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Ozone Therapy for Pain

A critical analysis of using trioxide to treat back pain, fibromyalgia, and arthritis

Paul Ingraham • 25m read

Ozone is a pale blue toxic gas, a variant of oxygen, its molecules each made of three oxygen atoms: “trioxygen,” rather than the dioxygen we need to survive. Ozone has a distinctive “fresh” smell and is widely used as a disinfectant — because it murders cells1 — plus many other industrial applications related to oxidation.

Ozone has also been used as a medicine for many things, including painful conditions like back pain, arthritis, and fibromyalgia — which surprised me, even though it shouldn’t have.2 It’s all classic quackery, and I will explain why in this article, with plenty of references. Ozone therapy is effectively banned by the FDA — although there is plenty of wiggle room.3

Long story short? The blog post announcing this article introduces the topic more concisely and tells the story of how I got sucked into the topic.

What’s the point? The rationale for ozone therapy

Why use ozone medically? Other than that nice fresh smell?4 Anything with the power to harm might also have the power to heal. The dose makes the poison … or the medicine.

A “seed of truth” is a standard feature of all successful quackeries, and the legitimate antibiotic powers of ozone are the seed of truth that has powered its medical reputation for one hundred and twenty years, a perennially popular snake oil — hurting and killing many people rather than curing anyone of anything, making it one of the best ever examples of popular but dangerous quackery.

Ozone therapy was particularly prominent in the era of patent medicines and peak electrical quackery, and it has a colourful history… literally.

For decades consumers could buy ozone generators for self-treatment, like this bizarre vintage medical device of unknown provenance. It still “works”: it produces a strong ozone odour & the paddle causes the sensation of little sparks when applied to the skin. Photo by neon collector Jenny Beatty, used with permission. See several more high-res photos.

The first ozone generator was invented by Nikola Tesla around 1900, and marketed as an air purifier, of all things — it is literally the opposite! The product was a desperate bid to generate some cash, which it did. It also inspired countless copycats and derivatives. The FDA started banning ozone generators of this kind in the 1950s when ozone’s toxicity and failure as a clinical disinfectant had already been clear for at least thirty years. For instance, it was tested on wounds in World War I, but killed too many human cells along with bacteria.5

Incredibly, ozone generators are still for sale as air purifiers, just as the Tesla Ozone Company intended — even leveraging Tesla’s reputation for the marketing!67 For more about ozone’s strange history, I strongly recommend this superb article from ScienceHistory.org: A Killer of a Cure: For more than a century ozone therapy has been a source of false hope for the sick and ill-gotten gains for the crooked.

Modern ozone therapy — maybe things have gotten better?

As a self-serve panacea, inhaling ozone gas was always a supremely bad idea. Just because a toxic gas was abused in the olden days doesn’t necessarily mean it is still being abused today … but it still is in this case. Ozone therapy remains strongly associated with quackery and crankery. For instance, it is a staple of many quack clinics for serious disease like cancer.

Most modern incarnations are not as dangerous and ridiculous as actually inhaling the stuff, however. As an injection, or a highly localized and controlled application of gas for some medical indications, it is probably safer and could conceivably even be efficacious in some specific ways — although there are almost certainly still some significant issues with safety and quality. Too many for sensible people!

Ozone in theory versus practice

A 2006 paper by Dr. Velio Alvaro Bocci aims to “dispel misconceptions and skepticism regarding ozone therapy,”8 and he specifically makes the case that although “orthodox” medicine has “several good reasons for refusing ozone therapy … we now have some ideas how ozone acts, how and why its toxicity can be controlled, and how therapeutic effects can be exerted.” Empowered by this knowledge, Bocci hopes the reader can start acting like a “real physician”!

Even if we embrace this view, Bocci points out the very problems with ozone therapy in the wild that make it hard to recommend to patients:

  1. Too much faith in clinical judgement (“I’ve seen it work”)9
  2. Lack of standardization, no precise ozone generator
  3. Lack of solid scientific biological and clinical data
  4. Ozone toxicity
  5. The problem of charlatans
  6. Lack of regulation and disinterest of health authorities (although it is in fact not just “regulated,” but outright banned by some agencies, like the FDA)
  7. Skeptical and uninformed scientists (and presumably science journalists like yours truly)

My mind is not closed: I can be persuaded by good evidence that ozone therapy has some potential in principle. However, actual ozone therapy in the real world is clearly far from ideal. The average health care consumer cannot identify the best providers (and the providers that advertise ozone therapy are probably the least reliable).

The “problem of charlatans” Bocci mentions is a huge problem: even if ozone therapy could be a good thing, we may never know, because charlatans have effectively made it a place where no sensible person should go. A garden cannot thrive without weeding, and some legitimate medicine has undoubtedly been strangled by quackery. If ozone therapy advocates want this tool to get validated, the best thing they can do is loudly condemn its abuses.

The first commercial ozone generators were made by Nikola Tesla — the Elon Musk of his day. His legend still powers ozone quackery to some extent well over a century later.

Ozone in dentistry

Let’s get into the evidence with a particularly prominent example of modern ozone therapy, delivered by sensible and evidence-based healthcare professionals: dentists! Dentists would never indulge in rank quackery, would they? By and large, no — despite the Atlantic article calling dentistry out, and some flouride and mercury crankery around the edges. Every field has its bad apples.

Ozone does have some uses in dentistry … as a disinfectant for hardware, not teeth.

It could conceivably be a clinical disinfectant, but the practice is not well-supported by the evidence: ozone is caustic stuff, and it is not clear that it’s worth it. The evidence is barely there.1011 And yet there is a rather vocal faction of practitioners of “ozone dentistry,” making many claims about its powers in that field.12

My personal favourite? Treating temporomandibular joint pain (or sinusitis!) by pumping ozone into the ear canal. And yet that is not the most surprising place ozone gas is pumped…

Special delivery: ozone enema, anyone?

Ozone is a toxic gas with well-established harmful effects when inhaled,1314 and encouraging people to do so for bullshit therapeutic reasons is largely a thing of the past. (Right?)

So how do you use it, then? How do you actually give it to people as medicine? Either you mechanically control what tissues are exposed to it, or you dissolve ozone into liquids which can be administered a variety of ways.

Toxic gas normally passes out of rectum, but in one amazingly popular form of ozone therapy, the gas is pumped into your butt: “rectal insufflation.” Insufflation is just jargon for “filling with gas,” so basically a gas enema. I assume that the idea is to absorb it into the bloodstream through the richly innervated mucusal lining of the rectum, like a suppository medication. Not that anyone has adequately demonstrated that this gets the ozone where it’s supposed to go, safely. Unsurprisingly, this can cause some “meteorism” — swelling of the abdomen caused by trapped gas.15

And there are other delivery mechanisms:

Promises, promises: the perpetually “promising” state of ozone therapy

Ozone therapy has many supposedly promising therapeutic applications that are controversial at best. Much like laser therapy, ozone therapy is kept alive by lots of enthusiastic and jargon-riddled speculation about how it might work (basic biological mechanisms), rather than by good clinical tests of whether or not it actually works (a common error in alternative medicine).

There is a “growing body of literature” devoted to this, of course — as there is for literally anything, thanks to a scientific publishing industry that vomits up unprecedented numbers of junky papers every year.17 Every paper is either about a low quality trial with an off-the-charts risk of bias, or a pointless garbage-in-garbage-out review of the weak trials, always padded with overheated editorializing. And what does ozone therapy supposedly have the “potential” to treat? Everything from COVID-19 and diabetes to — in the pain domain — back pain, osteoarthritis, and fibromyalgia. In papers like these, the conclusion is always “promising,” with the inevitable token disclaimer that “higher quality studies are needed” — studies that never get done.

There is no compelling clinical evidence for ozone therapy, and it remains out in medical left field … where it largely belongs, and where it will probably remain indefinitely.

Nevertheless, I will review what there is to review on fibromyalgia, arthritis, and back pain. As a science journalist (and a curious human who genuinely wants to know what works), I cannot really justify ignoring the available evidence, such as it is — even if it’s so terrible that it’s actually worse than nothing. That is the dilemma that the geyser of modern junk science has created: can’t extract much value from it, but can’t ignore it either!

The “science” of ozone therapy for fibromyalgia

There aren’t any clinical trials for this usage of ozone therapy, not even one. There is a common citation, however, widely exploited by naturopathic clinic websites: Tirelli et al describe their clinical impressions of treating sixty-five cases of fibromyalgia with ozone therapy, claiming “a significative [sic] improvement (>50% of symptoms) in 45 patients.”18 They declare it to be an “effective” therapy in their title, as if they have proven something. But this was not any kind of clinical trial; it’s just a low quality collection of anecdotal reports, put together by a group of clinicians who are clearly diehard fans of ozone therapy.

The only other example I’m aware of was an “open label pilot study”19 — more of the same, utterly worthless. This stuff barely even qualifies as junk science — it’s on a lower level than that. The only thing these citations are good for is selling ozone therapy.

The “science” of ozone therapy for arthritis

There is more science about ozone for arthritis than for fibromyalgia. It doesn’t actually add up to anything more substantive in terms of a conclusion, but there is at least a “body of literature” to pick through. There are quite a few European studies, and several of those purport to show that ozone injections improve pain, swelling, and mobility in knee osteoarthritis. However, as Sello Lebohang Manto explains in a 2020 editorial for the journal Arthroscopy:20

Dosages and volume of injections vary among studies, risk of bias is generally high, and outcomes are inconsistent and not uniformly excellent. At present, there is insufficient evidence to support the effectiveness of ozone therapy for knee osteoarthritis.

There’s clearly some skepticism there, but he’s playing softball. I would say the methods are wildly inconsistent, the risk of bias is as high as it gets,21 and the evidence may be lame but the outcomes thoroughly damn ozone therapy with faint praise — the results are technically positive, but are not impressive.

For example, Arias-Vázquez et al reviewed eight randomized “controlled” clinical trials, but only a single experiment was well controlled (by comparison with a placebo), and deemed to have a low risk of bias. They declare ozone therapy to be efficacious essentially on the strength of that one trial. Even if we could trust that one trial, it wouldn’t be enough, and it makes this meta-analysis a fine example of the trouble with so many meta-analyses: they are worse than “laws and sausages,” in that it’s horrifying to learn how most of them are made.22 And that’s the best the authors could get out of 53 studies that met initial criteria!

And what about that one study? Never trust one study, on principle, even when there are no obvious flaws, because there are countless non-obvious ways that a single study can be wrong. But there are obvious flaws here.23

Put your trust instead in the failure of dozens of junky little studies to produce a clear positive… despite their bias.24

The “science” of ozone therapy for back pain

Ozone is yet another item on the long list of things you can inject into or around the spine to treat back pain. This is the only way that ozone therapy seems to be applied to the problem of back pain (in contrast to the dizzying variety of other delivery methods for other conditions).

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Zooming out to the wide view, all such back pain treatments are probably barking up the wrong tree, at odds with decades of expertise and evidence showing that back pain is rarely caused by well-defined focal tissue trouble, and even if it was we have no way to reliably identify or treat those hot spots. This is why all kinds of treatments for back pain mostly fail, which is all explained thoroughly in the (free) introduction to my back pain book.

But for the sake argument: what if the problem really is a damaged and sore disc, and we could confirm that? We know this scenario doesn’t explain most cases, but it certainly explains some. What magic substance can heal that injured tissue? There is no such substance!

Most allegedly regenerative treatments, like platelet-rich plasma, are just modern snake oil. The best that regenerative medicine has to offer so far is probably autologous chondrocyte implantation — implanting a “patch” of your own cartilage cells in your knee — and that’s highly technical and specific, and not just an injection.

Can ozone do better? What are the odds? When we already know that it does precisely nothing for simpler problems than back pain, like ordinary knee arthritis?25 If ozone can’t help knee arthritis, it doesn’t seem likely to help troubled spinal tissues either.

Are there any other relatively simple pathological models? The only obvious choice is tendinopathy. If there were three good trials showing better than modest benefit for that, I would consider them a cause for optimism for the same treatment in the back. Instead, there is just one feeble one, clearly positive and intriguing, but just not good enough.26

So the basic idea is that spinal tissues that are irritated or injured can somehow be calmed or healed by ozone… which is definitely not known to occur with simpler problems. But the biological details are irrelevant if it doesn’t work, so does it work? Is it safe, and can a meaningful benefit be measured? That’s all that matters, and the only way to find out is with well-designed clinical trials (conducted by people who aren’t just trying to prove that ozone therapy works).

That science does not exist. Therefore, we simply don’t know if ozone works for back pain.

There are a couple dozen candidates, all of them “positive” studies. This is not a win. Anyone can look up ozone therapy on PubMed and find trials that say injected ozone helps back pain, but it takes a seasoned science journalist and skeptic to know that it’s all junk science. That is the only story here — not what the science says, but that the science is so sketchy that it might as well not exist.

Even ozone proponents know it’s a mess. Scientific reviews — written by the usual European suspects, the Italian and Spanish fans of ozone therapy — clearly state that the studies have “overall poor methodologic quality, with most studies flawed by relevant bias”27 But that doesn’t prevent those reviewers from delivering a good-news conclusion in the next sentence! They think ozone therapy is “proven” — proven! — “to be a safe treatment with beneficial effects in pain control and functional recovery,” based on studies that are “poor” and mostly “flawed by relevant bias”!

Proof is a high bar. It’s irresponsible nonsense to speak of safety and benefits being “proved” by blatantly shoddy research. Every introduction to every paper on the topic reads like it was produced by an ozone therapy marketing board. The red flags for pseudoscience are thick.

In the absence of good trial data, we must fall back on other factors, on the scientific context: data from similar conditions (arthritis, tendinitis), scientific plausibility, safety, and practical matters like cost, accessibility, and our ability to identify competent providers. And ozone does not do well by these measures.

I can concede a remote possibility that injected ozone is in fact useful for some patients, but only in principle. In practice, it’s a blatantly unproven injection, and all injections (of anything, for any reason) are “invasive” and somewhat risky, and there are some additional risks with injecting ozone — a toxic substance, administered by many clinicians who are such obvious cranks that we cannot begin to trust their competence. Or maybe they are not so obvious, which is probably worse!

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Ozone therapy is a near perfect example of pseudoscience

Vintage quackery is quaint, but modern quackery is evil, and it’s clear that ozone therapy is a •chef’s kiss• example of dangerous medical pseudoscience:

About Paul Ingraham

Headshot of Paul Ingraham, short hair, neat beard, suit jacket.

I am a science writer in Vancouver, Canada. I was a Registered Massage Therapist for a decade and the assistant editor of ScienceBasedMedicine.org for several years. I’ve had many injuries as a runner and ultimate player, and I’ve been a chronic pain patient myself since 2015. Full bio. See you on Facebook or Twitter., or subscribe:

What’s new in this article?

Jan 7, 2022 — Improved the back pain section significantly. My first version was a little too ranty and dismissive. It is now more thoughtful and thorough and looks a little closer at the rationale. Still ranty! But the ranting is now a sauce instead of the main dish. Also, I paywalled the back pain section — the first example of a small members-only section, just one key piece of an article reserved for members, and also available in a book.

January — Added a section about injected ozone for back pain. Also made a number of minor editorial corrections, added a couple images, and brief mentions of veterinary uses of ozone, and vaginal insufflation of ozone. The article is now “ready for prime time.”

2021 — Publication.

Notes

  1. Ozone is an “antibiotic” in the general sense that is it is against life. All oxygen is an oxidant, meaning that it strips the electrons from other compounds, and trioxygen is a much more powerful oxidizer than dioxygen. Ozone “corrodes” cellular membranes efficiently, damaging tissues at concentrations greater than about 0.1 parts per million.
  2. These conditions are the “big three” common, difficult pain problems. Hundreds of millions of people around the world are suffering from them at any given time, if not more. They are an ideal market for cures. And so these conditions are dumping grounds for every conceivable kind of treatment and therapy.
  3. Code of Federal Regulations Title 21 Sec. 801.415 Maximum acceptable level of ozone (FDA Website).

    In 2006, the FDA prohibited ozone therapy “in any medical condition for which there is no proof of safety and effectiveness,” and there’s your wiggle room — “proof” can be debated ad nauseum.

    For medical devices (like the equipment that generates ozone), the FDA is primarily focused on safety, not efficacy, but officially requires “valid scientific evidence that there is a reasonable assurance that the devices are safe and effective for their intended uses.” Their position is clear:

    “Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in a concentration far greater than that which can be safely tolerated by man and animals.”

  4. Which probably has a lot to do with it, actually. For instance, it almost certainly was the basis for all applications as an “air freshener,” which is how ozone therapy got its start in the world (more on this momentarily). Most quackery, for all its scientific pretensions, usually owes its successes to extremely simple, pleasing sensory experiences and simplistic reassurances. For instance, where would chiropractic be without the genuine sensory pleasure of a spinal “pop,” paired with the comforting fairy tale of putting a “spine back in line”? See The Chiropractic Controversies.
  5. Stoker G (1916). “The Surgical Uses of Ozone.” Lancet. 188 (4860): 712.
  6. Here’s a mold decontamination company fawning over Tesla and singing the praises of his invention: Ozone Generators: Yet Another Revolutionary Invention by Nikola Tesla. 🤮
  7. United States Environmental Protection Agency. “Ozone Generators that are Sold as Air Cleaners.” Internet. Accessed 2021-12-29.

    The FDA reports that “there are many brands and models of ozone generators on the market. They vary in the amount of ozone they can produce. In many circumstances, the use of an ozone generator may not result in ozone concentrations that exceed public health standards. But many factors affect the indoor concentration of ozone so that under some conditions ozone concentrations may exceed public health standards. … The actual concentration of ozone produced by an ozone generator depends on many factors.”

    The completely unsurprising bottom line:

    Available scientific evidence shows that, at concentrations that do not exceed public health standards, ozone is generally ineffective in controlling indoor air pollution.

  8. Bocci VA. Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res. 2006 May;37(4):425–35. PubMed #16624639 ❐
  9. Bocci specifically says, “excessive empiricism.” However, for a guy who acknowledges that excessive empiricism is a problem, he sure does rely on it:

    “Our many treated patients answer for me and they loudly say that it is very beneficial. The compliance is excellent and the patients, as soon as the therapeutic effect declines, ask for a new cycle. This is an excellent proof…”

    Is it, though? No, it’s not. That’s highly fallible observation, AKA “anecdotal evidence.” Never forget:

    The three most dangerous words in medicine: in my experience.

    Mark Crislip, MD

  10. Santos GM, Pacheco RL, Bussadori SK, et al. Effectiveness and Safety of Ozone Therapy in Dental Caries Treatment: Systematic Review and Meta-analysis. J Evid Based Dent Pract. 2020 12;20(4):101472. PubMed #33303100 ❐ This is a review of 12 randomized controlled trials, all of low quality, comparing ozone therapy to placebos and other conventional methods of treating dental caries. Those trials did not produce enough good quality evidence to be informative: “there is not enough support from published RCTs to recommend the use of ozone for the treatment of dental caries.”
  11. Kist S, Kollmuss M, Jung J, et al. Comparison of ozone gas and sodium hypochlorite/chlorhexidine two-visit disinfection protocols in treating apical periodontitis: a randomized controlled clinical trial. Clin Oral Investig. 2017 May;21(4):995–1005. PubMed #27173580 ❐ Of the many citations I could have chosen, I thought this one was particularly useful because it is about a particularly classic application of ozone to a uniquely dental challenge — basically, trying to kill off bacteria causing inflammation of the tip of tooth’s root after a root canal. It’s a well-designed simple head-to-head trial of ozone versus conventional techniques… and there was no difference at all. If ozone therapy can’t perform better than that in a test like this, it’s unlikely to be important for anything else in dentistry.
  12. Domb WC. Ozone therapy in dentistry. A brief review for physicians. Interv Neuroradiol. 2014 Oct;20(5):632–6. PubMed #25363268 ❐ PainSci #52014 ❐ This paper is by one of the most prominent champions of ozone dentistry, and contains examples of many dental applications, none of which are actually evidence-based: wound healing, dental caries, oral lichen planus, gingivitis and periodontitis, halitosis, osteonecrosis of the jaw, post-surgical pain, plaque and biofilms, root canals, dentin hypersensitivity, temporomandibular joint disorders … and even teeth whitening.
  13. Broeckaert F, Arsalane K, Hermans C, et al. Lung epithelial damage at low concentrations of ambient ozone. Lancet. 1999 Mar;353(9156):900–1. PubMed #10093991 ❐
  14. Bell ML, McDermott A, Zeger SL, Samet JM, Dominici F. Ozone and short-term mortality in 95 US urban communities, 1987-2000. JAMA. 2004 Nov;292(19):2372–8. PubMed #15547165 ❐ PainSci #52186 ❐
  15. Hidalgo-Tallón J, Menéndez-Cepero S, Vilchez JS, Rodríguez-López CM, Calandre EP. Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study. J Altern Complement Med. 2013 Mar;19(3):238–42. PubMed #23046293 ❐ “Transient meteorism after ozone therapy sessions was the most frequently reported side-effect.”
  16. Specifically hemoperfusion, which a cousin to dialysis. You can see an example of this process being promoted by a dentist here. The term “dialysis” (with scare quotes) is probably used for “clarity” because it will make more “sense” to people — and it probably is a reasonable oversimplification… of a ridiculous thing. This is for dentistry! This would be a reach in any medical context, but dentistry?! Just a little bit beyond dental scope of practice. Where by “a little bit” I mean a lot.
  17. There has always been a full range of quality in scientific papers, and even legitimate science is often incomplete and weak. However, the lower end has surged grotesquely since the 1990s. There is now an industry — a huge industry — of both junky and actually fraudulent journals (Beall, Gasparyan). “Predatory journals” (numbering in the thousands) exist only to take money from gullible and/or desperate academics who must “publish or perish.” These so-called journals collectively publish millions of papers annually with “no or trivial peer review, no obvious quality control, and no editorial board oversight” (Sax).

    And so these days it is now easy to find “support” for “promising” evidence of basically anything — and no one will know the difference unless they know how to check. There is a full discussion of this problem in my article, 13 Kinds of Bogus Citations.

  18. Tirelli U, Cirrito C, Pavanello M, et al. Ozone therapy in 65 patients with fibromyalgia: an effective therapy. Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1786–1788. PubMed #30840304 ❐
  19. Hidalgo-Tallón 2013, op. cit.
  20. Manoto SL. Editorial Commentary: Is Medical Ozone Therapy Beneficial in the Treatment of Knee Osteoarthritis? Arthroscopy. 2020 01;36(1):287–288. PubMed #31864590 ❐
  21. I don’t actually think research needs to be dispassionate and objective, though it’s a fine goal to shoot for. Bias inspires research as much as it corrupts it. But I get concerned when I see a lot of bias combined with a lot of weak methodology and exaggerated clinical significance. Punctuating the bias here, much of this research comes from the same people — Italy especially seems to be a hotbed of ozone therapy — and they are also busy writing systematic reviews of their own low-quality studies, with predictably optimistic conclusions and the inevitable calls for more and better research (to confirm what they obviously already believe).
  22. Ioannidis JP. The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta-analyses. Milbank Q. 2016 09;94(3):485–514. PubMed #27620683 ❐ PainSci #53217 ❐ “The production of systematic reviews and meta-analyses has reached epidemic proportions. Possibly, the large majority of produced systematic reviews and meta-analyses are unnecessary, misleading, and/or conflicted.”
  23. Lopes de Jesus CC, Dos Santos FC, de Jesus LM, et al. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study. PLoS One. 2017;12(7):e0179185. PubMed #28738079 ❐ PainSci #52013 ❐

    The risk of bias is declared loudly and clearly in the introduction when authors explain that oxygen therapy works by “activating the cellular metabolism” and “making the redox system function properly,” which is idiotic. These are the rationalizations of true believers out to prove a pet theory, not good medical scientists. They complain about the failure of “allopathic” medicine to treat arthritis, which is a huge red flag for bias (the term “allopath” is used only by alt-med ideologues, and always disparagingly). More substantively, they also declare the statistical “significance” of their results without acknowledging low effect sizes, which is a major foul. The actual effect size reported was not “marked” but modest … even after all the p-hacking they almost certainly did, consciously or unconsciously.

    I’m not saying that the results are necessarily wrong because there’s a stink of bias on them, only that there are obvious reasons why we definitely do not trust this single study.

  24. Not all “absence of evidence” is equal. A true absence of evidence is uninterpretable, and in that case we must embrace our ignorance. Instead we often we see an absence of good evidence, and we can extract a meaningful signal from the sloppy stuff. A bunch of junky little studies of a bogus therapy, with a high risk of bias, will produce false positives (as they clearly do for some of the classic snake oils like homeopathy and acupuncture). In this case, they don’t even achieve that!
  25. Manoto 2020, op. cit. Manoto is the best single citation for “ozone therapy isn’t evidence-based medicine for knee arthritis,” but the situation is clearly even worse than Manoto concluded. See my full analysis above for how the cruddy science backfires: “Put your trust instead in the failure of dozens of junky little studies to produce a clear positive… despite their bias.”
  26. Ulusoy GR, Bilge A, Öztürk Ö. Comparison of corticosteroid injection and ozone injection for relief of pain in chronic lateral epicondylitis. Acta Orthop Belg. 2019 Sep;85(3):317–324. PubMed #31677627 ❐ A comparative study (not randomized or well-controlled), reporting “better” results from ozone than steroid injection. Looking into the details, it is an extremely rare example of an abstract that is vague about effect size … that was actually impressive. It is an unambiguously positive result for ozone, but from a single trial of a type that we cannot take to the bank. Unfortunately, the only thing such a study is good for is justifying a better study.
  27. Sconza C, Leonardi G, Kon E, et al. Oxygen-ozone therapy for the treatment of low back pain: a systematic review of randomized controlled trials. Eur Rev Med Pharmacol Sci. 2021 Oct;25(19):6034–6046. PubMed #34661263 ❐

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