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Whole-body cryotherapy as adjunct treatment of depressive and anxiety disorders (nih.gov)
34 points by amelius 14 days ago | hide | past | web | favorite | 49 comments

> The subjects in the study group were additionally treated using a cycle of 15 visits to a cryogenic chamber carried out daily from Monday to Friday.

In a 3 week study of treatment for conditions where social withdrawal is a critical element, one of the groups had three weeks of additional, mandated social participation.

One of these groups also had a unilateral, massively higher level of education (approx 1/3 of the intervention group was college educated; less than 5 percent of controls were). To the extent that education correlated to SES strongly correlates to positive health outcomes, that’s not a small difference.

This is an interesting pilot, and I’d be in favor of a reasonable follow-up study. But in itself it doesn’t show jack.

It's part of a respectable body of science researching the effects of heat shock protein release on autoimmune driven conditions. Both hyper and hypothermia cause the release of heat shock proteins, which trigger the immune system to dial down inflammation. This is co-option of the body's natural process for recovery after serious illness, where heat shock proteins are released in response to natural fever, triggering tnf-regulator cells and other processes.

The twist is that we are starting to appreciate and investigate the use of heat shock protein release induction directly on mood disorders. A sizeable portion of depressed people, specifically the anhedonic subtype, respond to treatments that target the immune system, or it's effects on the brain. These people tend not to respond to most classes of antidepressants, aka treatment resistant depression, or cognitive therapies, since (on the whole) you can't think your way out of an autoimmune disease.

There are a number of physiologically plausible mechanisms underlying various plausible therapies that turn out not to have clinical effects. That is why we test them empirically.

And this study was not structured to plausibly prove clinical efficacy, regardless of how plausible you feel the underlying physiological mechanism is.

So, I haven't seen this before. So I thought I'd take a look:

Sources 1 and 4 are both from the "FoundMyFitness" folks. One is a YT video, and the other is a layman's article that, from what I see, is an argument including things like "here are various physiological routes that may play a role. Therefore, it works." A lot of pointing at mice models.

Almost no reference to human studies at all. I went through it looking for what they referred to as evidence in humans, and found citations like Shevchuk 2008 ("Practical testing by a statistically insignificant number of people, who did not have sufficient symptoms to be diagnosed with depression, showed that the cold hydrotherapy can relieve depressive symptoms rather effectively"), and Gordh 1998 (an assessment of administration of 10 patients receiving epidural clonidine for pain relief, not cryotherapy), and Pertovaara 2003 (an assessment of rats getting fadolmidine, an alpha-2 agonist like clonidine).

Your link #2, Tricas-Moreno 2016, is a case study of a single young athlete with ankylosing spondylitis receiving multimodal physical therapy - "with orthopedic joint mobilization, dry needling, exercise, and whole-body hyperthermia." Not that a single case report actually means anything, but for what it's worth, he received the opposite of cryotherapy.

And source 3, Pae 2007, was a descriptive study showing that certain genetic variants for inflammatory mediators were associated with better or worse responses to antidepressants ("In conclusion, genetic variants within the genes coding for HSP-70 family proteins may affect the action of antidepressants and thus their therapeutic efficacy,") and that these markers went up or down in response to antidepressants, not that the presence of inflammation itself was causal. Nor was there any empirical assessment at all of cryotherapy as a treatment modality.

So, to summarize: Source 1 and 4 seem to be some layman's stuff that, at best, points at some studies that suggest a possible mechanism, at the 10,000-foot level of "inflammation happens, it might be involved with depression, if you do things that might mediate some types of inflammation, you might mediate depression." Source 2 is a physical therapy case study of a guy that got the opposite therapy. Source 3 elaborates slightly on "inflammation may play a role in depression."

None of this at all shows any clinical efficacy, whatever. None of these are clinical studies of cryotherapy in depression.

Sorry, that was the wrong ankylosing spndylitis reference. The last link, like the first, I passed on because it is full of references to primary articles.

In any case, you don't seem to have the background in rheumatic diseases to evaluate any of this, and I don't have the time to pass on the knowledge I've garnered, as a sufferer, and also a life sciences engineer working on autoimmune and genetic engineering problems. Consequently this has already devolved into a Joe Rogan-style internet argument.

If this stuff is important to you,keep watching the news, there's a lot of good research that's going to reach outside academia in the next couple of years, regarding hyper/hypothermia, heat shock proteins, and autoimmune and mood disorders.

Your first and last links didn't have references to primary articles of clinical assessments. Your third article was more of the same. Your second article was just funny because it pointed to the opposite therapy.

> as a sufferer, and also a life sciences engineer working on autoimmune and genetic engineering problems.

I wish you could join me in the irony of being a physician with an autoimmune disease being told "you don't seem to have the background" to evaluate your citations.

That is ironic. Unfortunately, according to my oncologist friends, it's also commonplace.

You reviewed what I posted with an aim to proving me wrong, not expanding your knowledge, and then prove me wrong. Kind of a terribly attitude in a physician, and really self-destructive to those dealing with autoimmune disease.

"You reviewed what I posted with an aim to proving me wrong"

As an uninvolved reader I had the opposite impression.

How is the detail "15 visits to a cryogenic chamber carried out daily from Monday to Friday" to be interpreted?

They did 15 cyrotherapy sessions total, at a rate of 3 a day?

The study lasted three weeks, encompassing three business weeks of Monday - Friday, for a total of 15 business days. The cryotherapy group came into the office for a chill every one of those 15 days.

I started cryotherapy last year. I went every day for 30 days. I know go about once a week. I'm headed to hot yoga followed by cryotherapy for the extra shocking effect.

Anecdotally, I find it helps me recover from training. This is probably too much information, but I find it is excellent for the gentlemanly bits down under.

I'm 39. Give me more of anything that makes me feel 19 again.

> I find it is excellent for the gentlemanly bits down under

Do you mind being a little more specific? Increased sex drive?



Testosterone replacement therapy.


Side note: this is somewhat similar to the old methods of treating mental patients.

Ice-cold baths were used to treat mental patients who showed signs of low mobility and lethargy or manic-depressive psychoses. Often against their will.

I used to _hate_ cold showers but I now finish off my showers every morning as cold as my shower can go. If you have low energy levels in the morning I can't recommend it enough.

It's not pleasant for sure but the mood improves significantly afterwards

To what extent is either a cold shower or an ice bath similar to the cryotherapy used in this experiment?

"Cryotherapy" as used in this study is basically being nude in REALLY cold chambers; like -120 or -160C for fairly short periods of time. I have no idea how they came up with the idea of making the chamber that cold. I suppose someone looked at extreme saunas and tried the opposite.

You probably know about Wim Hof and the various sports/human performance things involving cold (no doubt as touted on Joe Rogan as every fruity health fad seems to be). Personally I think it probably does do something, though every individual reaction is different. I've always done the cold water at the end of the shower James Bond thing. I recently moved from the Bay Area where it is 70F all year to a place where it was recently -30F with the wind chill. The cold seems to fill me with vigor; love it. Love the Sauna as well. Generally speaking I think the human organism thrives best with a little hormesis.

>The cold seems to fill me with vigor; love it.

Wouldn't that just be a "you're-about-to-die-adrenaline" kind of response?

Whatever it is, it is not adrenaline.

There's nothing quite like the first deep breath going outside on a 0F day. Vigor really is the right word. Another would be clarity.

Unless you have the mindset of "I hate the cold, this is terrible" then it's just suffering.

Not sure about this study but my experiences are similar to yours. I switched away from the hot showers completely about 2 months ago for three reasons.

I started getting itchy skin and no amount of moisturizer helped. Now I need very little moisturizer. I think is is a gain.

Cold water immersion also helped me with fidgety legs. I tried with simple 10 seconds of cold shower at the end of bath but then liked it and increased it to 10 minutes of immersion on good days.

After a stressful day at office, a cold shower helps with sleep.

Yeah, that's dangerously cold: corneal, lip and ear damage territory. Sounds like "unpleasant must be magic panacea" department unless proven with good studies.

Often these things are containers you get into that your head is not in.

Your point is well taken, but at least those 3 bits are probably safe from these types of containers.

There is a collar around your neck so only the body is in the cold. The head is warm.

I think you wear masks and stuff like that to protect sensitive parts

The body builds a pocket of air around it so if there's no breeze like outside and one stands still it takes colder temperature to feel cold

I always thought the coldest you could possibly feel safely was in moving ice water.

Good question. Was it ever tested so far ? I believe not.

My guess is that it is near as efficient as a cold shower. So you can go for Wim Hof method. It costs almost nothing comparatively.

As far as I am concerned, being hit with mild anxiety for more than 10 years, WBCT (3 minutes in a giant fridge cooled at -113° C) which I tried for 10 sessions didn't improve my symptoms. My physical recovery was a bit better.

To me it feels the same but it's easier to get into the cryotherapy chamber for 3 minutes. I find cold showers really tough.

If you look past the sciencese of "short-term adjuvant treatment for mood and anxiety disorders", basically:

"It feels fun to shock your body with cold"

It sounds interesting, but I'm not quite sure how to feel about the conclusion that the effects here may be short-term. Anxiety and depression are generally big picture/long term issues for people rather than acute instances.

Not randomized, not blinded. Likely to be a powerful placebo response. Awaiting the companion article, Steam bath as an adjunct treatment.

Also note that the 'nih.gov' link probably unduly impacts credibility - it's just the pubmed central site, not an NIH-supported trial.

Yup. :/ I'd like to see the p-value on a double-blinded, randomized trial of sufficient sample-size. (I don't know how you blind cryotherapy since it's presence would be obvious except to vary the temperature and look for nicely-moving data signals.)

Umm, what about the huge adrenalin and testosterone rush that you get?

> Apart from activating the body’s system of temperature regulation, there is also a hormonal response, which increases body metabolism and the concentrations of adrenaline, noradrenaline, adrenocorticotropic hormone (ACTH), cortisone, pro-opiomelanocortin (POMC), and β-endorphins in blood plasma as well as male testosterone levels

The most awesome head high I've ever experienced was jumping into a icy creek after hiking all day on a hot spring day.

> Umm, what about the huge adrenalin and testosterone rush that you get?

Perhaps it is important. Perhaps it has a negligible effect to cure/improve the condition of the patients.

(You can get adrenalin and testosterone rush seeing an horror movie. Does it also work as a cure?)

If the study is not double blind you have two problems:

1) People want to be cured and want to be nice to the doctors that are making a huge effort to cure them, so they lie. The people don't lie on purpose. They are just a little optimistic and give involuntary an inaccurate answer.

(The effect is bigger in relative questions like "In the scale from 1 to 10, how much does it hurt?" than in objective questions like "How many fingers do you still have?".)

It's difficult to "blind" the patients here, because the placebo treatment must be as indistinguishable as posible for the patients. Perhaps they can put half of the people at -160°C and the other half at -10°C or -20°C. I guess people will not notice the difference if they live in a tropical country. Let's hope hat the effect is triggered in one case and not in the other.

2) Medics want to find a cure, save the humanity, get a Nobel prize, don't see they effort wasted, so they lie. The medics don't lie on purpose. They are just a little optimistic and give involuntary an inaccurate evaluation.

(Also the effect is bigger in relative question than in objective questions)

It's easier to blind the medics using one team to administer the treatment and other to evaluate the outcomes.

3) (There is always a 3.) The threated patients got 15 visits to the medical center to get the treatment. Does the effect come from the freezing or just for the 15 nice trips and warm welcome in the medical center? Did the patients take an additional bath before going to the treatment (to avoid being naked and dirty)? If your control group is not almost equal to the study group, it's difficult to understand what made the difference.

4) And remember to use a randomized group, to avoid cherrypicking the good candidates and putting in the control group the unsolvable cases.

I seldom do it but after I jump into icy cold water I get a very good mood for the rest of the day.

Look up the stuff Wim Hoff “Ice Man” is onto. Hot/cold shocks of any form are super fascinating.

I'd wager heat shock protein release is doing more for those with biologically depression.

I dunno my theories here have been aging pretty well:



I'm sure there is a placebo aspect, but I wouldn't underwrite the anti-inflammatory component or the sensory stimulation component either.

The anti-inflammatory effect of heat shock protein release is well documented and understood. It's the trigger your immune system uses to start recovery after a fever.

As is cryotherapy, as a method of inducing heat shock protein release.

Can you propose a control experiment? What will that look like? Cold, but not too cold chambers? Hot chambers?

"The study group was additionally treated with a series of 15 daily visits to a cryogenic chamber"

So, the controls should also be treated with a series of 15 daily visits to a chamber that is simply the same temperature as its surroundings.

Having 15 daily visits worth of contact with study personnel, in a chamber that exists for a specific purpose, may have a big impact, regardless of temperature. But you won't know unless you use a proper control.

Yeah, superficially-cold by say contacting metal at room-temperature.

That would add another variable and would prevent you from knowing whether the effect is due to temperature (say, a threshold effect) or the other things. I would run this control at room temperature.

Exactly; I wasn't entirely kidding - steam bath would be a reasonable control. The key (beyond providing equivalent attention from study staff) is that the intervention seems like it /might/ do something. That's why I don't think just standing in the chamber without cooling would be a suitable control.

One great challenge in studying complementary/integrative health interventions is selecting the right control group, because practitioners will argue that the control is too much like the active treatment. (So, for example, a cold shower /might/ work, if the mechanism is the same, so it wouldn't be a great control in the initial proof-of-concept experiment.)

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