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

research

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The global market for dietary supplements has grown continuously during the past years. In 2019, it amounted to around US$ 353 billion. The pandemic led to a further significant boost in sales. Evidently, many consumers listened to the sly promotion by the supplement industry. Thus they began to be convinced that supplements might stimulate their immune system and thus protect them against COVID-19 infections.

During the pre-pandemic years, the US sales figures had typically increased by about 5% year on year. In 2020, the increase amounted to a staggering 44 % (US$435 million) during the six weeks preceding April 5th, 2020 relative to the same period in 2019. The demand for multivitamins in the US reached a peak in March 2020 when sales figures had risen by 51.2 %. Total sales of vitamins and other supplements amounted to almost 120 million units for that period alone. In the UK, vitamin sales increased by 63 % and, in France, sales grew by around 40–60 % in March 2020 compared to the same period of the previous year.

Vis a vis such impressive sales figures, one should ask whether dietary supplements really do produce the benefit that consumers hope for. More precisely, is there any sound evidence that these supplements protect us from getting infected by COVID-19? In an attempt to answer this question, I conducted several Medline searches. Here are the conclusions of the relevant clinical trials and systematic reviews that I thus found:

Confused?

Me too!

Does the evidence justify the boom in sales of dietary supplements?

More specifically, is there good evidence that the products the US supplement industry is selling protect us against COVID-19 infections?

No, I don’t think so.

So, what precisely is behind the recent sales boom?

It surely is the claim that supplements protect us from Covid-19 which is being promoted in many different ways by the industry. In other words, we are being taken for a (very expensive) ride.

I was alerted to this announcement by the Faculty of Homeopathy:

Faculty of Homeopathy Accredited Education

The role of Dentistry in Integrative Medicine and Homeopathy

Dentistry appears to be the Cinderella of healthcare and the importance of good oral health is hugely underestimated. The mouth is the portal into the rest of our bodies. There is increasing evidence proving that health of the oral cavity has strong links with the health of the rest of the body especially increasing risk of heart disease, low birth weight babies and type 2 diabetes. The aim of this webinar is to highlight the vital importance of dentistry and oral health in integrative medicine and why healthcare professionals need to work closely with dentists. It will also cover how, as homeopaths, we can appreciate symptoms in the mouth as indications of general health or disease and manage dental conditions.

THE TICKETS FOR THIS WEBINAR ARE LIMITED THEREFORE, PLEASE REGISTER NOW TO ENSURE ACCESS.

Some splendid platitudes there:

  • the Cinderella of healthcare
  • The mouth is the portal into the rest of our bodies
  • health of the oral cavity has strong links with the health of the rest of the body…

But what about the importance of dentistry in integrative medicine? The importance of dentistry in medicine is fairly clear to me. However, what is the importance of dentistry in integrative medicine?

Even more puzzling seems the ‘role of dentistry in homeopathy’? What on earth do they mean by that? Perhaps they meant the ‘role of homeopathy in dentistry’?

And what is the role of homeopathy in dentistry? The British Homeopathic Dental Association should know, shouldn’t they? On their website, they explain that they are a group of dentists and dental care professionals that have an interest in using homeopathy alongside our dentistry.

On the basis of what evidence, you ask? They kindly provide an answer to that question:

In dentistry there is limited research though studies have shown improved bone healing around implants with Symphytum and reduced discomfort and improved healing time with ulcers and beneficial in oral lichen planus. These studies have small numbers and are not generally acepted as stong evidence.

Are they trying to tell us that there is no good evidence? Looks like it, doesn’t it? In this case, the above Webinar seems rather superfluous.

For those of you who want to save the money for the tickets, here is a full and evidence-based summary of all the conditions where homeopathy might be helpful in dentistry:

THE END

 

Research on glucosamine, one of the most popular dietary supplements, shows anti-inflammatory and anti-cancer benefits with minimal adverse effects. An international team of researchers aimed to explore the relationship between the use of glucosamine and the risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study.

Participants were enrolled between the years 2006 and 2010 and followed up to 2020. The Cox proportion hazards model was used to assess the relationship between glucosamine use and the risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings.

A total of 439,393 participants (mean age: 56 years; 53% females) with a mean follow-up of 11 years were included for analyses. There were 82,603 (18.80%) participants reporting regular use of glucosamine at baseline. During follow-up, there were 1,971 (0.45%) lung cancer events documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio=0.84, 95% CI: 0.75-0.92, p<0.001) and lung cancer mortality (hazard ratio=0.88, 95% CI: 0.81-0.96, p=0.002) in fully adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared to those without a family history.

The authors concluded that regular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.

A previous analysis of the same data concluded that regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases. The new analysis shows a strong association with lung cancer.

This is certainly interesting, but does it prove a causal relationship?

The answer is no.

Correlation is not causation!

What would be helpful in testing whether we are dealing with a cause-effect relationship?

  1. We need data from other studies. Several other epidemiological investigations indicated that glucosamine use might play a role in the prevention of cancer.
  2. We require to know the strength of the association. The new analysis suggests that it is indeed strong.
  3. We need a mode of action. Might the anti-inflammatory action of glucosamine explain the effect?
  4. We should ask whether there is a dose-response relationship. As far as I know, this has not been addressed as yet.
  5. Ideally, we would require a randomized trial to test the hypothesis. But I fear that such a study might be too difficult to conduct and will thus not be forthcoming.

And what if glucosamine should one day be proven to reduce the cancer risk? Would it become the first ALTERNATIVE measure to prevent cancer?

Certainly not!

It would automatically become a conventional method of cancer prevention. All the research into the subject has been entirely conventional and is unrelated to the alternative medicine movement. Or, to put it bluntly, alternative cancer prevention is a contradiction in terms. Either it works in which case it is conventional medicine, or it doesn’t in which case it is not even an alternative but at best so-called alternative medicine.

 

The aims of this bibliometric analysis are to describe the characteristics of articles published on the efficacy of osteopathic interventions and to provide an overall portrait of their impacts in the scientific literature. A bibliometric analysis approach was used. Articles were identified with searches using a combination of relevant MeSH terms and indexing keywords about osteopathy and research designs in MEDLINE and CINAHL databases. The following indicators were extracted: country of the primary author, year of publication, journals, impact factor of the journal, number of citations, research design, participants’ age group, system/body part addressed, primary outcome, indexing keywords and types of techniques.

A total of 389 articles met the inclusion criteria. The number of empirical studies doubled every 5 years, with the United States, Italy, Spain, and the United Kingdom being the most productive countries. Twenty-three articles were cited over 100 times. Articles were published in 103 different indexed journals, but more than half (53.7%) of articles were published in one of three osteopathy-focused readership journals. Randomized control trials (n = 145; 37.3%) and case reports (n = 142; 36.5%) were the most common research designs. A total of 187 (48.1%) studies examined the effects of osteopathic interventions using a combination of techniques that belonged to two or all of the classic fields of osteopathic interventions (musculoskeletal, cranial, and visceral).

The authors concluded that this bibliometric analysis shows that publications about efficacy of osteopathy are relatively recent and have increased at a rapid pace over the last three decades. More than half of these publications are published in three osteopathic journals targeting a limited, disciplinary-focused readership. Our results highlight important needs for large efficacy and effectiveness trials, as well as study designs to further understanding of the mechanisms of action of the techniques being investigated. Finally, this bibliometric analysis can assist to identify osteopathy techniques and populations where further clinical research is required.

What the authors fail to state is that their analysis discloses osteopathy to be an area of utter unimportance. Less than 400 studies in 52 years is a dismal result. The fact that they were mostly published in journals of no impact makes it even worse. Twenty-three articles were cited more than 100 times; this is dismal! To put it in perspective, I have ~250 articles that were cited more than 100 times. Does that suggest that my work has made about 10 times more impact than the entire field of osteopathy?

Recently, I received this comment from a reader:

Edzard-‘I see you do not understand much of trial design’ is true BUT I wager that you are in the same boat when it comes to a design of a trial for LBP treatment: not only you but many other therapists. There are too many variables in the treatment relationship that would allow genuine , valid criticism of any design. If I have to pick one book of the several listed elsewhere I choose Gregory Grieve’s ‘Common Vertebral Joint Problems’. Get it, read it, think about it and with sufficient luck you may come to realize that your warranted prejudices against many unconventional ‘medical’ treatments should not be of the same strength when it comes to judging the physical therapy of some spinal problems as described in the book.

And a chiro added:

EE: I see that you do not understand much of trial design

Perhaps it’s Ernst who doesnt understand how to research back pain.

“The identification of patient subgroups that respond best to specific interventions has been set as a key priority in LBP research for the past 2 decades.2,7 In parallel, surveys of clinicians managing LBP show that there are strong views against generic treatment and an expectation that treatment should be individualized to the patient.6,22.”

Journal of Orthopaedic & Sports Physical Therapy
Published Online:January 31, 2017Volume47Issue2Pages44-48

Do I need to explain why the Grieve book (yes, I have it and yes, I read it) is not a substitute for evidence that an intervention or technique is effective? No, I didn’t think so. This needs to come from a decent clinical trial.

And how would one design a trial of LBP (low back pain) that would be a meaningful first step and account for the “many variables in the treatment relationship”?

How about proceeding as follows (the steps are not necessarily in that order):

  • Study the previously published literature.
  • Talk to other experts.
  • Recruit a research team that covers all the expertise you need (and don’t have yourself).
  • Formulate your research question. Mine would be IS THERAPY XY MORE EFFECTIVE THAN USUAL CARE FOR CHRONIC LBP? I know LBP is but a vague symptom. This does, however, not necessarily matter (see below).
  • Define primary and secondary outcome measures, e.g. pain, QoL, function, as well as the validated methods with which they will be quantified.
  • Clarify the method you employ for monitoring adverse effects.
  • Do a small pilot study.
  • Involve a statistician.
  • Calculate the required sample size of your study.
  • Consider going multi-center with your trial if you are short of patients.
  • Define chronic LBP as closely as you can. If there is evidence that a certain type of patient responds better to the therapy xy than others, that might be considered in the definition of the type of LBP.
  • List all inclusion and exclusion criteria.
  • Make sure you include randomization in the design.
  • Randomization should be to groups A and B. Group A receives treatment xy, while group B receives usual care.
  • Write down what A and B should and should not entail.
  • Make sure you include blinding of the outcome assessors and data evaluators.
  • Define how frequently the treatments should be administered and for how long.
  • Make sure all therapists employed in the study are of a high standard and define the criteria of this standard.
  • Train all therapists of both groups such that they provide treatments that are as uniform as possible.
  • Work out a reasonable statistical plan for evaluating the results.
  • Write all this down in a protocol.

Such a trial design does not need patient or therapist blinding nor does it require a placebo. The information it would provide is, of course, limited in several ways. Yet it would be a rigorous test of the research question.

If the results of the study are positive, one might consider thinking of an adequate sham treatment to match therapy xy and of other ways of firming up the evidence.

As LBP is not a disease but a symptom, the study does not aim to include patients that all are equal in all aspects of their condition. If some patients turn out to respond better than others, one can later check whether they have identifiable characteristics. Subsequently, one would need to do a trial to test whether the assumption is true.

Therapy xy is complex and needs to be tailored to the characteristics of each patient? That is not necessarily an unsolvable problem. Within limits, it is possible to allow each therapist the freedom to chose the approach he/she thinks is optimal. If the freedom needed is considerable, this might change the research question to something like ‘IS THAT TYPE OF THERAPIST MORE EFFECTIVE THAN THOSE EMPLOYING USUAL CARE FOR CHRONIC LBP?’

My trial would obviously not answer all the open questions. Yet it would be a reasonable start for evaluating a therapy that has not yet been submitted to clinical trials. Subsequent trials could build on its results.

I am sure that I have forgotten lots of details. If they come up in discussion, I can try to incorporate them into the study design.

 

 

Regular readers of this blog will know the US homeopath, Dana Ullman. He has been the star of several of my posts (for instance here, here, and here). Dana is prolific in his writing but he has published not published much in proper journals. Now he has almost doubled this list by publishing TWO (!) proper papers in real journals within just one month.

Congratulations, Dana!

The first is in CUREUS, a very unusual journal with a most unusual peer-review process. Allow me to show you the abstract of Dana’s article:

Homeopathic medicine is a controversial system of medicine that has been used worldwide for over 200 years. Recently, several governments, in part, owing to government-funded reviews of research on homeopathic medicine, have stopped reimbursements for homeopathic medicines and have discouraged their use by medical professionals. This review critically evaluates four government-funded reviews of clinical research on homeopathic medicine. An analysis of government-sponsored reviews of clinical research on homeopathic medicine was conducted, including two studies from Switzerland, one from England, and one from Australia. Three of the four government-funded reviews were critical of homeopathy, claiming that there was no reliable evidence that homeopathic medicines were effective. Three of these reviews had significant flaws, with potential ethical concerns raised in one of the reviews. The most comprehensive review of homeopathic research, including analysis of clinical and basic science concerns, found the most positive results for homeopathy.

The second paper was published in a journal called DOSE RESPONSE. The editor in chief of this journal is Prof E J Calabrese who has published numerous articles about homeopathy/hormesis. Here is the abstract of Dana’s 2nd article:

Serially diluted succussed solutions of a suitable drug/toxic substance can exhibit physicochemical and biological properties even far beyond Avogadro’s limit defying conventional wisdom. They can show hormesis, and homeopathy uses them as medicines. Many studies confirm that they can have an impact on gene expression different than controls. Water in the exclusion zone phase can have memory but for a short period. However, the nanoparticle as the physical substrate can hold information. Nanoparticle and exclusion zone duo as nanoparticle-exclusion zone shell can provide a prolonged memory. The Nanoparticle-Exclusion Zone Shell Model may be an important step toward explaining the nature and bioactivity of serially diluted succussed solutions used as homeopathic medicines. This model may also provide insight into the workings of hormesis. Hormesis is the primary phenomenon through which homeopathic phenomenon may have evolved exhibiting the principle of similars. Hahnemann exploited it to establish homeopathy. The nanoparticle-exclusion zone shells present in the remedy, selected on the principle of similars, can be patient-specific nanoparticles in a symptom syndrome-specific manner. They can carry the drug-specific information for safer clinical applications in an amplified form for high yielding. It suggests homeopathy is a type of nanopharmacology.

So, are Dana’s two articles significant? Both are reviews. The 1st tries to persuade us that homeopathy has clinical effects beyond placebo and that reports that say otherwise are full of errors and fraud and thus not reliable. The second tells us that these clinical effects of homeopathy can be explained by nano-pharmacology.

Is he right?

Please tell me what you think.

This study assessed the effects of being born under the zodiac sign Pisces on mortality. For that purpose, a retrospective observational study was conducted of the data from 26 Scandinavian intensive care units between 2009 and 2011. Patients aged 18 years or older with severe sepsis and in need of fluid resuscitation were included from the Scandinavian Starch for Severe Sepsis/ Septic Shock (6S) trial. The main outcome measure was the 90-day mortality.

The researchers included all 798 patients in the study; 70 (9%) of them were born under the sign of Pisces. The primary outcome (death within 90 days) occurred in 25 patients (35.7%) in the Pisces group, compared with 348 patients (48%) in the non-Pisces group (relative risk, 0.75; 95% CI, 0.54-1.03; one-sided P = 0.03).

The authors concluded that in a multicentre randomised clinical trial of IV fluids, being born under the sign of Pisces was associated with a decreased risk of death. Our study shows that with convenient use of statistics and an enticing explanatory hypothesis, it is possible to achieve significant findings in post-hoc analyses of data from large trials.

This is an excellent paper! It showcases the sort of nonsense one can do with datasets, statistics, and post hoc hypotheses. The authors entitled their article “Gone fishing in a fluid trial”, and this title should ensure that there are not some astrology nutters who mistake correlation for causation

… I hope

… but, of course, I am an optimist.

While working on yesterday’s post, I discovered another recent and remarkable article co-authored by Prof Harald Walach. It would surely be unforgivable not to show you the abstract:

The aim of this study is to explore experiences and perceived effects of the Rosary on issues around health and well-being, as well as on spirituality and religiosity. A qualitative study was conducted interviewing ten Roman Catholic German adults who regularly practiced the Rosary prayer. As a result of using a tangible prayer cord and from the rhythmic repetition of prayers, the participants described experiencing stability, peace and a contemplative connection with the Divine, with Mary as a guide and mediator before God. Praying the Rosary was described as helpful in coping with critical life events and in fostering an attitude of acceptance, humbleness and devotion.

The article impressed me so much that it prompted me to design a virtual study for which I borrowed Walach’s abstract. Here it is:

The aim of this study is to explore experiences and perceived effects of train-spotting on issues around health and well-being, as well as on spirituality. A qualitative study was conducted interviewing ten British adults who regularly practiced the art of train-spotting. As a result of using a tangible train-spotter diary and from the rhythmic repetition of the passing trains, the participants described experiencing stability, peace, and a contemplative connection with the Divine, with Mary as a guide and mediator before the almighty train-spotter in the sky. Train-spotting was described as helpful in coping with critical life events and in fostering an attitude of acceptance, humbleness, and devotion.

These virtual results are encouraging and encourage me to propose the hypothesis that Rosary use and train-spotting might be combined to create a new wellness program generating a maximum holistic effect. We are grateful to Walach et al for the inspiration and are currently applying for research funds to test our hypothesis in a controlled clinical trial.

 

Prince Charles has claimed that people struggling to return to full health after having the coronavirus should practice yoga. This is what the GUARDIAN reported about it on Friday:

In a video statement on Friday to the virtual yoga and healthcare symposium Wellness After Covid, the heir apparent said doctors should work together with “complementary healthcare specialists” to “build a roadmap to hope and healing” after Covid. “This pandemic has emphasised the importance of preparedness, resilience and the need for an approach which addresses the health and welfare of the whole person as part of society, and which does not merely focus on the symptoms alone,” Charles said. “As part of that approach, therapeutic, evidenced-informed yoga can contribute to health and healing. By its very nature, yoga is an accessible practice which provides practitioners with ways to manage stress, build resilience and promote healing…”

… Charles, who has previously espoused the benefits of yoga, is not the only fan in the royal family. His wife, the Duchess of Cornwall, has said “it makes you less stiff” and “more supple”, while Prince William has also been pictured doing yogic poses. In 2019, the Prince of Wales said yoga had “proven beneficial effects on both body and mind”, and delivered “tremendous social benefits” that help build “discipline, self-reliance and self-care”.

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END OF QUOTE

Yoga is a complex subject because it entails a host of different techniques, attitudes, and life-styles. There have been numerous clinical trials of various yoga techniques. They tend to suffer from poor study design as well as incomplete reporting and are thus no always reliable. Several systematic reviews have summarised the findings of these studies. A 2010 overview included 21 systematic reviews relating to a wide range of conditions. Nine systematic reviews arrived at positive conclusions, but many were associated with a high risk of bias. Unanimously positive evidence emerged only for depression and cardiovascular risk reduction.[1] There is no evidence that yoga speeds the recovery after COVID-19 or any other severe infectious disease, as Charles suggested.

Yoga is generally considered to be safe. However, a large-scale survey found that approximately 30% of yoga class attendees had experienced some type of adverse event. Although the majority had mild symptoms, the survey results indicated that patients with chronic diseases were more likely to experience adverse events.[2]  It, therefore, seems unlikely that yoga is suited for many patients recovering from a COVID-19 infection.

The warning by the Vatican’s chief exorcist that yoga leads to ‘demonic possession’[3] might not be taken seriously by rational thinkers. Yet, experts have long warned that many yoga teachers try to recruit their clients into the more cult-like aspects of yoga.[4]

Perhaps the most remarkable expression in Charles’ quotes is the term ‘EVIDENCE-INFORMED‘. It crops up regularly when Charles (or his advisor Dr. Michael Dixon) speaks or writes about so-called alternative medicine (SCAM). It is a clever term that sounds almost like ‘evidence-based’ but means something entirely different. If a SCAM is not evidence-based, it can still be legitimately put under the umbrella of ‘evidence-informed’: we know the evidence is not positive, we were well-informed of this fact, we nevertheless conclude that yoga (or any other SCAM) might be a good idea!

In my view, the regular use of the term ‘evidence-informed’ in the realm of SCAM discloses a lack of clarity that suits all snake-oil salesmen very well.

 

[1] Ernst E, Lee MS: Focus on Alternative and Complementary Therapies Volume 15(4) December 2010 274–27

[2] Matsushita T, Oka T. A large-scale survey of adverse events experienced in yoga classes. Biopsychosoc Med. 2015 Mar 18;9:9. doi: 10.1186/s13030-015-0037-1. PMID: 25844090; PMCID: PMC4384376.

[3] https://www.social-consciousness.com/2017/06/vaticans-chief-exorcist-warns-that-yoga-causes-demonic-possession.html

[4] https://www.theguardian.com/lifeandstyle/2020/jun/26/experience-my-yoga-class-turned-out-to-be-a-cult

 

Mind-body interventions (MBIs) are one of the top ten so-called alternative medicine (SCAM) approaches utilized in pediatrics, but there is limited knowledge on associated adverse events (AE). The objective of this review was to systematically review AEs reported in association with MBIs in children.

Electronic databases MEDLINE, Embase, CINAHL, CDSR, and CCRCT were searched from inception to August 2018. The authors included primary studies on participants ≤ 21 years of age that used an MBI. Experimental studies were assessed for whether AEs were reported on or not, and all other study designs were included only if they reported an AE.

A total of 441 were included as primary pediatric MBI studies. Of these, 377 (85.5%) did not explicitly report the presence/absence of AEs or a safety assessment. In total, there were 64 included studies: 43 experimental studies reported that no AE occurred, and 21 studies reported AEs. A total of 37 AEs were found, of which the most serious were grade 3. Most of the studies reporting AEs did not report on severity (81.0%) or duration of AEs (52.4%).

The authors concluded that MBIs are popularly used in children; however associated harms are often not reported and lack important information for meaningful assessment.

SCAM is far too often considered to be risk-free. This phenomenon is particularly stark if the SCAM in question does not involve physical or pharmacological treatments. Thus MBIs are seen and often waved through as especially safe. Consequently, many researchers do not even bother to monitor AEs in their clinical trials. This might be understandable, but it is nevertheless a violation of research ethics.

This new review is important in that it highlights these issues. It is high time that we stop giving researchers in SCAM the benefit of the doubt. They may or may not make honest mistakes when not reporting AEs. In any case, it is clear that they are not properly trained and supervised. All too often, we still see clinical trials run by amateurs who have little idea of methodology and even less of ethics. The harm this phenomenon does is difficult to quantify, but I fear it is huge.

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