Cold-Water Immersion and Cryotherapy: Neuroendocrine and Fat Browning Effects

Doctor Rhonda Patrick here today we are going to talk about the brain and metabolic effects of cold exposure. We all want to reduce stress and make our lives easier, but is that always the best approach? What if the best medicine might just be a little low dose stress? This idea harnesses hormesis, a biological phenomenon where a low dose, short duration stressor, in this case cold temperatures, triggers a cascade of adaptations that protect us against future larger stressors, basically preconditioning our bodies against stress. This isn't a new idea. Humans have used cold exposure often with the expectation that it promotes health for centuries.

But habitual cold exposure can have far reaching beneficial effects on our bodies, metabolic health and possibly brain function, many of which converge on a chemical released in response to the cold norepinephrine. Produced in the adrenal glands and central nervous system, it can act as both a hormone and neurotransmitter. Because of norepinephrine's unique effects, cold exposure may influence aspects of physiology relevant for fighting metabolic related diseases and parameters of brain function associated with mood neurodegeneration and depression. And studies in both mice and humans have shown that cold water immersion increases levels of PGC1alpha in skeletal muscle.

PGC1alpha is a protein that regulates mitochondrial biogenesis, the production of new healthy young mitochondria increased. Mitochondrial biogenesis is an adaptation to exercise and is associated with greater aerobic capacity and a lower risk for developing many diseases such as Alzheimer's, Parkinson's and type 2 diabetes. When acting as a hormone, norepinephrine causes your blood vessels to constrict, which helps you retain heat. But retaining heat isn't the only way our bodies maintain their temperature. We can also produce heat, a process called thermogenesis. There are two types. Shivering Thermogenesis, as the name would imply, involves shivering to produce heat. It relies on the energy produced by ATP hydrolysis during muscle contractions to generate heat.

Useful, but somewhat inefficient. But the body also has a more efficient way non shivering thermogenesis is direct metabolic heat production. And norepinephrine plays an important role here too. It acts on key proteins such as UCP1 in fatty tissue. These proteins disconnect the normal electrical processes within our mitochondria that produce chemical energy and instead allow them to directly produce heat. But there's a catch. Not all fat can do this equally. This type of thermogenesis is mostly a quality of a type of fat known as brown fat, so called for its darker coloring, which reflects the overall mitochondrial density of the tissue. Scientists once thought brown fat was only present in newborns to provide protection against body heat loss.

But we've since found it in adults as well, particularly following cold exposure. And that is because other types of fat can take on thermogenic characteristics of brown fat, a process that also involves mitochondrial biogenesis that is regulated by, you guessed it, the release of norepinephrine in response to cold. How much can we increase brown fat activity? A study in which healthy young men wore a cooling suit at 50 degrees Fahrenheit found that their brown fat volume increased 45% from baseline. Why does this matter? Because the oxidative metabolism in their brown fat increased more than twofold, suggesting that cold exposure can increase energy expenditure, which could have metabolic benefits.

Another team of researchers exposed participants to a temperature of 63 degrees Fahrenheit for two hours a day. Over six weeks, their thermogenesis increased by about 58% and they saw a mostly negligible decrease in fat of about one and a half pounds. The control group experienced none of these changes. But there's further evidence to suggest that cold induced brown fat activation affects metabolic health, improving glucose and insulin sensitivity, increasing fat utilization and protecting against diet induced obesity. One study looked at men who underwent prolonged cold exposure in a cooling vest. Their energy expenditure increased 15%, but only among those who had detectable brown fat. Roughly one third of this increase was due to oxidation of plasma derived glucose.

When the men received an infusion of glucose, only those who had detectable brown fat showed a further increase in glucose use. That's important because it indicates that brown fat plays a role in glucose utilization, essentially providing an alternate pathway for glucose. And in fact, for healthy young people, this type of glucose uptake after cold exposure and exceeds the insulin stimulated uptake rate in skeletal muscle, making brown fat an interesting potential therapeutic target for the treatment of metabolic disorders. So it's clear that acting as a hormone, norepinephrine released by cold exposure can have wide reaching positive effects on our bodies. But it can also act as a neurotransmitter and may influence brain function.

Animal studies have found that chronic cold exposure also promotes the release of norepinephrine from from the locus coeruleus region of the brain. In the brain, norepinephrine is involved in vigilance, focus, attention and mood. Low levels are associated with decreased attention, cognitive ability, energy and poor mood. Norepinephrine depletion may even lead to depression. In fact, both ADHD and depression are sometimes treated with norepinephrine reuptake inhibitors, which block the reabsorption of norepinephrine, increasing the levels around our neurons. But these drugs carry some risks. Increasing norepinephrine through cold exposure, while not completely risk free, shows promise as a way of addressing these aspects of mental health.

For example, in a prospective randomized control trial, participants received 10 sessions of whole body cryotherapy, short exposure to extremely cold air in addition to antidepressant medication. Compared to the control group who were exposed to cold but not cryogenic temperatures, the participants showed marked reductions in their depressive symptoms, an improvement in their quality of life, mood and acceptance of their diagnosis. Sounds pretty good, right? So how can you try out cold exposure for yourself? The most common methods are cold water immersion and cryotherapy. They differ in their ability to reduce body temperature but but they both seem to induce a robust release of norepinephrine.

In one study, women either swam in 35.6 degree Fahrenheit water for 20 seconds or underwent cryotherapy at temperatures 166 degree Fahrenheit for two minutes. They did this three times per week for 12 weeks. Both groups of women showed two to threefold increases in their circulating norepinephrine after each exposure session. And temperature does matter. In a study where healthy young men underwent one hour head out immersions in three different temperatures of water, only the coldest of the three increased norepinephrine by 530% and dopamine by 250% compared to their levels before immersion. Not only that, but the coldest water increased their energy expenditure by 350% and compared to pre immersion levels. Duration matters too.

A separate study found that neck deep immersion in 50 degree water for up to an hour increased norepinephrine. The longer they were submerged, the bigger the response. So exposing the body to cold for prolonged periods may have a more robust effect on norepinephrine release. However, other studies have still found significant effects with less time. One I previously mentioned had women immersed themselves in 35.6 degree Fahrenheit water for only 20 seconds and still saw big jumps in plasma norepinephrine. While we can't strictly equate all adaptive benefits on that basis alone, at the least we do know a lot can happen in even just 20 seconds, which is encouraging for those of us that just need an excuse to get our feet wet.

There's still a lot to learn about cold exposure's effects on health and and the mechanisms that drive them, but the early evidence is promising. For a comprehensive overview of the science, be sure to check out our topic article on cold [email protected] I'm Dr. Rhonda Patrick and I'll catch you next time.