CRYOTHERAPY: What Does the Data Say?

I've gotten a lot of questions about cryotherapy, how does it work? what does it actually do? Does it help with....

(Find a full podcast episode on Cryotherapy here)

Cryotherapy has been said to:

• Improve immune function
• Reduce inflammation
• Increase stem cell production
• Increase/activates BAT
  • Downstream effects
• Improves heart health
• Decrease pain
• Activate sirtuins in BAT
• Activate cold shock proteins
• 300-600 Calories per visit

But what does the science say?

Questions:

1. How does Cryotherapy improve inflammation?
2. How does cryotherapy help the immune system?
3. Can cryotherapy help with weight-loss or body maintenance
4. Is it bad for your heart?
5. Can Cryotherapy help with pain relief?
6. Will it help with actually healing pain/problems?
7. What does it do for StemCells?
8. Can it help with athletic performance?

Risk:

• Cryotherapy - not much risk shown if used and screened
• Cold water plunge: After drop
  • prolonged cold exposure can cause the cold water in the limbs to overwhelm the warm water in the core organs and cool off the blood too fast and cause heart arrhythmias. - We don't see this is cryotherapy.

Science:
Norepinephrine: is a hormone and neurotransmitter involved in focus, attention and mood. Cold induces a Robus increase in NE. NE increases vasoconstriction for vascular treatment etc.

RBM3 is a cold shock protein. Cold boosts the activity of RBM 3 - RNA binding motif 3 (RBM3)- which plays a role in restoring damaged synapses after cold therapy. THis is potentially excited because we can stimulator a repair of damaged nerves, help with neurodegeneration issues and improve long term protection of synapses if we have a family history of dementia, alzheimers etc.

Inflammation:
NE inhibits the inflammatory pathway by decreasing TNFa a potent inflammatory molecule. TNFa has been implicated in most disease, diabetes, ibd, cancer etc. Somewhere between 2-3x/week appears to change these markers in humans.

Soft tissue repair:
Cryotherapy has been shown to inhibit collagenase activity that breaks down collagen. This can be a good thing if we have had a soft tissue injury to ligaments, muscles, tendons etc. I believe this is where we see some of our patient's speed through the healing process so much faster with the addition of cryotherapy.

Pain:
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 three times a week for 1 week had a significant reduction in pain. Some of the pain alleviating effects of cold exposure, particularly in the case of whole-body cryotherapy, may, in fact, be due to increased norepinephrine since inflammation itself causes pain. In fact, spinal injection of compounds that induce a release of norepinephrine has been shown to alleviate pain in   human and animal studies

Immune function:
Immunosenescence (Nonfunctional immune cells) -
Cryotherapy - increases certain types of immune cells like white blood cells, cytotoxic t lymphocytes that kill cancer, natural killer T cells increased in number and activity in one study a cell type that kill viruses and tumor cells. This may explain why studies done on winter cold water swimmers lowered their incidence of infections by 40%.

Weight Loss - Metabolism:
Cold causes something called cold thermogenesis - this is where our body increases metabolism to produce heat. One type of cold thermogenesis is non-shivering thermogenesis basically where your muscles are not contracting to produce heat.
If we experience this, it can cause an increase in something called UCP1 uncoupling protein 1 that through some reactions in the body can convert white adipose tissue to brown. This is great because the benefits of BAT are widespread, and the harm of WAT are just as widespread.


Possible benefits of batokines:

• Heart—cardioprotection via FGF21 and IL-6
• Pancreas—preservation of beta cells
• Liver—fatty acid oxidation, so presumably it might lower fatty liver, lower white adipose tissue, so you have more lipolysis and more glucose uptake
• Inhibition of myostatin—potentially the increase in brown adipose tissue activity inhibits myostatin 

Antioxidant/Detox:
A side effect of using oxygen for energy is the production of exhaust:  those damaging reactive oxygen species (ROS) that damage nearly everything inside cells, including DNA by contributing to things like DNA damage and cellular senescence, are a huge component of the very process of aging.
Studies show 20 sessions doubled the activity of one of the most potent antioxidant enzyme systems in the body called glutathione and increased another potent antioxidant enzyme called superoxide dismutase by ~43%.
Another study showed 10 days/sessions increased the activity of superoxide dismutase by 36% and glutathione peroxidase by 68%.
Superoxide dismutase is the enzyme is in your mitochondria cleaning up all that damage that is being produced every second of every day.
It is also important to note that the increase in antioxidant enzyme activity, in this case, 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 enzymes.

Performance:
Activities that are more characteristically aerobic place a greater demand on the 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 vs. resistance) and the time of the cold exposure (pre­exercise, immediately after exercise, or later) there may be very different and somewhat opposing outcomes.
Strength: Strength Training Whole body cryotherapy at ­220 to ­319°F (−140 to −195 °C) done 1 hour after plyometric exercise (squat jumps and leg curls) showed improvements in a variety of performance measures up to 72 hours after the treatment. These improvements include  power at the start of the squat jump, and squat jump work up. In addition, pain measures (both at rest and at the next squat jumping session) were also improved.
blunted? -Men that performed 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 ⅓ of the increases in muscle mass in their quadriceps 10 weeks later compared to those that did no cold-water immersion post­training.
Endurance whole-­body cryotherapy is slightly more positive. This may be characteristic of the type of adaptations that occur that are more specific to endurance activities Cold increases mitochondrial biogenesis.  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 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 .
Aerobic activity uses a lot of oxygen causing a lot of ROS so the immune changes we talked about may have something to do with the endurance improvements, but we definitely see good improvement in endurance training. Most of the research showed it being done after runs or endurance. This increased mitochondria in those cells so they could produce more energy easier.
Performance improvement: Elite runners that engaged in whole body cryotherapy 1 hour, 24 hours, or 48 hours post hill sprint running 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.

The Thousand Mile High Summary  
Patients:



We've covered a lot, so I think now is as good of a time as any to take a step back and ask  what's the big picture message here. In other words, what does all of this mean? I think there's  many key take homes from all of this. I'll try to summarize just a few.    
● ONE. Cold shock shows some interesting promise for helping diseases of  neurodegeneration through a special 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? I don't know, but the fact that this neuroprotective, synapse 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.  
● TWO. Norepinephrine, 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 part of our body's dynamic response to  cold, but it is also anti­infammatory. For this reason it may have special relevance for  diseases of inflammation, like arthritis, as well as mood and even depression.  
● 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… norepinephrine.  
● FOUR. There may be some truth to winter swimming improving immune function in  regular practitioners.  
● 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. Cold­water immersion can definitely increase brown fat, but so can cold air, which  means whole body cryotherapy is probably also effective for this purpose.  
● SIX. Using cryotherapy and cold­water 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 cold­water immersion immediately after training. In other contexts,  however, there may be improvements as well. We still have some unanswered and very  interesting questions surrounding this. I'm hopeful that the more deleterious effects 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!  


Cold exposure and immune: https://pubmed.ncbi.nlm.nih.gov/10066131/
Changes in inflammation following exercise: https://pubmed.ncbi.nlm.nih.gov/21829501/

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