In my very first post on this blog, I proudly pronounced that this would not become one of those places where quack-busters have field-day. However, I am aware that, so far, I have not posted many complimentary things about alternative medicine. My ‘excuse’ might be that there are virtually millions of sites where this area is uncritically promoted and very few where an insider dares to express a critical view. In the interest of balance, I thus focus of critical assessments.

Yet I intend, of course, report positive news when I think it is relevant and sound. So, today I shall discuss a new trial which is impressively sound and generates some positive results:

French rheumatologists conducted a prospective, randomised, double blind, parallel group, placebo controlled  trial of avocado-soybean-unsaponifiables (ASU). This dietary supplement has complex pharmacological activities and has been used since years for osteoarthritis (OA) and other conditions. The clinical evidence has, so far, been encouraging, albeit not entirely convincing. My own review arrived at the conclusion that “the majority of rigorous trial data available to date suggest that ASU is effective for the symptomatic treatment of OA and more research seems warranted. However, the only real long-term trial yielded a largely negative result”.

For the new trial, patients with symptomatic hip OA and a minimum joint space width (JSW) of the target hip between 1 and 4 mm were randomly assigned to  three years of 300 mg/day ASU-E or placebo. The primary outcome was JSW change at year 3, measured radiographically at the narrowest point.

A total of 399 patients were randomised. Their mean baseline JSW was 2.8 mm. There was no significant difference on mean JSW loss, but there was 20% less progressors in the ASU than in the placebo group (40% vs 50%, respectively). No difference was observed in terms of clinical outcomes. Safety was excellent.

The authors concluded that 3 year treatment with ASU reduces the speed of JSW narrowing, indicating a potential structure modifying effect in hip OA. They cautioned that their results require independent confirmation and that the clinical relevance of their findings require further assessment.

I like this study, and here are just a few reasons why:

It reports a massive research effort; I think anyone who has ever attempted a 3-year RCT might agree with this view.

It is rigorous; all the major sources of bias are excluded as far as humanly possible.

It is well-reported; all the essential details are there and anyone who has the skills and funds would be able to attempt an independent replication.

The authors are cautious in their interpretation of the results.

The trial tackles an important clinical problem; OA is common and any treatment that helps without causing significant harm would be more than welcome.

It yielded findings which are positive or at least promising; contrary to what some people seem to believe, I do like good news as much as anyone else.


25 Responses to Not all alternative medicine is rubbish – encouraging news for arthritis-patients

  • Ah Prof you are a wily old fox. In the light of your previous articles and comments do I detect just a touch of cynicism? Is this a weak attempt to ‘level the playing field?’ This article reminds me of one of those compliments which is actually an insult. eg ‘Nice jersey – did your grandmother knit it for you?’

    • The title ‘Not all alternative medicine is rubbish – encouraging news for arthritis-patients’…….is a veiled form of alt med bashing which you claim is not the purpose of your blog. You say not all alt med is rubbish which implies most of it is rubbish. Just the title is alt med bashing before we even start reading the article.

      ‘I WISH THERE WERE MORE ALT MED STUDIES/RESEARCHERS OF THIS CALIBER!’……again the take home message here is that hardly any alt med studies/research of this caliber exists which obviously is not true. So yet again another form of alt med bashing….just a little more subtle. Actually not that subtle.

  • i always adored the jerseys my gran had knitted for me.

    • to tell you the truth, i have been looking for a recently published alt med article of high quality with a positive result for some time. the fact is that this was the 1st since weeks that i did find. i hope there will be more but i will not praise rubbish research simply for generating a false impression of “balance”.
      i am happy to consider other articles, in case anyone knows some – they should be new though, i.e. 2013 and i need a link to the original, e.g. to medline.


    We might extend our wishes to the medical/pharma industry research as well, just “in the interest of balance”:

    Goldacre’s intro from Bad Pharma: “Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques which are flawed by design, in such a way that they exaggerate the benefits of treatments.

    Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don’t like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug’s true effects.

    Regulators see most of the trial data, but only from early on in a drug’s life, and even then they don’t give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion.

    In their forty years of practice after leaving medical school, doctors hear about what works through ad hoc oral traditions, from sales reps, colleagues or journals. But those colleagues can be in the pay of drug companies – often undisclosed – and the journals are too. And so are the patient groups.

    And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are even owned outright by one drug company.

    Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it’s not in anyone’s financial interest to conduct any trials at all.

    These are ongoing problems, and although people have claimed to fix many of them, for the most part they have failed; so all these problems persist, but worse than ever, because now people can pretend that everything is fine after all.”

    • yes, absolutely – and if i had a blog on pharm research i would have made this point myself.

    • I, too, regard this as a significant and serious problem. However, there are quite a number of trials not conducted by the manufacturers themselves before “conventional” drugs are allowed to enter the market. So at least they show some efficacy – unlike “alternative medicine” that perscribes drugs and treatments that are entirely untested. I think this is a significant difference.
      Plus, in medicine there is a sort of loose safety net. You’ve got hospitals and doctors, you’ve got health authorities etc., so literally tens of thousands of people that at one point and time could notice if a drug does not work at all or has serious adverse effects. And they communicate with one another, at least some of the time. So at least in the case of medication for rather serious deseases on the long it is very difficult to keep a treatment on the market that just won’t do what it’s supposed to. Someone will notice and cry out. (How many drugs were banned eventually? Most of them for side effects, agreed, but certainly some for being, well, bogus, too) So actually if health authorities do prohibit a drug from being perscribed anymore, I think this is a sign that at least something in this rather flawed system works.
      In “alternative medicine” there is no such safety net, as unreliable as it may be in many cases.

      • ‘Plus, in medicine there is a sort of loose safety net.’…… seems to be a ‘very loose safety net’. Research has shown Prozac to be no more effective than placebo but with some very serious side effects like depression, suicide and violent tendencies. In fact these kind of drugs have been implicated in most of the mass shooting in the USA like Columbine. However this drug is prescribed to the tune of Billions of $$$$ worldwide even being prescribed to little children as young as two years old. Statin drugs, also netting Big Pharma, is supposed to protect patients from cardiovascular disease however in fact not only does it not impart any benefit as far as the incidence of heart attack, statin drugs have been implicated in causing cardiovascular disease by its negative effect on CoEnzymeQ10. Yes a ‘very loose net’…like Thalidomide which caused a huge amount of birth defects which supposedly had been subjected to all the ‘scientific’ tests and FDA approval. But guess what? this drug is back on the market…..just re-branded. Another example of this ‘very loose safety net’ is Vioxx which killed 60 000 people and caused untold amount of cardiovascular damage to who knows how many people. The ‘loose safety net’ eventually withdrew this drug however it was re-approved by a vote of 17 to 15… was approved by 1 vote!! This means that almost 50% of the experts voted against Vioxx being deemed safe to be prescribed to the public after 60 000 people has died. I wonder if the billions of $$$$ profit and the share price had something to do with this drug being re-approved. Yip it certainly is a ‘loose safet net’ it seems with many holes in it too.

        • Now, a source here and there would be nice as I don’t intend to conduct extensive research on all your claims. To confirm them would take hours, provided one does not accept alt-med-sites as reliable sources (and I certainly don’t). I could think of better ways to spend my time.
          At any rate, knowing pharma industries primarily serve their own purpose (or that of their owners rather) does not make alt-med any truer.
          I don’t particularly trust pharmaceutical companies. But I do trust medicine. These are two very different things, although to a certain degree one depends on the other.

          • Christoph your comments show prejudice: ‘not accept alt-med-sites as reliable sources (and I certainly don’t). I could think of better ways to spend my time’.

            It is irrelevant where the evidence is found. If the evidence is valid judging it on what website it is found just demonstrates your prejudice. Thats like saying that you would not accept that the earth is round if you read it on an alt med website.

  • Thank you for a good summary of a good trial. Unfortunately if feels like everything was well organised and done well but the result is a “so what?” We know that X-ray findings are very poor indicators of clinical symptoms. Did they look at symptoms I wonder. I think the very first trial on glucosamine was done of Xray progression of knee OA……

  • Surely, if “alternative” medicine is efficacious (i.e. not rubbish) then it is, by definition, not “alternative”. It is simply medicine.

    • in principle, this is true, i think. but, even if the finding can be independently confirmed and shown to be clinically relevant, it might take time for it to get accepted by conventional medicine. look, for instance, at St John’s Wort: we know of its efficacy for depression since many years – and how many patients get it from their GP?
      the old sayinf seems to be sadly true some times in medicine PROGRESS IS BEING MADE FUNERAL BY FUNERAL.

  • @edzard: Does St. John’s Wort translate as Johanniskraut?

  • Thanks. That is very helpful.
    I guess I won’t have to tell you how difficult to understand/translate some pretty basic terms can be in other languages. Surprisingly (or not) plant and animal names often beat me as they’re idiomatic. My intuition may have been right in this case but it’s often failed me before. So thanks again.

  • Martin, I don’t agree that “…we might extend our wishes to the medical/pharma industry research as well, just “in the interest of balance””. I think this risks setting up a false dichotomy between CAM and Con Med – that every criticism of CAM needs to be dutifully caveated with a similar criticism of Con Med (and vice versa). I think it’s entirely appropriate to debate the anti-depressant or Rosiglitazone scandals, without having to shoe-horn in some criticism of homeopathy or herbal medicine “in the interest of balance”. I don’t think this is about Con Med versus CAM, but about evidence-based medicine versus non-evidence-based medicine. After that it’s up to people/professionals to campaign as they see fit, whether it’s GPs and critical psychiatrists exposing the spurious SSRI evidence-base; endocrinologists, cardiologists and pharmacologists tackling dodgy anti-diabetic drugs; or ‘CAMologists’ subjecting CAM to rigorous critical analysis. At no point do I assume that any criticism of a CAM assumes all’s rosy in Con Med…

    • CAM or its placebo effects have crossed over to ConMed and it seems that the way we are analyzing CAM clinically at the moment is out of date. So we can not examine CAM without examining the shortfalls of medicine because it is truly has the capacity to become Complementary and help with the unwanted side effects of medicine.

      CAM exerts its effects mostly through the placebo response. It has done for millennia. The shamans and the witch doctors knew this very well and they were the early clinicians healing the body through the mind with their chants or using the nocebo effect by pointing their stick and muttering angry words at the subjects!

      The placebo effect is in the process of being studied by Con Med clinicians and has been found to have beneficial effects in neurobiology, immune system, endocrine system, cardiovascular system, motor system, etc.

      Apart from being a clinical trials methodology in medicine, the novel approach is the actual study and understanding of the placebo effect from a neurological perspective.

      One such clinician is Fabrizio Benedetti, MD, PhD, who trained both as a physician and a clinical neurobiologist, but he is also one of the world’s leading researchers on the neurobiology of placebos and the author of “Placebo Effects: Understanding the Mechanisms n Health and Disease”.

      According to Fabrizio, it is no longer feasible to study the placebo effect through the usual clinical trials because of spontaneous remissions, regression to the mean and experimentalists’ and patients’ biases. The real placebo response is a psychobiological phenomenon. The clinical trials are not a good way to study the placebo effects – because that is not their goal.

      Fabrizio also adds, “First and foremost what you have to do is to study a placebo response in a laboratory setting, not in the clinical trial setting… It is very important to stress that the clinical trial and usually the drug companies are interested in the possible difference between the new drug, the new therapy and the placebo; but they are not interested to understand why there is an improvement in the placebo group….”

      “..If you want to study the mechanism, not so much the active treatment group, but the placebo group, you have to move from the clinical trial setting to the laboratory setting… For example, if you want to perform a brain imaging study, of if you want to perform a neuropharmacological study, just to describe the biochemical pathways which are involved in the placebo effect, you have to study the patient; or otherwise study a healthy subjects in the lab… This is very, very important.”

      “The balanced placebo design is very expensive, because you need four groups of patients, not only two… The first group of patients receives placebo but told it is the active drug. The second group receives placebo, and is told it is actually the placebo; so is told the truth. The third group receives the active treatment, and it is told it is a placebo. And the fourth group receives the active treatment, but it is told it is the active treatment. The difference can be as large as 50% of the metabolic response of the brain.”

      “The balanced placebo design has very much been used in medical conditions in which the psychological component is large.”

  • Hmmm, so this is a remarkably well founded trial with a positive or promising outcome.

    Maybe I qualify for super-sceptic, but I would not subscribe to this one. It allways beats me on what poor a basis positive ratings are founded in the medical profession (both CAM and EBM). Note: I do hot have any medical education at all, I have a background in mechanical engineering and for more than 25 years I have been in charge of R&D and quality management in companies of the compressor industry. Viewing the results of the above trial with an engineering eye, I would come to a different rating:

    In the first place only one out of ten patients did have any benefit from the drug (if the drug gave any benefit at all, see below): Placebo group shows that four out of five patients would have been non-progressors anyway. ASU-group shows, five out of ten remain progressors even with the drug. So what remains is one patient out of ten, that had a benefit, the others would have blown their money up the chimney, if the had to pay for it.

    Is the result significant?
    Just assuming placebo and ASU groups were of about the same number, we have 80 non-progressors in Placebo, 100 in ASU wheras we have 120 progressors in Placebo and 99 in ASU. How to test for significance? If ASU did not give any effect at all, then the difference between the groups might be caused by assigning the patients alone. Both groups were not selected independently from each other: the second group cosists of what was left after the members of the first were taken from the totality of patients in the study. If ASU-group by chance got more non-progressors assigned than average, placebo group will be short of them by exactly the same number. If you check significance under these considerations you may apply a ‘goodness of fit’-Pearcon test – not a test for independence. So I come to a significance of p = 0.34 for the above data: the result is by far not significant. Even if the numbers assumed were a little off the mark, the gap to significance is rather big.

    For my lack of knowledge on physiology I cannot comment on the quality of the study, most of you readers will be more qualified than me. But in engineering you would not find any customer willing to pay any money for such small a chance of product improvement, being doubtful if caused by the drug at all.

    I do not subscribe to Christoph’s view either, that in the end the patients would refuse to use non working drugs and thus such drugs would be taken from the market. Placebo effect prevents that for sure.

    You wonder why I busy myself with such considerations? Well, my wife tried homeopathy after standard EBM-medicine could not help her with her maladies, not dangerous ones, just the ordinary share that a woman going on in years is about to expect, quite unpleasant though. After some time we found we had paid quite some money without any move to the better. So I wanted to know, what homeopathy is all about and began to review the evidence for homeopathy with my engineering eyes. You may guess at the findings which I will have published presently in a book. (Edzard, if this is deemed undue advertising, just erase the last nine words, please)

    • i share some of these concerns and am delighted that someone is more critical than i am.
      the thing is, it is hard to fing good trials in alt med and i has please to have identified a half decent one.

  • I appreciated very much Norbert Aust’s thoughts on the study. He has highlighted an important point in clinical trials of this type. Non-progressors or non-responders – in fact, a small population of people in whom the observed variables don’t conform to any expectation – occur in almost every clinical trial and tend to throw off the conclusions. A large enough sample size, coupled with a reasonable expectation of observation (in order to ensure strong study power), and rigorous post hoc statistical treatment of the observations are essential to separate the grain from the chaff.

    I have a slightly different problem with this study, a problem which speaks to a lot of other alt-med nostra – something to do with chemistry, or rather, biochemistry. The substance tested in this study is avocado soybean unsaponifiables (ASUs). The term ‘unsaponifiable’ tells me that these extracts are lipid-based but cannot undergo alkaline hydrolysis, presumably because these are not esters. What is the basis of standardization of these substances? How does one ensure that one batch of ‘unsaponifiables’ contain the exact same constituents as the next batch?

    ASUs seem to have been in use in clinical trials since mid-1990s. For any therapeutic agent, important considerations are, (a) the chemical composition of the substance (however complex), (b) the mechanism of action, at least the exact physiological target, (c) metabolism. Try to find solid data for these aspects of ASUs, I looked up a 2008 study (PMID 18604259), which had used in vitro and ex vivo techniques to try to answer some of these questions. They tested the hypothesis that ASU components may have anti-inflammatory and proanabolic effects on articular chondrocytes, thereby exerting a chondroprotective effect. However, they were unable to identity of the active component(s). One component of the extract that did have some of these biological effects was the phytosterol component, including beta-sitosterol.

    sterols, the major component of unsaponifiable plant material have been demonstrated to be anti-inflammatory in vitro and in animal models.

    It is hardly surprising that a sterol may have anti-inflammatory effect, regardless of the origin of the sterol. Therefore, theoretically, without going through the “ASU” extraction rigmarole, the sterol(s) could be extracted and/or synthesized and used as medicine for this purpose. Indeed, when they used beta-sitosterol as a control, they found “slightly less” but similar magnitudes of effect. They may also have dealt a blow to the ASU fanfare engaged in by the alt-med crowd when they observed:

    The similarity of activity of ASU from diverse sources when tested at equal sterol levels suggests sterols are important for biologic effects in articular chondrocytes.

    The source doesn’t matter as long as we have these sterols, then. Does it put a dent into the unholy obsession of the alt-med crowd with ‘natural’ stuff, or what?

    These authors didn’t, however, test other unsaponifiables, such as Mineral Oil or Paraffin Wax, to see if the property of unsaponifiability had anything to do with the effects. They noted that bovine chondrocytes exposed to ASU extracts or beta-sitosterol control had elevated anabolic activity, as measured by glycosaminoglycan production and collagen synthesis, and a reduction in inflammatory activities mediated by IL-1, including PGE2 synthesis.

    This still doesn’t answer the question of how the sterols (as well as the other minor components) travel from GI to the musculoskeletal joints when orally administered. Also important to know if the half-life of these components, which can give an indication for dosing.

    See, when these questions are answered, ASU will cease to remain in the exclusive domain of alt-med. I view these aspects as an important part of pharmacognosy. These are not far-fetched ideas, but ideas based on chemistry and physiology.

    Still a far cry from the madness that is homeopathy, though!

  • Where can one buy ASU-E?

  • Arthritis patients have seen huge differences when using marijuana for pain relief. It can help relief arthritis pain in finger joints and many other areas throughout the body. It’s a highly effective treatment option for patients that have arthritis that’s uncomfortable to deal with on a day-to-day basis. Great summary here on the trail and good to see some positive information!

  • Thanks for providing informative stuff….

    Actually here are many treatments available to treat arthritis, from oral medications such as over-the-counter pain killers to prescription narcotics. However, most of these only have a temporary effect. Physical therapy or any other type of active therapy helps reduce the inflammation and increase the range of motion for people suffering. Nevertheless, many sufferers look for natural remedies and holistic approaches to helping their pain.

    The nutrients and vitamins in certain foods might help to alleviate some of the pain. However, there is no concrete scientific evidence proving that any specific foods can reverse the effects or cure the pain.

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