Mar 15 2016

Cryotherapy – Basic vs Clinical Science

RoganOn a recent episode of the Joe Rogan Experience (starting at the 2:10 mark), Rogan discusses an article I wrote previously on Science-Based Medicine about whole body cryotherapy (WBC). Rogan did not like my article, which he characterized as “poorly done and poorly researched.” He was discussing the article and WBC in general with his guest, Dr. Rhonda Patrick.

What this discussion revealed, in my opinion, is a significant lack of understanding of the roles of basic science research vs clinical research. Before I get to the discussion, here is a quick review of WBC.

Whole Body Cryotherapy

WBC involves exposing the whole body to extremely low temperatures, -200 to -240 degree F temperatures (-125 to -150 C) for 1.5-3 minutes. There are chambers where the head sticks out the top, and there are chambers that you step into entirely.

WBC is offered as a spa treatment, and not surprisingly there are a range of health claims made for the treatment, including the usual “detox,” “supports the immune system,” and “anti-inflammatory” effects. Specific claims are made for arthritis, exercise recovery, recovery from injury, and at the extreme end even curing serious diseases like cancer.

From a basic science perspective, a lot of interesting things happen when you stress the body by exposing it to extreme low temperatures. Histamine levels are decreased, norepinephrine is increased, TNFalpa activity is decreased, etc. It is therefore plausible that a biological effect from WBC can be exploited for clinical benefit. Effects seem to favor an anti-inflammatory effect, so application to inflammatory conditions is especially plausible.

This is now where the clinical evidence comes in. Knowing the physiological effects are not enough. The body is complex and it is extremely difficult to tease out all of the downstream effects from any intervention sufficient to predict net clinical effects. We always will still need clinical studies to determine clinical effects.

Questions that need to be addressed clinically are – for each specific indication, what is the net clinical effect, what is the magnitude of this effect, what is its duration, what are the side effects and compensatory effects, and how do various interventions compare? With this information we establish a net risk vs benefit for specific clinical applications compared to the risk vs benefit of other treatment options.

With regard to WBC the clinical evidence overall is preliminary. We lack rigorous definitive evidence. With regard specifically to recovery of muscle soreness, a 2015 Cochrane systematic review concluded:

There is insufficient evidence to determine whether wholebody cryotherapy (WBC) reduces self-reported muscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

A 2016 update concluded.

In summary, the body of evidence in this review does not support the hypothesis that whole body cryotherapy effectively reduces muscles soreness and or improves subjective recovery, after exercise in physically active young men. There is no evidence on its use in women or elite athletes. It’s also important to note that the lack of evidence on adverse events means that one cannot be confident that this exposure to extreme cold air in either the short or long term is without potential harms.

The updated review was a bit more negative in tone.

For arthritis, a 2014 systematic review found:

Cryotherapy should be included in RA therapeutic strategies as an adjunct therapy, with potential corticosteroid and nonsteroidal anti-inflammatory drug dose-sparing effects. However, techniques and protocols should be more precisely defined in randomized controlled trials with stronger methodology.

There were six studies included, with generally weak methodology. What evidence we have is encouraging for subjective reduction in pain, but more rigorous trials are needed.

A 2015 study, published after the above review, compared WBC to traditional rehabilitation (TR) and found:

After therapy both groups exhibited similar improvement in pain, disease activity, fatigue, time of walking, and the number of steps over a distance of 50 m. Only significantly better results were observed in HAQ in TR group (p < 0.05). However, similar significant reduction in IL-6 and TNF-α level was observed. The results showed positive effects of a 2-week rehabilitation program for patients with RA regardless of the kind of the applied physical procedure.

A 2015 study on the use of WBC in chronic lower back pain had a double-blind placebo-controlled design, comparing WBC at -67C to sham cryotherapy at -5C. The study found:

Cryochamber therapy with -67 °C is not superior to (sham cryo chamber) with -5 °C.

I also found two studies looking at muscle function in ankylosing spondylitis showing positive effects, but these were small and unblinded studies. There was one study showing benefit for fatigue in MS patients.

Those of you familiar with science-based medicine and my articles here will recognize this pattern of evidence – there are promising basic science clues, but the clinical evidence is preliminary and mixed (small numbers total without rigorous controls), and as studies evolve to more rigorous and controlled designs the clinical effects tend to disappear. Meanwhile the popular claims being made are way beyond what is clinically proven.

At the present time I would characterize the overall clinical evidence for WBC for any indication as being preliminary, in some cases promising, but overall mixed. There is insufficient clinical evidence to conclude that WBC is safe and effective for any specific indication. Larger and more rigorous studies are needed, and specifically we need to compare WBC to less dramatic treatments, such as higher temperatures, local application, cold water exposure, and just traditional treatment methods.

The Rogan-Patrick Discussion

Rogan and Patrick did not agree with my conclusions, but they could not really contradict them because the evidence is the evidence. I cited the most recent systematic reviews of the clinical evidence, with any subsequent relevant studies.

Rogan simply stated I did not do sufficient research, which usually means, “he didn’t cherry pick the studies I wanted him to.” It might mean, “he didn’t base clinical claims on basic science research like I do.” He also offered anecdotal evidence.

Dr. Patrick focused on the basic science research, which is fine by itself. However, she made the classic mistake of failing to appreciate the limits of extrapolating from basic science research and the need for clinical research to address specific clinical claims.

In addition to anecdotes and basic science, she also offered rationalizations for why the clinical research has poor methodological rigor. She specifically said, how can you blind subjects to exposure to extreme cold?

Well, I referenced a study above that did just that. You can expose subjects to sham cryotherapy with cold temperatures, but not as cold as is typically used in WBC. At the very least that study suggests that we may not need to use extreme low temperatures, -5C is enough (of course, this also needs further study).

You can, in essence, look for a dose-response effect. You can expose subjects to varying temperatures for varying amounts of time and for varying numbers of treatments.

Dr. Patrick also offered as an explanation the claim that some scientists are just “closed minded” – yes, she played the tired, old “closed minded” card. Some scientists are just stuck in a loop of debunking, she feels. I guess you need to have an open mind (read “credulous”) to break out of that “dangerous” cycle.

This response – appeal to anecdotes, extrapolation from basic science, special pleading for lack of rigor, and appeal to “open mindedness” – is so predictable it is sad. You could insert any treatment in which the clinical evidence is insufficient to support the claims made and you will find the exact same set of rationalizations.

We know from extensive experience and a large and growing body of research looking at published scientific data itself that claims based on anecdotes, basic science, and preliminary or weak clinical evidence alone have a very poor track record of panning out when rigorous definitive clinical trials are ultimately done (most such claims will prove to be wrong).

Keep in mind, I am not saying that WBC cannot work (it’s not homeopathy), or even that it does not work. I am not “poo pooing” or “dismissing” WBC as Rogan seems to think. What I am doing is consistently applying a very carefully thought out and well-researched standard of clinical evidence to all clinical claims (a standard that I coined the term “science-based medicine” to represent).

Rogan and Patrick were unable to counter my assessment of the clinical evidence. They were unable to present clinical evidence I neglected. Instead they essentially argued for a lowering of the standard (sound familiar?), including the four strategies I listed above.

If they are going to legitimately disagree with where I set the threshold for reasonable clinical evidence, then they have to make that case, which they failed to do (and barely even addressed). I’m not saying they have to read the over 3,000 articles we have collectively published here and at SBM, that would not be fair. But they should have at least a minimal familiarity with our position.

They could start by reading:

Evidence Thresholds

Registering Studies Reduces Positive Outcomes

About SBM

I am always willing to have a conversation about the nature of clinical evidence, how to properly evaluate it, and how we know if a treatment is truly effective. Understanding patterns in the clinical research is complex, and I don’t expect non-experts to understand all the nuances. I do expect, however, that if they wish to express a public opinion on the matter they will fairly engage with the issue and not resort to long-countered fallacious arguments.

14 responses so far

14 Responses to “Cryotherapy – Basic vs Clinical Science”

  1. steve12on 15 Mar 2016 at 10:48 am

    But my Aunt did it and she felt great afterward. That’s at least the equal of a recently updated Cochrane review….

    It is funny that the very same people who advocate for treating the “whole” person and not just specific diseases or symptoms also want to assume that a given targeted basic finding (lowered TNFa activity) is sufficient evidence for clinical treatment without looking at the effect on the “whole” person.

    The only consistent finding I see in all of the various forms of BS (other than religion) I see is this: if the establishment (however one defines this) is for it I’m against, it and vice-versa. CAM , conspiracy theorists, free energy nuts, UFO nuts, flat-Earthers, on and on.

  2. Kestrelon 15 Mar 2016 at 11:01 am

    I hope this escalates to either Steve appearing on Rogan’s show, or Steve guest-announcing UFC next to Rogan.

  3. steve12on 15 Mar 2016 at 11:09 am

    “I hope this escalates to either Steve appearing on Rogan’s show, or Steve guest-announcing UFC next to Rogan.”

    Not UFC guy, but I’m not sure which one I’d like to see more…

  4. Steven Novellaon 15 Mar 2016 at 11:47 am

    I have reached out to Joe Rogan, who declined to have me on his show. I just invited him to appear on the SGU to discuss this and his response was, “No thanks.”

    Interpret that as you will.

  5. DevoutCatalyston 15 Mar 2016 at 12:43 pm

    I interpret it to mean he doesn’t want a tenacious skeptic provoking cognitive dissonance on his show.

    Michael Shermer was on The Joe Rogan Experience recently, did pretty well, but did not challenge him on every point, for example:

    Rogan: “I don’t mind raw milk, raw milk I like, it’s just…I felt like homogenized and pasteurized milk — once you do that — I mean it’s great as far as you could store it in a store and it lasts for a long time, but you’re cooking out all the enzymes…”

    Shermer: “Right”

    Rogan: “…it’s just not the best thing for your body”

    Shermer: “Yep”

  6. Willyon 15 Mar 2016 at 2:49 pm

    About a year ago, I discovered Rogan’s podcast. I listened to two episodes and haven’t listened to him since. He was a loud mouth, obnoxious, and unnecessarily vulgar. He was absent interesting thoughts. I forget the topics he covered, but I remember thinking he wasn’t especially insightful. In retrospect, he seems a lot like Trump.

    I’m not one who would like to see him on the SGU.

  7. Paul Danger Kileon 15 Mar 2016 at 3:56 pm

    At this point, because of advertising, to non-physicians, the words “clinically proven” mean, “we got someone somewhere to sell this to their patients.” I understand why you are making the distinction, but it’s probably enough to say that there is no scientific evidence for specific therapeutic effects.

  8. steve12on 15 Mar 2016 at 5:06 pm

    Paul:

    “…there is no scientific evidence for specific therapeutic effects.”

    There actually is some scientific evidence, but that evidence is of a basic rather than clinical nature. They’re missing that distinction.

    Great name by the way….

  9. steve12on 15 Mar 2016 at 5:06 pm

    As I read it what you said means the same thing….

    Adventures in pedantry.

  10. Robneyon 15 Mar 2016 at 6:23 pm

    Hi Steve,

    I’m a big fan of both the SGU and the Joe Rogan Experience and I’d love to see you on Rogan’s show.
    I think his long-form conversational style would work well for you.

    Rogan is fairly open minded and has a general respect for the scientific process but I don’t think he is particularly sceptical in his thinking. He has a history of hosting pseudoscientists on his show and sometimes promotes obvious pseudoscience himself (he’s a sucker for the naturalistic fallacy). I think some of the supplements he promotes (and might have a business interest in) are of dubious merit.

    It’s disappointing he declined your request. He had Michael Shermer on recently and often has people on with whom he disagrees. so I’m not sure why he wouldn’t want to talk to you.

    I think a lot of people out there would like to see you on his show. He has a big audience and it would be a good way of promoting scepticism. Maybe Cara could have a word with him, I believe she is friends with him.

  11. Davdoodleson 16 Mar 2016 at 1:51 am

    I’ve read and re-read Dr N’s original article and I seriously can’t see their problem with it. Basically, Dr is is critical of over-hyped claims about WBC, because the evidence doesn’t support those claims. That’s it. Hardly a complex or controversial thing to say.

    But, for whatever reason, they either didn’t understand that sensible conclusion, or they reject it despite the evidence. Strange, given they both seem to be reasonably intelligent and thoughtful people.

    They seemed to shift very quickly from an un-supported claim that “Novella’s article was poorly researched” into a long list of “this chemical goes up and that one goes down” basic science stuff, and a lot of “I like it and this other guy likes it and these guys feel good after it” and whatnot. Based on that, my guess is that theirs was really just a knee-jerk reaction to something they like being critisised. Pretty common behaviour in humans…

  12. ccbowerson 16 Mar 2016 at 9:15 am

    Davdoodles

    Here’s what seems to happen quite often and explains a lot of disagreements in politics and elsewhere- People tend to see themselves as reasonable people (regardless of whether they are being so at the time), and when people strong attachments to ideas (often ideological commitments or emotional investments) at one end of a spectrum, they tend to perceive people who have a moderate balance view as being biased towards the other side. In other words, people tend to take their perspective as the moderate or reasonable one, and view other perspectives as biased to the extent that they diverge from their own. Our own perspectives tend to anchor our assessment of what is reasonable, so other perspectives sound unreasonable before we even start looking at their arguments.

  13. Newcoasteron 16 Mar 2016 at 12:27 pm

    @Devout Catalyst

    Disappointing Shermer gave Rogan a pass on his raw milk BS, but I assume he was there to discuss some other topic, and didn’t want to get that conversation sidetracked. I believe Rogan is a Libertarian, so likely had some common ground with Shermer there as well.

    I’ve never listened to his show, I just vaguely remember him as a bad actor from a 90’s sitcom about a radio station, and then he was host of that awful reality show where people debased themselves for money performing dangerous or disgusting stunts. (Ok, that describes most reality shows I guess. )

  14. hammyrexon 21 Mar 2016 at 12:53 pm

    I’m surprised somewhat that this topic and the SGU discussion didn’t talk about the big pink elephant in the room – Rogan has a financial relationship with Cryohealthcare and many of the gyms he has an ownership stake in offer cryotherapy. Then again, not going that avenue may have been conscious as I’m sure defenders would have incorrectly viewed it as poisoning the well instead if shining a light on a legitimate conflict of interest.

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