whole body cryotherapy for two minutes at minus 166 degrees

Fahrenheit or minus 110 degrees Celsius three times a week for 12 weeks in a row and found that in both cases plasminaupein increase two to threefold, which is around 200 to 300 percent. And this release of noropenephrine didn't seem to be reduced with habituation to cold. Those levels did, however, drop over the course of an hour after the exposure. On a side note, guess what else increases noroponephrine? Heat, as well as lactate, the latter of which is produced by exercise. If you want to learn more about the role of lactate in the brain and how it's produced more robustly upon exercise, you can check out the interview I did with Dr. George Brooks,

who is a renowned exercise physiologist at the University of California, Berkeley, and he's pioneer of the lactate shuttle theory. It's a very interesting podcast. So finally, one last note about norapherine. It also has other profound effects on pain, metabolism, inflammation. This last point in particular may be relevant to the dialogue surrounding mood, since inflammation has the quality of being able to also inhibit serotonin release. But we will return to that topic of pain, metabolism, and inflammation in a moment.

I want to talk about cold shock proteins and a particular one in the brain. In previous articles and videos and podcasts, I've talked. add nauseam about the benefits of heat chalk proteins and how they may even be involved in human longevity. Exposure to the other temperature extreme, cold, also triggers heat shock proteins, but in addition to that, there's a class of proteins that are specific to the cold, coldchalk proteins. Much of what we know about the physiological responses to cold come from research on hibernating animals. Hybernation involves a profound metabolic shift that is driven by the fundamental biological need to conserve energy in the winter. When the

body is cooled, many, many genes are shut down. The exception, however, are genes involved in lipid metabolism, fat burning, and a group of proteins known as cold shock proteins. The expression of these two categories of genes are greatly increased upon cold exposure. One particular cold shock protein known as RNA binding motif 3, RBM3, especially stands out for the purposes of our discussion. RBM3 is found in the brain. brain, heart, liver, and skeletal muscle, and increases in activity greatly, even upon mild cold exposure. 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. The best part is this effect may not be limited to just hibernating animals. It's also been shown in laboratory mice, which are not hibernating animals. Mice that were cooled using a special protocol that included a pharmacological way to dramatically lower body temperature in combination with cold air exposure at a temperature of 41 degrees Fahrenheit or 5 degrees Celsius for 45 minutes experienced about 26, percent loss in synapses in their hippocampus, which is the part of the brain responsible for learning and memory. Once these same mice were allowed to warm back up, they were able to rapidly

regenerate around 93% of those synapses that were lost to the cold. Here's the exciting news. The mechanism by which the loss synapses regenerate was found to be dependent on boosting the activity of the cold shock protein, RBM3. Guess what? This cold shock protein is conserved, in humans. We have it too. The reason RBM3 is necessary for this restoration of synapses is because of the role this cold shock protein plays in binding to RNA to increase protein synthesis at the dendrites, which are a part of the neuron that communicates with the synapses. This enables RBM3, the cold shock protein, to regenerate those damaged neurons. A single exposure to this cold shock protocol at 41 degrees Fahrenheit, 5 degrees Celsius,

for 45 minutes was enough to increase RBM3 in the brain for three days. In mice, when this procedure was repeated once a week for two weeks in a row, not only did it re-blestly increase the expression of RBM3 for those two weeks, but also for an additional six weeks after that. So the natural next question is, what if synapses could be brought back from insults other than the cold? say, for example, traumatic brain injury or neurodegenerative disease. This is where things get really interesting.

Mice that were experimentally induced to have neurodegenerative disease from preon infection when exposed to two rounds of the cold exposure procedure early in life were protected against the loss of synapses, allowing them to have more than twice as many synapses in the brain tissue sampled as the mice that did not get the cold treatment 12 weeks after being infected. The experimental cold stress also prevented cognitive and behavioral deficits that would have normally occurred in these mice as they progressed into later stages of nerd generation. The cold shock they were exposed to increase the expression of the cold shock protein RBM 3 for several weeks, and this delayed the neuronal defects that usually occurred in these

mice. It may be pretty obvious that the ability to prevent the loss of the loss. of synapses is pretty significant and would have huge implications if such a thing could be demonstrated in humans. Losing synapses occurs with normal brain aging and it's accelerated in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease and also after traumatic brain injury. Obviously, there are some novel and very interesting mechanisms at play here, and the ability to protect synapses effectively might have huge implications for these neurodegenerative diseases, as well as brain aging in general.

Let's talk about the human relevance of cold shock proteins. This RBM3 stuff is all very new research, and we really don't know if this effect would occur in the same way in humans. The question is, how much does core body temperature need to be lowered to activate cold shock proteins, including RBM3? It appears that a 2-degree Fahrenheit reduction in core body temperature is enough to induce cold shock proteins, including RBM 3, in human astrocytes. which are a type of brain cell. As an aside, adding some melatonin to the mix may also have an effect of enhancing RBM3 activation even more. And supplementing with it has also been shown to have an effect of lowering core body temperature.

Okay, but to put that into perspective, how achievable is it to lower core body temperature by 2 degrees Fahrenheit? This is actually a very achievable dip in body temperature that qualifies as only very mild hypothermia since anything below 96.8 degrees Fahrenheit is considered hypothermic. By way of example, in one study, young men that stayed submerged in cold water of 68 degrees Fahrenheit or 20 degrees Celsius for one hour, were able to lower their rectal temperature to around 96.9 degrees Fahrenheit, which is around 36.1 degrees Celsius. Or if they stayed in 57.2 degrees Fahrenheit or 14 degrees Celsius water for one hour, they were able to lower their

body temperature to 96.1 degrees Fahrenheit or 35.6 degrees Celsius. This just goes to illustrate how attainable this level of cold shock is. Let's talk about the effects of cold exposure on inflammation and immune function. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out dead cells and tissues damage from the original insult and the inflammatory process and to initiate tissue repair. However, when this process runs awry in the absence of actual biological threat, we are in trouble. Inflammation has been identified as the key driver of the aging process and is associated with most age-related diseases. A recent study looked at a variety of different biomarkers in old people, age 85 to 99, centenarians, which are 100 years old,

semi-supercentenarians, which are 105-plus years old, and super-centenarians, which are superly old because they are 110-plus years old, and found that low inflammation was the only biomarker that predicted survival and cognitive capabilities across all age groups. Earlier, we focused mostly on the effects of noropenephrine in the context of its role as a neurotransmitter. But when studies show it can be increased by as much as fivefold from extreme cold stress, I think it's worth talking a little bit about some of its other roles. One of the roles norepinephrine may also play is in reducing inflammation. Norepinephrine inhibits the inflammatory pathway by decreasing tumor necrosis factor alpha, TNF alpha, a very potent molecule that increases inflammation.

An excess of the inflammatory cytokine TNF alpha has been taken. implicated in almost every human disease, ranging from type 2 diabetes to inflammatory bowel disease, to cancer, to Alzheimer's disease. Believe me, too much of this stuff is bad. In addition to reducing TNF alpha, noropenephrine has also been shown to decrease other nasty chemicals such as macrophage inflammatory protein 1 alpha, which is produced by immune cells when they're activated and may play a role in rheumatoid arthritis. Reductions in systemic inflammation are, for the most part, usually unambiguously positive. One such example that stands out and where this might especially be the case is arthritis.

In a randomized controlled trial, patients with arthritis underwent whole body cryotherapy at around minus 166 degrees Fahrenheit or minus 110 degrees Celsius for two to three minutes, three times a week, for one week, and they had significant reduction in their pain. There may be some, you know, multiple mechanisms that play here, including the cold-induced reduction in inflammatory cytokines mentioned a moment ago. Interestingly, another study found that local cryotherapy, in other words, cooling just the affected tissue, was shown to inhibit harmful collagenase activity on collagen. Collagenase is a enzyme that breaks down collagen and also, you know, plays a role in arthritis. the chryotherapy was also shown to decrease the production of inflammatory E2 series prostaglandins. Some of the pain alleviating effects of cold exposure, particularly in the case of whole-body

cryotherapy, may in fact be due to increase norapinephrine since inflammation itself causes pain. In fact, spinal injection of compounds that induce a release of norapinephrine have been shown to alleviate pain in both humans and animal studies. Let's talk about brain inflammation and mood. Pro-inflammatory molecules such as TNF alpha and the E2 series prostate glandins have been shown to cross the blood-brain barrier and activate the brain's immune cells known as microglia. This is bad. It seems very possible that therapeutic strategies that increase noropenephrine, such as cold

water immersion and whole-body cryotherapy, may be a good preventative. measure, which generally lowers inflammation, and thus facilitates this preventative process of intinuating what is otherwise a major contributor to aging in general. But in this case, the brain in particular. I've also discussed in a previous publication of mine the fact that inflammatory molecules probably contribute to depression and anxiety by inhibiting the release of serotonin from neurons. This may be another implication of using cold shock to reduce neural inflammatory processes. Of course, more direct evidence needs to be shown to link cold shock as a strategy for the potential treatment of mood disorders, but it seems like an interesting and promising

area of inquiry. All of this talk of cold exposure, either from cold water immersion or cryotherapy, lowering inflammation, may have you thinking that you might be better off with fewer immune cells, since they seem to wreak so much havoc. Actually, having a large number of immune cells is generally a good thing. So as long as they're not unnecessarily active, you know, it's a good thing. I already mentioned how inflammation has been identified as a key driver of the aging process. But I also want to point out that the immune system plays another important role in the aging process. Aging is associated with immunosiniscence, non-functional immune cells, and a general reduction in immune cells. In fact, being very long-lived or making it to the age of a super centenarian is associated with having a healthier biological stock of immune cells.

You want to have a good number of a variety of different types of immune cells, but you also want them to be quiet unless there's a good reason to be loud. So how does the cold affect our stock of immune cells? well, it appears to increase them, at least certain types of immune cells. Long-term cold water immersion three times a week for six weeks in healthy males was shown to increase lymphocyte numbers. This is in line with the fact that habitual winter swimmers have a higher number of white blood cells compared to non-habitual winter swimmers. Additionally, another study demonstrated that cold exposure in a climatic chamber of around

41 degrees Fahrenheit or 5 degrees Celsius, increased white blood cell. numbers, including cytotoxic T lymphocytes, which are a specialized type of immune cell that kill cancer cells. Males exposed to a cold exposure, so a cold room that was around 4 degrees Celsius, for 30 minutes, decrease their core body temperature by around 0.4 to 5 degrees Celsius, and increase their natural killer T cell number and activity. Natural killer T cells are another type of immune cell that kill viruses and tumor cells. So all of this may serve to bolster the anecdote shared often among communities of winter swimmers, which is that they experience fewer everyday cold and flu symptoms. In fact, an association has been demonstrated in epidemiological

studies between winter swimming and a 40% decreased incidence of respiratory track infections. So more work needs to be done in order to better understand what the long-term effects of chronic cold exposure are on immune cell numbers and functions to state definitively what this all means, though. Let's talk about cold exposure, weight loss, and thermogenesis. Taking eyes baths has been popularized in part due to the effects of cold on weight loss. One of the body's ways of responding to cold is to increase metabolism, not to produce energy in the form of adenosine triphosphate, known as ATP, but to produce heat to warm the body and in the process burn fat. This process is referred to as cold thermogenesis. There are two types of thermogenesis that occur as a biological response

to cold exposure. The first kind of cold-induced thermogenesis occurs in muscle tissue and involves ramping up metabolism in order to produce heat. This works because metabolism is not 100% efficient and produces heat as a byproduct. This is referred to as shivering thermogenesis because muscle and contractions are what actually increase the energy metabolism. The second type of cold-induced thermogenesis occurs in adipose tissue or fat

and does not involve shivering. It is called non-shivering thermogenesis. This type of thermogenesis is what is really responsible for that quote-unquote fat-burning effect that cold exposure can have. and usually happens after the body has adapted to cold exposure. I can tell you firsthand that the body will adapt. I have done two whole body cryotherapy treatments back to back,

and I shivered a lot the first time, but not at all the second time. So let's talk about non-shivering thermogenesis and brown adipose tissue. This process is partly regulated by norapinephrine, which we already know is robustly induced by cold exposure by anywhere, from two to fivefold, depending on the intensity of cold and length of exposure. Cold-induced norpenephren increases the expression of a protein known as uncoupling protein 1, UCP1, which has the effect of uncoupling the mitochondria, those energy-producing powerhouses of the cell. But what does it mean for mitochondria to be uncoupled? When it is said that

mitochondria are coupled, we are referring to the coupling of the generation of a unit of energy, ATP, to the transport of electrons, which have been derived from the food you eat, that create an electrochemical gradient across the mitochondria, which is negatively charged on the inside and positively charged on the outside. Mitochondria are a little bit like batteries in that sense. When cold exposure activates the uncoupling protein 1, UCP1, this uncouples the electrochemical gradient, meaning there is no longer a negative or positive terminal to the mitochondria. In response, the mitochondria try and reestablish that electrical chemical gradient, quite frantically,

in fact, by transporting electrons, which are derived from the stored fat, called fat oxidation, and producing heat as a byproduct of this process. One of the ways uncoupling protein 1, UCP1, ramps up metabolism is by producing more mitochondria in adipose tissue, which causes a browning effect by converting or transdifferentiating the more common white adipose tissue into its more metabolically active. counterpart brown adipose tissue. You can think about this in simple terms. The more brown antipose tissue your body has, the more fat your body will burn. The reason it's called brown adipose tissue is because each fat cell has more mitochondria per cell. And the mitochondria

make the fat appear brown in color when looking at it under a microscope. Let's talk about cold exposure, increasing non-shivering thermogenesis in humans. It was actually thought for some time that human adults had negligible amounts of brown adipose tissue. Increasingly, however, studies are showing that adult humans do have this special type of adipose tissue that is metabolically active. The fact that we even have brown adipose tissue at all in adulthood actually overturned old dogma that once stated that brown adipose tissue was mostly found only during infancy in humans. In fact, it's now been shown that brown adipose tissue shows an inverse correlation to percent body fat in an individual. The good news is that repeated intermittent cold exposure

has been shown to both increased brown adipose tissue in humans and increase our capacity for non-shivering thermogenesis. Healthy young men and women that were exposed to air temperatures of around 59 to 61 degrees Fahrenheit or 15 to 16 degrees Celsius for six hours a day for 10 consecutive days, increase their brown adipose tissue by 37 percent. And after acclimating, also increased non-shivering thermogenesis by between 11 and 18 percent. It's also very interesting to note that if the brown adipose tissue was sampled during the summer months only, It was shown that it could only be detected in around 25% of the participants compared to around 50% of the participants if brown adipose tissue was sampled during the winter. There you have it.

Maybe the old dogma they were sampling brown adipose tissue in the summer. Okay. So if having more brown adipose tissue, which becomes more active in cold, helps us stave off obesity, then it might be reasonably surmised that being cold, hold would boost our metabolism. In fact, it does. One study done in a small sample of young men showed that cold water immersion up to the shoulders in 68 degree Fahrenheit or 20 degrees Celsius water for one hour increased metabolic rate by 93%.

And one hour at 57 degrees Fahrenheit or 14 degrees Celsius increased metabolic rate by 350%. I'd like to discuss one mechanism by which cold exposure may increase the concentration of brown adipose tissue. One study found that the sympathetic nervous system may be playing a role, a very intimate role, in the production of brown adipose tissue in rats, experimentally blocking beta adrenergic receptors, which norepinephrine act on prevented the production of brown adipose tissue. This relationship is interesting because it might imply that the greater the release of noropenephrine that we can induce from cold, the more browning of our adipose tissue we might expect to occur. Our diet may also be a way we can therapeutically brown our adipose tissue. One study recently showed that consumption of fish oil actually increased the metabolism of mice, reduced their fat accumulation between 15.5.

to 25%, and this was shown to be likely occurring through a brown adipose tissue-mediated mechanism. All right, we are going to change gears again, yes, again, and talk about cold exposure increasing the activity of antioxidant enzymes. One of the side effects of ramping up fat oxidation to burn stored fat for energy is the production of those damaging, pesky reactive oxygen species, known as Ross, that damage nearly everything inside cells, including DNA. This is actually a normal product of energy metabolism and, in a way, is a natural part of just being alive.

How we respond to this damage and mitigate it is ultimately what's important. Reactive oxygen species, by contributing to things like DNA damage and cellular senescence, are a huge component of the very process of aging. They are also a sign of mitochondrial dysfunction. Being able to prevent that damage from occurring or being able to repair it after it does occur are both extremely important for staying healthy and, for one thing, cancer-free.

Interestingly enough, it appears as though exposure to the cold by functioning as a hormetic stressor actually activates very potent genetic antioxidant systems, which are exponentially more powerful than any supplemental antioxidants. For example, young men exposed to cryotherapy for three minutes at minus 202 degrees Fahrenheit or minus 103 degrees Celsius every day for 20 days doubled the activity of one of the most potent antioxidant enzyme systems in the body called glutathlethydrase. reductase and increased another potent antioxidant enzyme called superoxide dismutase by 43%. You know all that liposomal glutathione you've been dosing?

Well, it doesn't do anything if the enzymes that use it are not active. Similarly, elite kayakers that engaged in whole body cryotherapy around minus 248 to minus 284 degrees Fahrenheit or minus 120 to minus 140 degrees degrees. Celsius for three minutes a day for 10 days. Increase the activity of superoxide dismutase by 36% and glutathione peroxide is 68%. That is pretty stout. For those of you that are not familiar with superoxide dismutase, this enzyme is in

your mitochondria cleaning up all that damage that is being produced every second of every day. In other words, it's awesome. It is also important to note that the increase in this analcounter enzyme activity in this case, actually took multiple sessions of the whole body cryotherapy, meaning the more frequent cryotherapy was done, the more robust of an increase in activating these powerful antioxidant systems. Let's talk about cold shock, muscle mass, performance, and recovery. When it comes to cold exposure in the context of exercise, there are two important

factors to look at, the type of exercise being done and the timing of the cold stress in relation to the exercise. Let's talk about timing. Immediately after exercise activity, there is a spike in the production of pro-inflammatory cytokines, which are molecules that activate immune cells and are involved importantly in tissue repair. The production of reactive oxygen species and inflammation that occurs immediately after exercise are actually necessary to activate genetic pathways that contribute to creating more mitochondria, called mitochondria biogenesis, and also play a role in muscle hypertrophy. In fact, macrophages, a type of immune cell that can be activated in,

response to exercise induced inflammation produce high levels of the anabolic hormone IGF1 in response to even slight injury of muscle tissue. There has been some experimental evidence that indicates that these specific immune cells are also likely involved in satellite cell migration. Satellite cells are a type of muscle stem cell that serve as precursors to actual muscle cells, and satellite cell numbers are actually associated very closely with the amount of actual hypertrophy that results from strength training. Let's get back to the exercise-induced inflammatory process. There is an anti-inflammatory response to this inflammation, which begins to peak around

one hour after exercise. At this point, some of the anabolic hormone, such as IGF-1, that are increased with the immune activation seem to also return to pre-exercise levels around one hour post exercise. The anti-inflammatory cytokines help keep our immune system from going overboard. They modulate the activity of the immune cells preventing them from causing excessive tissue damage. You might see where I'm going with this. In the cases where cryotherapy, cold water immersion, or perhaps even the use of ice packs are used immediately after training, it may undermine certain beneficial effects that actually come from having a small dose of inflammation. In fact, there have been some studies that seem to hint at this fact. We'll dive back into that in a second,

but the main thing to remember for now is that the peak anti-inflammatory response occurs one hour after the activity and that some inflammation and immune activation before that point is probably a good thing. The other factor that may influence the outcome of studies looking for the effective cryotherapy or cold water immersion on athletic performance and recovery is the type of exercise we're trying to optimize for. Exercise inflicts stress upon the body, and in response, the body activates many genes and pathways that build resilience and resistance to that stress. What is important to realize is that the type of exercise actually determines characteristics of the adaptation that occurs. So the stress may be predominantly aerobic, such as endurance training,

and may be mechanical, such as resistance training, or it could be a mixture of both, such as pliometrics. Activities that are more characteristically aerobic place a great greater demand on cells to be able to utilize oxygen for the purposes of energy production. In other words, aerobic activities have a greater need of supporting mitochondria. Depending on the nature of the exercise, endurance versus resistance, and the time of the cold exposure, pre-exercise, immediately after exercise, or later, there may be very different and somewhat opposing outcomes. I believe these variables can help explain some of the conflicting evidence regarding the

benefits of cold exposure in the context of performance that have been showing up in the scientific literature and also have been discussed in the media. Let's talk about strength training. Whole body cryotherapy at minus 220 to minus 319 degrees Fahrenheit or minus 140 to minus 195 degrees Celsius done. And this is important. One hour after pliometric exercise, which included squat jumps and leg curls showed improvements in a variety of performance measures up to 72 hours after the cold a treatment. These improvements include power at the start of a squat jump and squat jump workup. In addition, pain measures both at rest and at the next squat jumping session were also improved. The next question is, what happens if cold exposure occurs immediately after

resistance training during that peak pro-inflammatory process. One study has shown that it may actually blunt some of the long-term muscle hypertrophy benefits, at least if you're doing cold water immersion. Men that perform leg presses and squat jumps twice per week and then immediately engaged in 10 minutes of cold water immersion, in other words, at the point of peak inflammation, had only one third of the increases in muscle mass in their quadriceps 10 weeks later compared to those that did not do cold water immersion post-training. In addition, after the 10 weeks of training, muscle strength was significantly lower in the cold water immersion group compared to the control group.

They showed smaller increases in type 2 muscle fibers, which are required for very short duration, high-intensity burst of power. And all of this coincided with the reduction in biomarkers that are usually associated with hypertrophy, including the activation of satellite cells. Basically, if you were looking to make the argument that cold stress, especially cold water immersion, should be avoided after strength training, this last study mentioned would be your holy grail, not only because of the compelling results that the authors demonstrated, but also because they cited other studies that showed similar results with respect to cold exposure and hypertrophy, including some that employed clever investigative methods like having participants do hamstring curls, but only immersing one leg and cold water and then going on to measure the difference in hypertrophy between legs afterwards. However, in every single case, both in this study and all of the similar ones cited, there is one singular unifying theme. The method of cooling, whether we're talking about cold water immersion, icing, or otherwise, was generally applied immediately after training. So that leaves

us with a few open-ended questions. But the most important one is this. Would we still have seen the blunted or reduced hypertrophy training if cold water immersion was done at literally any point other than immediately after strength training? I don't know the answer definitively because no study has investigated this yet. But it's an area I hope future studies will illuminate for us, especially in light of the fact that the occasional cold stress seems to have the possibility of conferring benefits in many other respects. The fact that the first hour after exercise in particular stands out as an important anabolic window, at least in terms of the endocrine response, may also be especially meaningful in the context of cold exposure and strength training. For now, it would seem

extremely prudent in the context of strength training to exercise caution in how and especially when you time any of the various cold modalities, whether we're talking about cryotherapy, cold water immersion, or even the use of cold pecks. We just talked a lot about strength training in the context of cold water immersion. In the case of endurance-related activities, the consequence of cold water immersion and in particular a whole-body cryotherapy are slightly more unambiguously positive. This may be characteristic of the type of adaptations that occur that are more specific to endurance activities, or it could be the fact that cold exposure was not done immediately post exercise in many of the endurance-related studies. In addition to the effect cold

can have on inflammatory processes, cold stress is able to boost mitochondrial biogenesis. The reason this mechanism exists is pretty straightforward. Mitochondria are able to create heat, something you need when you're cold, as a byproduct of energy production. As the powerhouses of the cell, it can be said that mitochondria are pretty darn useful for most of our cells, except red blood cells, which don't have them. However, they're especially important if we want to talk about endurance activity. That's because mitochondria and the density or number of them on a per cell basis affects our aerobic capacity.

mitochondria are what gives us the ability to use oxygen in order to produce cellular energy. and if we do and if we have more of them, it can be said we may be more adapted to aerobic activity. Here's how it works. Cold exposure activates a gene called PGC1 Alpha, which makes more mitochondria in the muscle. This is referred to as mitochondrial biogenesis, and PGC1 Alpha is the master regulator of this process. If mitochondrial biogenesis is the orchestra, then PGC1 Alpha is the conductor. More mitochondria per muscle cell directly transatlantic. leads to aerobic capacity and a single 15-minute exposure to cold water around 50 degrees Fahrenheit

or 10 degrees Celsius following high-intensity running increases PGC-1 alpha in muscle tissue. But even more importantly, cold exposure is actually able to increase mitochondrial biogenesis. Men that were immersed in cold water at 50 degrees Fahrenheit or 10 degrees Celsius for 15 minutes, three times a week, four weeks in a row after running, were able to increase mitochondrial biogenesis occurring in their muscle tissue. Exercise that is highly aerobic, such as jogging or running, has the characteristic of being very metabolically demanding and thus requiring more muscle fibers that are oxidative or oxygen using and fatigue resistant. These types of muscle fibers mostly consist of type 1 or slow twitch muscle fibers. In contrast, muscle fibers that are

specialized for bursts of short duration power, mostly consists of type 2 or fast-twitch muscle fibers, which are muscle fibers that are more glycolytic. Glysis is a process that produces energy that does not require oxygen and makes that stuff called lactate as a byproduct. There is a category of fast-twitch muscle fibers called type 2A that are fast, but also oxidative fibers that are more resistant to fatigue. It turns out that PGC1 alpha as a part of, or in addition to working its magic to trigger mitochondrial biogenesis, yes, it is magic.

Also happens to induce a switch to oxidative fatigue-resistant muscle fibers. Remember that cold stress induces PGC1 alpha and this induces mitochondrial biogenesis. It is interesting to note that getting rid of PGC1-1. alpha in muscle tissue of mice has been shown to shift muscle fibers from the slow twitch type one and fast twitch type 2a muscle fibers that are both oxygen requiring and more resistant to fatigue toward fast twitch type 2b muscle fibers which are more glycolytic fibers required for very short duration high intensity burst of power such as maximal and near maximal lifts and short sprints. In line with this, genetically engineering,

to express more PGC1 alpha in muscle tissue than they normally have causes their muscle cells to show characteristics of type 1 muscle fibers, such as greater resistance to fatigue. In my mind, this suggests that PGC1 alpha mediated mitochondrial biogenesis may be slightly more beneficial for endurance athletes than those focus purely on brute strength. If for no reason other than the fact that it seems to shift muscle, muscle fibers into a configuration that is more conducive to a higher aerobic capacity and more resistant to fatigue. Of course, I can't say that this is absolutely the case because PGC1 Alpha also increases type 2A muscle fibers and type 2 muscle fibers in general do have a higher capacity for

hypertrophy. So now that we've covered a little bit on why endurance activities may be a little bit less likely to experience specific deleterious consequences of mistimed cold stress. Let's talk about what the actual literature says about whole body cryotherapy and cold water immersion in the context of performance enhancements. Elite runners that engaged in whole body cryotherapy one hour, 24 hours, or 48 hours post hill sprinting had a 20% increase in speed and power up to two days later. This 20% performance enhancement post-cryotherapy may be attributed to the reduction in inflammation and increase in anti-inflammatory factors. Too high of levels of pro-inflammatory cytokines post-exercise can result in acute performance

deterioration and muscle damage. This can be problematic for training even several days later, since there may be a greater risk of injury due to residual soreness and changes in muscle function. In fact, it has been shown that elite runners who engaged in whole-body cryotherapy for three minutes at minus 166 degrees Fahrenheit or minus 110 degrees Celsius, performed one hour post exercise and 24 hours post exercise enhanced muscle recovery by decreasing the inflammatory process, so lower I-L-1 beta and lower C-reactive protein levels, and increased the anti-inflammatory process, aisle 1R.A at both 1 and 24 hours post exercise. Another study, including elite tennis players,

also showed performance enhancements that were associated with the reduction in inflammation. Elite tennis players that engaged in whole body cryotherapy around minus 184 degrees Fahrenheit or minus 120 degrees Celsius twice a day in the morning and evening while training in the afternoon. for five days had a 2.5-fold decrease in the potent pro-inflammatory cytokine TNF alpha and a 23% increase in the cytokine IL-6, which has both pro and anti-inflammatory properties and plays an important role in muscle repair. These professional tennis players also experienced a 4% increase in quote unquote stroke effectiveness, meaning they hit more balls in the target zone compared to the players that did not do cryotherapy. Hey, that counts, right?

I mean, maybe it's that norapinephrine helping with focus and attention. These endurance performance enhancements post-exercise, cold exposure may also be sustained over a prolonged time period. Elite cyclists that engaged in 15 minutes of cold water immersion around 159 degrees Fahrenheit or 15.3 degrees Celsius for 30 minutes. post-training four times a week. This training lasted 39 days and consisted of a mixture of low-to-moder intensity road rides and high-intensity interval sessions on an exercise bike. The cyclotis that engaged in the cold water immersion post-training experienced a 4.4% increase in average sprint power, 3% enhancement in repeat cycling performance, and a 2.7% increased

power over the 39-day training period. That sounds awesome. So far, we've covered the effects of various cold exposure modalities on building muscle. But one last area of discussion that I'd like to cover that loosely fits into this area is the topic of muscle atrophy. Quite a bit earlier when we were still talking about some of the interesting brain effects of cold stress. We talked about the effect cold has on the production of cold shock protein, in particular one called RBM3. We also talked a bit about some of the studies done in hibernating animals, which, of course, have to be especially capable at resisting some of the negative effects that can occur during cold. One other interesting aspect of hibernation is the fact that animals that experience this phenomenon, at least in the case of black bears, also experience significantly less muscle atrophy than would be expected for such a long period of fasting and general inactivity.

As you might imagine, this probably is pretty useful for a hibernating animal. there is evidence that black bears actually retain protein balance in their skeletal muscle during hibernation when they're fasting. In other words, they are not generally degrading more proteins than they are making in their muscle tissue, which would cause muscle atrophy. This phenomenon is not limited to bears. It's been shown that hibernating squirrels also experience an increase in RBM 3 in their brain, cardiac, and skeletal muscle. Skeletal muscle cells from mice that have been engineered to have

increased levels of RBM3, have improved muscle cell survival and even larger muscle cell size after being exposed to a brief period of cold shock. RBM3 is clearly playing an important role in the muscle in multiple organisms and may be serving as a generalized mechanism for decreasing atrophy. This would also explain why RBM3 is the most highly elevated, is the most highly elevated gene in the muscle tissue of black bears during hibernation. RBM3 is not the only cold inducible protein that is associated, at least in animal studies, with a reduction in muscle atrophy. PGC1 Alpha, the master regulator of mitochondrial biogenesis we talked about earlier, like RBM3 has also been shown to be increased in humans under conditions of cold

stress. It has been shown to protect against sarcopenia, which is age-related muscle loss, and metabolic disease in mice that were genetically engineered to make more of it. While it's important to note that all of these studies that I've discussed in the context of muscle atrophy are animal studies, it shows promise when you see a similar effect conserved across multiple different species of animal, because it hints at the fact that this mechanism may not, may actually extend to us as well, and is probably not a point of specialization, at least not for one specific species. Finally, one last note on this subject.

Heat shock proteins, otherwise known as HSPs, can also be induced to some extent by cold, and I've discussed them in a previous video, podcasts, articles, when I talk about the science of a sauna use. I talk about how heat stress and the concomitant elevation of heatchalk proteins has been demonstrated to greatly increase muscle regrowth by 30% in rats during the two-week reloading phase that followed a week of forced immobilization. We've talked a lot about cold water immersion and whole-body cryotherapy and cold packs and hibernation and everything in between an effort to be comprehensive

and see where we can make inferences. However, what we have not done is more directly try to compare whole body cryotherapy and cold water immersion. In terms of application, this is actually a really important point. So the million dollar question is, is whole body cryotherapy the same as cold water immersion? The answer is probably not. If we dive into the science, we can see that there are three factors that really differentiate whole body cryotherapy from cold water immersion. And all of them have to do with how effectively each technique lowers core body temperature. But I also want to point out that in addition to these three factors, which we will discuss in a minute, is the fact that people can remain in cold water for longer durations than cold air cryo chambers,

and this may affect how robust the cold shock response is. These three factors include thermal conductivity. This is essentially how well heat is extracted from the body. How much of the body is exposed to the colds of surface area. And finally, the temperature gradient. In each of the mediums, ice, water, and air, they all have different properties that affect how well heat is extracted from the body. Starting with the first factor, thermal conductivity, how well heat is extracted from the body.

Ice has the greatest capability to extract heat from the body, followed by cold water and finally air. Cryotherapy is slightly less effective at heat transfer since it only uses error. The second factor, surface area, also plays a role in cooling the body. In the case of cold water immersion, the surface area of cold water covering the body really depends on the protocol and can vary from submerging just the legs or it can involve submersion all the way up to the shoulders. In any case, your head will usually not be submerged in the water.

This is very different from a cryotherapy chamber where the entire body, including the head, is exposed, although some cryochinks do not expose the head to the cool air. Finally, the third factor is the temperature gradient, which is the actual temperature difference between your body temperature, 98.6 degrees Fahrenheit or 37 degrees Celsius, and the modality being used to suck the heat right out of you. This is really where cryotherapy shines because the air temperatures can be as cool as minus 289 degrees Fahrenheit or minus 170 degrees Celsius. Probably even colder, but that's cold. Lastly, another important factor, to consider when comparing cold water immersion differences with exposure to cryogenic temperatures

in the air is the fact that people can stay submerged in cold water for much longer time periods than cryotherapy air chambers. So what's the final word? Well, what is clear is that there is a very consistent and very robust release of norepinephrine in the brain and the body, both in cold water immersion and whole body cryotherapy. There have even been studies directly comparing the norahepine response to cold water immersion. So the whole body submerged for 20 seconds in 40 degree Fahrenheit water with whole body cryotherapy, two minutes at minus 166 degrees Fahrenheit, and found that they are more or less identical, at least in their response, norepinephine response. Now, if you were to stay submerged in that cold water for an hour, as opposed to just 20 seconds,

we know that noropenephrine would increase 500%, which brings us back to the point that exposing the body to cold for prolonged periods may have a more robust effect. Other than that, I'll leave it as an exercise to the reader and listener to make their own value assessment based on the information at hand. It's probably not worth overthinking too much at this point. We've covered a lot. So I think now is as good a time as any to take a step back and ask, what's the big picture message here?

In other words, what does it all mean? I think there are many key takehomes from all of this, and I'll try to summarize just a few. Number one, cold shock shows some interesting promise for helping diseases of nerd generation through a specialized cold shock protein known as RBM3. Will we be taking people and putting them through super traumatic freezing temperatures in the future to prevent Alzheimer's disease? I don't know. but the fact that this neuroprotective synapsing fixing effect happens in mice is a very good sign

and hints at some really profound things we may find out in the future are applicable to humans as well. Number two, noropenephrine, which can go up a huge amount from a variety of different cold stressors, has some pretty interesting properties and is a very versatile neurotransmitter and hormone. We need it for vasoconstriction as a part of the body's dynamic response to cold, but it also is an anti-inflammatory and also improves focus and attention. For this reason, it may have special relevance for diseases of inflammation like arthritis, as well as mood and even depression. Number three, giving yourself short bouts of intense cold stress may be applicable if you

have some degree of chronic pain because of the analgesic effect, which may also be partly mediated by, you guessed it, nor epinephrine. Number four, there may be some truth to winter swimming improving immune function in regular practitioners. Number five, in contrast to old dogma, adult humans have brown fat and exposure to cold increases it. Brown fat generally decreases as we get older, especially if we're obese. Having more of it, however, is associated with trending towards a lower body fat percentage,

and finally, the amount of brown fat is directly affected by our exposure to cold. Cold water immersion can definitely increase brown fat, but sulking cold air, which means whole body cryotherapy is probably also effective for this purpose. Number six, using cryotherapy and cold water immersion in the context of exercise is sort of complicated. You can definitely undermine your gains in the context of resistance training if you're doing cold water immersion immediately after training. In other contexts, however, there may be improvements in performance as well. We still have some unanswered questions and very interesting points surrounding this. I'm hopeful that the more deleterious effects will be, will turn out to be

mostly constrained to the hour-long window of time immediately after training. But I'm not really sure. We need more studies to say for certain. Number seven, when comparing whole body cryotherapy and cold water immersion, they're probably pretty similar, at least in many of their hormonal responses. One key point of difference is that it is possible to stay in cold water for a longer period of time than it is to stay in a cryotherapy chamber, which could put you in danger of local tissue damage, such as frostbate. Do it strikes your fancy until better evidence emerges.

As a cautionary note, it is prudent to consult a physician before beginning a new workout program, and this is no less true for activities like cold water immersion, winter swimming, or cryotherapy. This podcast and document is for informational purposes only and not medical advice. Use this information at your own risk. Additionally, if you have coronary, risk factors or other heart-related risk factors, it is especially important that you console a medical position before attempting anything discussed in this article and podcast, but perhaps, especially before doing contrast therapy, going from rapidly very hot temperatures to very cold temperatures.

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