On 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 whole–body 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.