MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

By guest blogger Wolfgang Denzer

Most pseudoscientific studies related to the explanation of the proposed mechanisms of homeopathy used tadpoles, wheat, or watercress as models. Results of these studies, e.g. those by Endler, Baumgartner & Co., were published in dedicated SCAM (So-Called Alternative Medicine) journals where the peers who review manuscripts have a clear tendency to support non-evidence-based studies in particular those that deal with homeopathy. In recent years several papers were published in reputable journals (see below) that purport the efficacy of ultrahigh dilution (UHD). None of these publications relates directly to homeopathy or even uses the term “homeopathy”. One thing the publications have in common is that they were either sponsored by the Russian OOO [sometimes LLC] “npf” Materia Medica Holding or co-authored by staff of that company. Materia Medica Holding produces and markets ultra-high diluted remedies that are called ‘release-active’ drugs (RA-drugs). The company founder rigorously states that their remedies are not homeopathy and that „homeopathy is doomed to have a marginal position in the modern system of therapy“. (see interview link at the end). Already a few years ago Panchin et al. (2018) analyzed several papers that involved Materia Medica Holding in one way or the other and published an article in BMJ Evidence-Based Medicine (Drug discovery today: no molecules required. http://dx.doi.org/10.1136/bmjebm-2018-111121). His remarkable conclusion was as follows: “Surprisingly, these innovative “drugs” contain no active molecules and can be considered a new brand of homeopathy. This indicates one of two possibilities: either we are at the brink of a revolution in medicine or that something went wrong with research published in numerous academic journals.” Of course, the latter assumption is correct.

The difficulty to uncover the use of an ultra-high diluted homeopathic (oops) remedy instead of proper medication published in a study is best shown by having a look at the following publication co-authored by the founder of Materia Medica Holding Oleg I. Epstein and two of his employees:

Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: results of the Russian observation retrospective program COMFORT (BMC Gastroenterol. 2020; 20: 2. Published online 2019 Dec 31. doi: 10.1186/s12876-019-1143-5).

The study deals with a retrospective analysis of the effectiveness of Kolofort, “a release-active drug” produced by Materia Medica Holding. The only statement regarding the composition of the drug reads as follows: “For the treatment of FGID [functional gastrointestinal disorders], the combination of released-active form of antibodies [RAF of Abs] to S-100 protein, TNF-α and histamine (RAF of Abs to S 100, Abs to TNF-α and Abs to H), a pathogenetically targeted drug Kolofort, was developed by the Research and Production Company Materia Medica Holding (LLC NPF” MATERIA MEDICA HOLDING”) Moscow, Russia and introduced into practical medicine. The RAF of Abs in the drug provides an anti-inflammatory, spasmolytic, and anxiolytic effect ” (notations in square brackets by me). The two following paragraphs provide information (and citations of two publications in Russian) related to the clinical trials of Kolofort. At no point in the publication are the concentrations of the active components of Kolofort mentioned! Only a web search provides further information about the composition of Kolofort (see screenshot). The three active ingredients, RAF of Abs to S-100 protein, TNF-α, and histamine, are only present at concentrations of C12, C30, and C200, respectively, i. e. they are absent. Perhaps a better notation for the remedy should be RAF in Abs of histamine, meaning release-active form in absence of histamine.

Judging from the composition of Kolofort no physiological or therapeutical reaction is to be expected. Still the authors claim that “The COMFORT program has demonstrated the positive effect of treatment [with Kolofort] in the majority of patients with IBS and FD and their combination in real clinical practice”. The authors arrived at these results by analyzing a questionnaire that had been specially developed for the assessment of gastrointestinal disorders. The questionnaire is called “7*7” [seven symptoms in seven days], but not further discussed or explained in the publication. Although there exists at least one publication from 2016 where the questionnaire was used to assess symptoms of gastrointestinal ailments (Ivashkin et al. RZHGGK. 2016;3(S):24-33. https://doi.org/10.22416/1382-4376-2016-26-3-24-33) the actual validation was not published until November 2018 (online, print June 2019) which is after the Kolofort study had already terminated (November 01, 2017, through March 30, 2018). Please note that the validation was done by one of the co-authors (V. Ivashkin) of the Kolofort study. There is certainly a good explanation for post-validating a tool used in earlier studies, but I just can’t think of one right now.

There exist several more (if not dozens) of publications by this group of authors that have already been investigated. It appears that the Materia Medica Holding director Oleg I. Epstein is heavily involved in a competition of who is capable of producing the highest number of retracted publications. Here are a few of them:

Retraction: Novel Approach to Activity Evaluation for Release-Active Forms of Anti-Interferon-Gamma Antibodies Based on Enzyme-Linked Immunoassay

The PLOS ONE Editors. Published: May 3, 2018

https://doi.org/10.1371/journal.pone.0197086

Retraction notice to “Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results” [Antiviral Research 142 (2017) 185–192]

https://doi.org/10.1016/j.antiviral.2019.02.010

Retraction notice to “Activity of ultra-low doses of antibodies to gamma-interferon against lethal influenza A(H1N1)2009 virus infection in mice” [Antiviral Research 93 (2012) 219–224]

https://doi.org/10.1016/j.antiviral.2019.02.011

Retraction Note: Release-Active Dilutions of Diclofenac Enhance Anti-inflammatory Effect of Diclofenac in Carrageenan-Induced Rat Paw Edema Model

https://doi.org/10.1007/s10753-013-9705-0

Retraction: Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice

https://www.intmedpress.com/journals/avt/article.cfm?id=3325&pid=48&sType=AVT

Retraction Note: Effects of chronic treatment with the eNOS stimulator Impaza on penis length and sexual behaviors in rats with a high baseline of sexual activity

https://www.nature.com/articles/s41443-020-0321-x

There are probably more retractions out there, but to make it onto the current Retraction Watch Leader Board (https://retractionwatch.com/the-retraction-watch-leaderboard/) a minimum of 25 retractions is required to take over rank 30. You have to work harder Dr. O. I. Epstein!

Last but not least there is an interview with Epstein available online (https://pharmaboardroom.com/interviews/interview-with-oleg-epstein-general-director-materia-medica/) where he claimed that „We proved that we [Materia Medica] are not a homeopathy company, and 1.5 years ago, the Ministry of Public Health decreed that our drugs will no longer be classified as homeopathic.“ Wow! How?

So, what does all this tell us? There exists a pool of authors, somehow connected to Materia Medica Holding, who manage to get articles, that are nothing else but homeopathy in disguise, past the peer review of reputable academic journals. It would be easy to blame the reviewers for their not soo stringent approach. But as the Kolofort paper shows, only in-depth research may actually reveal the truth. Let’s not forget, even the retracted papers made it through to publication and only a later review scrutinized their scientific merit.

It can be assumed that Materia Medica will not stop promoting their remedies through the publication of further studies. There are already publications out there that do not include any company staff as co-authors but were sponsored by the company. Judging from the rate of already retracted paper, reputation does not appear to matter. These authors possibly work along a submission-rejection-resubmission to a different journal approach until a paper gets published.

So far the homeopathy community hasn’t taken much notice of any of the beforementioned studies, most probably for two reasons: nowhere does the term “homeopathy” appear nor were the papers published in SCAM journals but rather in academic journals above the radar of homeopaths. But it can be assumed that in future, if it fits their purpose, such studies will feature among their usual dubious double blindfolded placebo trials.

Keep your eyes open for more of this stuff and please get in touch with the editorial team of the journal concerned if you discover yet another “UHD” or “RAF” publication!

11 Responses to Materia Medica Holding – The (not so) new kid on the block sponsoring homeopathy publications in disguise

  • Not called homeopathy? “A rose by any other name…..” (would not, at 30C, have any scent at all).

  • This blog is getting more depressing every day. Starting with the author: “He published nature travel books, loves reptiles and hates pseudoscience” How can you be objective if you admit that you hate an issue? As for the content, Epstein does not lie in saying that his products are not homeopathy, ironically Ernst himself goes so far as to say that if something does not follow the rules of classical homeopathy it cannot be homeopathy, but “technically homeopathic” that makes no sense as such. As for the retractions, there is no evidence of fraud in all alleged that it was because editors and post-reviewrs do not believe that something “infinitely” diluted can have a biological effect. One thing is belief and another is data, by the way, the retracted publication in PlosOne was republished in another journal of immunology. All of Epstein’s papers state that he works for Materia Medica, the complaint that they “did not declare conflict of interests” is meaningless on the part of the editors. Ernst and his team of trolls should begin to recognize that several of Hahnemann’s ideas have application outside the similia principle mainly in allopathic drugs.

  • Dear Astro.

    I suggest you focus all your efforts towards a different subject and start publishing about philosophy of science. Your approach re. objectivity towards pseudoscience will certainly shift a paradigm (or two) and you could call your theory “Astrology”. Just a reminder: pseudo comes from Greek (ψευδής, pseudes meaning “false”). Objectivity can’t change a proven falsification (unless a paradigm shift occurs).
    But more importantly: I was astonished to see your reaction to the word “pseudoscience” in a response to a homeopathy blog. Does this not imply that you accept that homeopathy is inherently pseudoscience (only in need of a little bit of tender loving care and objectivity to become science)?
    With respect to your increasingly feeling depressed by the blog I can only recommend Divaza by Materia Medica Holding. No side effects, promise!
    P.S.: I am aware that one of the retracted paper was published in a different journal. That only corroborates my assumption re. their publication approach.

    • I would take your word seriously, but in your autobiography you mention that you are a doctor of chemistry, your knowledge of philosophy of science is too crude and superficial for my taste. Retracting articles is necessary when there is evidence of fraud, not when a group of bitter and angry frustrated atheists old seniors with a title hanging on the wall don’t like paradigm shifts. I can not recommend fluoxetine to you, many side effects and the rate of bitter atheists with suicide disorders and mental disorders is quite high. Don’t be so bitter, religion is not to blame for all the misfortunes in the world.

      • ‘Tis a pleasure to read your comments in this blog. Like myself, you have to fend off dozens of cult members who seem to have a disrespect for objectivity and who have a heavy axe to grind. They forget about the power of cognitive dissonance…and their “investment” in their own worldview is to significant that anyone who questions a part of their worldview is attacked personally and with “placebo” arguments because they MUST defend their cracked paradigm.

        The fact that you know enough about the depth and breadth of homeopathic research so that their efforts to cherry-pick evidence falls apart from the mass of research that shows the biological activity and the clinical efficacy of homeopathic nanodoses.

        • I am glad you agree!
          I too found him/her amusing – but only for a while
          https://edzardernst.com/2021/08/this-is-what-it-needs-to-get-banned-from-my-blog/

        • Mr Ullman, elsewhere in this Blog you called “fools or liars” anyone who doubts that there is a difference between water and homeopathic water. For the sixth time of asking, can you please name the laboratory that can distinguish between unlabeled samples of each?
          Thank you.

        • efforts to cherry-pick evidence falls apart from the mass of research that shows the biological activity and the clinical efficacy of homeopathic nanodoses.

          Would you be able to point out, Dana, just how all this “research” has impacted on healthcare? You’ve been banging on about it for long enough. Surely science and medicine would’ve sat up and noticed by now.

          Dana. Again. The pathetic circle-jerk attempts at data-mangling and misappropriations of the scientific method employed by homeopathy freaks in their ongoing attempts to validate their fantastical beliefs in the magic powers of shaken water are completely without significance. Homeopathy has been laughed at for 200 years. It remains as pathetic as it always has been. And so do you.

  • “How can you be objective if you admit that you hate an issue?”

    I hate lies and theft and cruelty to animals and children, and meanness to other people. So I guess I’m not objective……

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