Patients with fibromyalgia (FM) frequently resort to so-called alternative medicine (SCAM). In particular, osteopathy seems to be common, despite very weak supporting evidence. This study aimed to assess the efficacy of osteopathic manipulation in FM in a randomized clinical trial.

Patients were randomized to osteopathic or sham treatment. Treatment was administered by experienced physical medicine physicians, and consisted of 6 sessions per patient, over 6 weeks. Treatment credibility and expectancy were repeatedly evaluated. Patients completed standardized questionnaires at baseline, during treatment, and at 6, 12, 24, and 52 weeks after randomization. The primary outcome was pain intensity (100-mm visual analog scale) during the treatment period. Secondary outcomes included fatigue, functioning, and health-related quality of life. Intention-to-treat analyses were performed adjusted for credibility, using multiple imputations for missing data.

The ‘real’ treatment consisted of the following maneuvers. The patient was first placed in a prone position. Each vertebra from C7 to L5 was mobilized in a dorsoventral direction by progressive pressure on the spinous process (SP), and in rotation by applying pressure on the lateral surface of the SP (bilaterally). The sacral bone was repeatedly mobilized in nutation–counternutation (5–10 times). The piriformis muscles were progressively stretched. The hip joint was then progressively mobilized in extension combined with abduction and adduction to stretch the adductor, abductor, and flexor muscles (10 times). The shoulders were progressively mobilized, one by one, with a repeated circumduction movement of the glenohumeral joint (10 times). The patient was then placed in a supine position, for the following maneuvers. At the neck, bimanual traction was performed, followed by repeated mobilization in lateral flexion and in rotation (both sides, five times, 3–5 times each). At the shoulders, cranial traction was performed of both arms and then a repeated caudal traction of one arm and then the other, by blocking the clavicle, thereby opening the acromioclavicular and glenohumeral joints (three times). At the hips, repeated tractions were performed on the legs (three times) and the hip joint was mobilized by circumduction movements. Finally, the patient was placed in the lateral decubitus position for mobilization of the lumbar and thoracolumbar spine. Thrust manipulations were allowed at any level, according to the patient’s complaint.

The sham treatment followed the same order, but the maneuvers were stopped halfway through to prevent joint mobilization at the spine. At the hips and shoulders, the stretching techniques were also stopped halfway. The joint techniques were simulated, with no significant mobilization. Thrust manipulation was forbidden.

In total, 101 patients (94% women) were included. Osteopathic treatment did not significantly decrease pain relative to sham treatment (mean difference during treatment: -2.2 mm; 95% confidence interval, -9.1 to 4.6 mm). No significant differences were observed for secondary outcomes. No serious adverse events were observed, despite a likely rebound in pain and altered functioning at week 12 in patients treated by osteopathy. Patient expectancy was predictive of pain during treatment, with a decrease of 12.9 mm (4.4-21.5 mm) per 10 points on the 0-30 scale. Treatment credibility and expectancy were also predictive of several secondary outcomes.

The authors concluded that osteopathy conferred no benefit over sham treatment for pain, fatigue, functioning, and quality of life in patients with FM. These findings do not support the use of osteopathy to treat these patients. More attention should be paid to the expectancy of patients in FM management.

A recent systematic review concluded that the current evidence of manual therapy in patients with FM, based on a very low to moderate quality of evidence, was inconclusive and insufficient to support and recommend the use of manual therapy in this population. To date, only general osteopathic treatment has achieved clinically relevant pain improvement when compared with control.

The new study is by far the most rigorous one to date. This means, I think, that the best available evidence confirms that, in the management of FM,

osteopathy is a placebo therapy.

PS

When I say ‘osteopathy’ I mean the treatments as taught by Andrew Still. US osteopathy practice conventional medicine but everywhere else they adhere more or less strongly to Still’s ideas.

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!

Young Australian journalist Eammon Ashton-Atkinson has survived COVID-19 and two strokes, all in the span of a month. It was reported that the 34-year-old Washington DC-based correspondent had a stroke on his chiropractor’s table after experiencing post-COVID neck pain, and was rushed to hospital. While recovering at home, he had a second stroke, losing his balance and collapsing.

He told his radio channel that the first stroke occurred while he was still on the chiropractor’s bench. He was rushed to hospital where a dissection of an artery supplying the brain (probably the vertebral artery) was diagnosed. His vision was initially severely disturbed and he had ‘pins and needles’ in parts of his body. These symptoms subsided rapidly and he was discharged home to recover. However, while resting at his home in DC, he suffered another stroke. This time a blood clot from the dissection fired into the part of his brain responsible for his balance. He was then readmitted to the hospital and treated against the blood clot. Now he is again back home and hoping to recover fully.

Were the strokes related to COVID, the vaccination, or to the chiropractic treatment? Definitely the latter, explains Eammon Ashton-Atkinson in the interview. It seems that his doctors diagnosing and treating the strokes were clear that the cause of the problems was the manipulation.

“It’s still quite traumatic to talk about,” Eammon Ashton-Atkinson told Jim Wilson. “In some ways, I’m very unlucky, in other ways I’m extremely lucky because I’m talking to you now.”

Chiropractors will surely point out that this is not a properly documented case. Almost every detail that makes a decent case report is missing.

I agree!

And why are cases like these (one might speculate that there are many of them) not adequately documented?

Because there is no post-marketing surveillance of chiropractic.

And who is responsible for establishing one?

The chiropractors, of course!

And why do they not create reliable post-marketing surveillance?

Perhaps because that would disclose the magnitude of the risk; and that would obviously be very bad for business.

Therefore, I suggest that chiropractors finally get their act together and create adequate post-marketing surveillance. Until they have done so, they have no moral right to complain that cases like the one above are not adequately documented.

By guest blogger Hans-Werner Bertelsen

Veronika Hackenbroch wrote in an article for the German news website Der Spiegel about clusters of cases where children were born with severe birth deformities. (1) The only common factor that researchers in the Paediatrics department of the University Medical Center Mainz were able to identify through intensive communication with the mothers was that they had all visited a dentist whilst pregnant. The fetus is particularly sensitive to exogenous stimuli during early pregnancy, which is why this period is also known as the “teratogenetic determination period” (Koberg).

The data regarding the workplace exposure limit for mercury is outdated – it is based on information collected about 50 years ago in some cases. Since that time, there have been considerable advances, in particular in the fields of measuring technology and analysis. Unfortunately, these advances have yet to be utilized to provide meaningful figures on exposure to mercury vapour when removing old fillings or drilling into teeth with mercury amalgam fillings for the purpose of acute pain management. In addition to patient protection, the focus when processing existing mercury amalgam fillings is therefore also on occupational health and safety. This has not gone unnoticed by many female employees in dental surgeries that mercury amalgam can pose serious risks to unborn children. For example, a study in Norway reported an increased risk of perinatal death associated with a high number of mercury amalgam fillings. (2)

Sylvia Gabel from the German Association of Medical Professions (Verband medizinischer Fachberufe e.V.) even called for an immediate ban on toxic mercury amalgam: “Vapours pose a danger to dental professionals’ health!”. Mrs Gabel added: “The processing of amalgam in dental surgery releases mercury vapour. As 99 per cent of the dental nurses and hygienists in Germany are female and mercury has harmful effects on both fertility and the unborn child, we are exposed to a particular risk.”(3)

Researchers in Norway documented a considerable increase in the concentration of mercury in the blood after the removal of fillings as far back as 2006. (4) Toxicologists are in unanimous agreement that these peaks, which are the result of inhalation, are extremely harmful and may well have a teratogenetic effect in early pregnancy. (5) Consequently, what I am calling for is this: until such time as we know how high the mercury vapour concentrations are and as long as we “remain in the dark”, we should refrain from removing existing fillings containing mercury and performing dental drilling procedures in women of child-bearing age for ethical reasons so as to exclude the risk of deformities (see Der Spiegel article: “Waren die Schwangeren beim Zahnarzt?”, V. Hackenbroch, 20.09.19). (6)

An immediate ban on the use of mercury amalgam would be advantageous not solely with regard to the exposure to toxins of cancer patients, as the field of “alternative medicine” often recommends expensive, unnecessary and subsequently also very harmful “detox” treatments. (7) A more than questionable business from an ethical perspective: cancer patients are often looking for additional, so-called complementary therapy methods. This often sees them fall into the clutches of healers and doctors, who have no dental expertise but can identify mercury amalgam fillings very easily due to their dark colour. As I myself experienced in a so-called “alternative” dental surgery, the frightened patients, who are often in the middle of chemotherapy cycles, are then informed that they absolutely must have the mercury amalgam removed and then undergo a “detoxification therapy”. Introjects are not spared in the process: “Your body, already devastated by the chemotherapy, should not be subjected to additional chemicals.” Of course, this “detoxification” will be performed (with maximum consideration!) as a “homoeopathic” therapy. I had to observe this very lucrative “business model” often enough – and not once has a cancer patient objected. Once they fall under the charlatan’s spell, patients will allow themselves to be treated with all manner of things. Even live cells. In one patient, a single mother of two, this method triggered a fatal anaphylactic shock. (8) However, cancers and other chronic diseases are not the only reasons that bring patients with mercury amalgam fillings within the reach of dubious individuals with promises of salvation and charlatans. (9) An unfulfilled desire to have children has also led countless desperate women to ask to be parted irrevocably from their mercury-containing fillings. German health insurance companies approve these interventions, which appear logical from a toxicological perspective, and thus contribute not only to the replacement of the fillings but also to the release of mercury vapours and thus toxic peaks resulting from inhalation. Such actions can even have fatal consequences in the early stages of pregnancy.

However, the focus with mercury amalgam is not only on protecting patients from dishonest therapists and unnecessary teratogenetic risks – female staff could also benefit in general. For example, an immediate ban of the use of mercury amalgam could significantly increase job satisfaction among female employees in the dental surgery. According to Sylvia Gabel: “Strike measures were considered in the surgeries continuing use.”(10)

Each new mercury amalgam filling brings with it numerous side effects. It:

• – increases the risk of toxic exposure resulting from inhalation during removal;
• – increases the risk of corrosion products developing in the long term;
• – increases demand in the field of detox beliefs and homoeopathic charlatanry;
• – promotes the conspiracy narrative of “the dangers of conventional medicine”; and, in doing so,
• – often undermines patients’ confidence in treatments appropriate for the indication and, along with it, the often-vital compliance;
• – fills not only the cavity in the tooth but also the charlatans’ pockets.

I believe it is time to give dental health a helping hand with an intelligent combination of contemporary prevention concepts and harmless filling materials. Currently, the political will is merely a small seed. The seed must now germinate and grow.

REFERENCES

1. “Waren die Schwangeren beim Zahnarzt?”, V. Hackenbroch, 20.09.19 2. https://www.zwp-online.info/zwpnews/dental-news/wissenschaft-und-forschung/schwangerschaft-und-amalgam-risiken-bei-hohen-mengen 3. https://www.dzw.de/amalgam-ausstieg-ngo 4. https://pubmed.ncbi.nlm.nih.gov/29320025/

5. Prof. Eschenhagen, Toxicology Hamburg-Eppendorf in personal correspondence dated 23.01.2020 6. Comment dated 05.07. https://onkelmichael.blog/2021/07/03/ist-eine-entfernung-bestehender- amalgam-restaurationen-problemlos-und-bedenkenlos-durchfuhrbar/comment-page-1/? unapproved=4000&moderation-hash=d5b63e66f5045bfa12d829a88eddf1b0#comment- 4000 7. Prof. E. Ernst: https://www.theguardian.com/lifeandstyle/2014/dec/05/detox-myth-health-diet-science-ignorance 8. http://scienceblogs.de/kritisch-gedacht/2012/02/08/insider-bericht/

9. Prof. Jutta Hübner (Oncology, Jena) in personal correspondence dated 21.01.2020

10. Sylvia Gabel in personal correspondence dated 18.06.21

Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, this study evaluated if daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors.

A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups:

• 16 were administered AB (330 mL/day),
• 7 to NAB (660 mL/day),
• 14 were in the control group and received no beer.

After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms. Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.

The authors concluded that a daily moderate AB and NAB consumption may provide an alternative approach for postmenopausal women seeking relief from mild to moderate climacteric symptoms. Moreover, NAB was found to have a beneficial effect on LDL-C, ApoA1, and DBP measurements, all known risk factors for cardiovascular disease. However, these results must be considered as preliminary and will require confirmation with larger sample sizes.

The clinical implications of daily moderate AB and NAB consumption have been revealed in this study, but the mechanisms of action and impacts on sex hormones remain unknown. The most effective quantity of beer, with or without alcohol, that can be safely consumed by a postmenopausal woman still needs to be determined, taking into consideration factors such as age, genetics, and ethnicity.

I am impressed and only have this comment: let’s please not forget the male menopause …

and if they ever did a trial, can I please go in group AB?

Germany has long been the ‘Promised Land’ for so-called alternative medicine (SCAM). For many years, about two-thirds of the general population has been reported to be regular SCAM users. Now, this seems about to change. A recent survey found that only one-third of Germans believe that homeopathy works as well as conventional medicine. The verdict on SCAM as a whole is similar: Only 35 percent of respondents would like SCAM to play a role in healthcare in addition to modern medicine. The results originate from an extensive representative survey commissioned by the GWUP and carried out by the KANTAR Institute to sound out attitudes toward esotericism and pseudoscience. The figure below depicts percentage figures of the belief in (from left to right) homeopathy, integrated medicine, spiritual healing, electrosmog, dowsing, clairvoyance, psychokinesis, ghosts, astrology, extra-terrestrials, none mentioned.

“It is a good sign for health care if two-thirds of the population reject dubious cures. The experience from the pandemic shows that we can only fight diseases with science and modern medicine,” stated Amardeo Sarma, chairman of GWUP. “I am pleased with the result because it also underlines the impact of our educational work. I’m convinced that we’re helping people make important decisions, removing uncertainty and, not least, preventing suffering caused by incorrect treatments.”

“As a physician, I am pleased when more and more people are concerned with their health and critically question promises of healing,” said Dr. Natalie Grams. “For me, the declining approval of homeopathy means that it is worthwhile to publicly stand by science and not be muzzled by industry interests. Fewer homeopathics mean more good medicine for patients that really works.”

This sounds like good news indeed. Yet, I think, we need to be careful and avoid jumping to conclusions because prevalence surveys are often not as reliable as they seem.

1) They frequently lack a clear definition of what is being surveyed. There is no generally accepted definition of alternative medicine, and even if the researchers address specific therapies, they run into huge problems. Take integrated medicine, for instance – some see this as alternative medicine, while others would, of course, argue that it is the integration of social and health care. Or take homeopathy – many consumers confuse it with herbal medicine.

2) The questionnaires used for such surveys are rarely validated. Essentially, this means that we cannot be sure they evaluate what we think they evaluate. We all know that the way we formulate a question can determine the answer. There are many potential sources of bias here, and they are rarely taken into consideration. It is therefore not surprising that different surveys report different prevalences. In Indonesia, for instance, an increase in SCAM use has been reported associated with the pandemic.

3) The typical survey has a low response rate; sometimes the response rate is not even provided or remains unknown even to the investigators. This means we do not know how the majority of patients/consumers who received but did not fill the questionnaire would have answered. Often there is good reason to suspect that those who have a certain attitude did respond, while those with a different opinion did not. This self-selection process is likely to produce misleading findings.

4) The typical survey has a long list of questions and reports only those results that the investigators find interesting or pleasing. Such selective reporting can introduce a significant bias that may not be detectable for the reader of the report.

I am sure the new survey is not seriously affected by any of these drawbacks. After all, it is from the GWUP, the Society of the Scientific Study of Para-Sciences. If they are not able to do good science, who is?

My most frequently cited paper was published by Angelo Izzo and myself in 2001. It has so far been cited 1612 times. Here is its abstract:

Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions between the seven top-selling herbal medicines (ginkgo, St John’s wort, ginseng, garlic, echinacea, saw palmetto and kava) and prescribed drugs. Literature searches were performed using the following databases: Medline (via Pubmed), Cochrane Library, Embase and phytobase (all from their inception to July 2000). All data relating to herb-drug interactions were included regardless of whether they were based on case reports, case series, clinical trials or other types of investigation in humans. In vitro experiments were excluded. Data were extracted by the first author and validated by the second author. 41 case reports or case series and 17 clinical trials were identified.

The results indicate that St John’s wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine. Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken with chlorpropamide. Kava (Piper methysticum) increases ‘off periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and saw palmetto (Serenoa repens).

In conclusion, interactions between herbal medicines and synthetic drugs exist and can have serious clinical consequences. Healthcare professionals should ask their patients about the use of herbal products and consider the possibility of herb-drug interactions.

The article was so successful that the journal ‘DRUGS’ asked us to publish an update. As the journal is highly respected we obliged with pleasure; here is the abstract of the update of 2009:

The concomitant use of herbal medicines and pharmacotherapy is wide spread. We have reviewed the literature to determine the possible interactions between seven popular herbal medicines (ginkgo, St John’s wort, ginseng, garlic, echinacea, saw palmetto and kava) and conventional drugs. Literature searches were performed using MEDLINE, Cochrane Library and EMBASE and we identified 128 case reports or case series, and 80 clinical trials. Clinical trials indicate that St John’s wort (Hypericum perforatum), via cytochrome P450 (CYP) and/or P-glycoprotein induction, reduces the plasma concentrations (and/or increases the clearance) of alprazolam, amitriptyline, atorvastatin, chlorzoxazone, ciclosporin, debrisoquine, digoxin, erythromycin, fexofenadine, gliclazide, imatinib, indinavir, irinotecan, ivabradine, mephenytoin, methadone, midazolam, nifedipine, omeprazole, oral contraceptives, quazepam, simvastatin, tacrolimus, talinolol, verapamil, voriconazole and warfarin. Case reports or case series suggest interactions of St John’s wort with adrenergic vasopressors, anaesthetics, bupropion, buspirone, ciclosporin, eletriptan, loperamide, nefazodone, nevirapine, oral contraceptives, paroxetine, phenprocoumon, prednisone, sertraline, tacrolimus, theophylline, tibolone, tryptophan, venlafaxine and warfarin. Ginkgo (Ginkgo biloba) decreases the plasma concentrations of omeprazole, ritonavir and tolbutamide. Clinical cases indicate interactions of ginkgo with antiepileptics, aspirin (acetylsalicylic acid), diuretics, ibuprofen, risperidone, rofecoxib, trazodone and warfarin. Ginseng (Panax ginseng) may interact with phenelzine and warfarin. Kava (Piper methysticum) increases the clearance of chlorzoxazone (a CYP2E1 substrate) and may interact with alprazolam, levodopa and paroxetine. Garlic (Allium sativum) interacts with chlorpropamide, fluindione, ritonavir and warfarin; it also reduces plasma concentrations of chlorzoxazone (a CYP2E1 probe). Echinacea might affect the clearance of caffeine (a CYP1A2 probe) and midazolam (a CYP3A4 probe). No interactions have been reported for saw palmetto (Serenoa repens). Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several interactions, particularly those with St John’s wort, may have serious clinical consequences.

Angelo Izzo is a lovely man and a highly skilled pharmacologist. He came to my department in 2000 as a guest researcher (on his own funds) and worked with us for several months. This is how the 2001 paper was created. After he returned to his native Naples, Italy, he became a professor of pharmacology with a special interest in plant pharmacology. He has published many further important papers and, together with his Italian colleagues, a most useful book entitled ‘Phytotherapy: A Quick Reference to Herbal Medicine‘. I warmly recommend it to anyone interested in herbal medicine.

The subject of herb-drug interactions is in my view hugely important. When Angelo and I first approached it in 2001, it was woefully under-researched; in that year, there were just 37 Medline-listed papers on the subject. This has now increased very significantly; since 2011 there are about 150 articles on the topic each year. It is tempting to think that Angelo (and I) had a tiny influence on this positive development.

Acupuncture has been widely used for acute low back pain (LBP), yet there remains continued controversy regarding its efficacy. Therefore, this systematic review aimed at evaluating the evidence.

English and Chinese databases were searched for randomized controlled trials (RCTs) of acupuncture for acute LBP published up to May 2020. Data on the outcomes of pain intensity, functional status, and analgesic use were extracted. The meta-analysis was performed using the Cochrane Collaboration’s RevMan 5.3, and pooled data were expressed as mean differences (MD) with 95% confidence intervals (CIs).

Of the 13 eligible RCTs identified, 9 were from China, one each from Brazil, the United Kingdom, Australia, and South Korea. Four studies were published in English, and 9 were published in Chinese. The 13 RCTs (involving 707 patients) provided moderate-quality evidence that acupuncture has a statistically significant association with improvements in VAS (visual analog scale) score [MD: −1.75 (95% CI: −2.39, −1.12)]. Two studies indicated that acupuncture did not influence the RMDQ (Roland-Morris Disability Questionnaire) scores more than the control treatment [MD: −2.34 (95% CI: −5.34, 0.67)]. Three studies suggested that acupuncture influenced the ODI (Oswestry Disability Index) scores more than the control treatment [MD: −12.84 (95% CI: −23.94, −1.74)]. Two studies suggested that acupuncture influenced the number of pills more than the control treatment [MD: −3.19 (95% CI: −3.45, −2.92)]. Merely 2 RCTs were sham-controlled and only 4 of the 13 RCTs mentioned adverse effects.

The authors concluded that acupuncture treatment of acute LBP was associated with modest improvements in the VAS score, ODI score, and the number of pills, but not the RMDQ score. Our findings should be considered with caution due to the low power original studies. High-quality trials are needed to assess further the role of
acupuncture in the treatment of acute LBP.

I do appreciate the authors’ call for caution in interpreting the findings. Yet, I feel that much more caution than the authors advise is needed here:

• Most studies are from China, and we have often seen that these trials cannot be trusted.
• Only 2 RCTs are sham-controlled which means that most studies failed to control for placebo effects.
• Most studies do not mention adverse effects, confirming the unethically low standards of these investigations.

I am afraid that this new review does not inspire me with confidence that acupuncture is an effective therapy for acute LBP.

Google Scholar is quite a fantastic tool; I recently (20/5/2021) glanced at my own profile and decided to have a closer look at the 100 of my papers that have been cited most frequently. The list below shows these ‘top 100’; in the 1st column is the reference (title of the article, authors, journal). In the MIDDLE column are the numbers of times each paper has been cited (if you click on it, you see the articles that cited the paper in question), and the far-right column tells you the year of publication.

Here we go:

What my analysis of these data suggests is the following:

1. Only relatively few articles (n=8) are in the ‘top 100’ that I published before I took up the Exeter post starting full-time research into so-called alternative medicine (SCAM).
2. Despite the fact that in any such analysis older papers are at a significant advantage over newer articles, the vast majority of these 100 papers are relatively recent.
3. Very few of our clinical trials are in the ‘top 100’, even though I did publish well over 50 during my career.
4. Systematic reviews dominate by far and amount to 49 of the ‘top 100’.
5. Even some of my ‘letters to the editor’ did make it into the ‘top 100’.
6. Six of the 100 papers are surveys.
7. As to the SCAM topics, most articles are on herbal medicine (n=39), followed by acupuncture (13), manual therapies (4), and homeopathy (2).
8. A total of 21 of the papers have their main focus on safety issues.
9. The vast majority of the papers are co-authored by more than one member of my team.
10. A total of 22 articles were produced in collaboration with researchers who were not members of my team.
11. Seventeen papers were single-author papers by myself.
12. Even though I certainly did publish a lot in journals specialized in so-called alternative medicine (SCAM), only very few of these articles made it into this list.

There are many things that I find interesting in all this. Perhaps just a few points:

• The two SCAM areas in which I have published many articles and do get a lot of flack for what I have written are homeopathy and chiropractic. Surprisingly, not many of these papers are in the ‘top 100’. I am not sure whether this is meaningful and if so how I should interpret this.
• The fact that hardly any papers published in SCAM journals made the ‘top 100’ is interesting but not surprising. It means that researchers who want to see their work cited – and who doesn’t? – should avoid such journals (there are, of course, other reasons as well for avoiding such journals).
• The fact that even ‘letters to the editors’ can get cited so frequently seems unexpected but I find it encouraging.
• Collaboration with researchers who are not from one’s own team can be, in my experience, cumbersome but it is worth it and often fruitful.
• If you asked me, is there a correlation between the quality of a paper and the frequency with which it is cited, I’d have to say NO.
• If you asked me, is there a correlation between the importance of a paper and the frequency with which it is cited, I’d have to say NO again.

If you thought that osteopathy is for spinal problems, think again. This study aimed to determine whether osteopathic manipulation of the T9-T10 vertebrae improves the evolution of tonsillitis. A randomized, stratified, controlled clinical trial with blinded patients, evaluator, and data analyst was performed.

The patients in the control group (CG) received a “sham” manipulation consisting of a 150° passive flexion of the shoulders, with a gentle contact of the osteopath’s knees in the middle thoracic vertebrae, without impulse or causing tension. A high-speed, low-amplitude technique was applied to the T9-T10 vertebrae in the osteopathic manipulative group (OMG) patients.

The number of days needed to resolve the tonsillitis was significantly lower (p = 0.025) in the OMG (2.03 ± 0.95 days) than the CG (2.39 ± 0.82 days). Additionally, the number of episodes of tonsillitis after the treatment decreased significantly more in the OMG (0.8 ± 1.88 episodes/year in total) than the CG (2 ± 2.12) (p = 0.005). In the OMG, 60.8% had no recurrences of tonsillitis, compared to 22.5% of the CG, in the following year (χ² (1) = 15.57, p < 0.001). No patients reported adverse effects.

The authors concluded that during an episode of tonsillitis, the number of days to resolution was significantly lower after the application of an osteopathic manipulation of the T9-T10 vertebrae, compared to a sham manipulation. The number of subsequent year tonsillitis episodes was greatly reduced in both groups, significantly more in the OMG than in the CG patients.

This is an interesting study. Its exceptional feature is that it is sham-controlled. This must mean that the results are reliable and that osteopathic manipulation is indeed an effective treatment of tonsillitis.

Or perhaps not?

It is, of course, most laudable to introduce a sham control group into such a study. But let us for a moment reflect on what purpose it serves. Its main purpose, no doubt, is to render patients unaware of which treatment they received, sham or verum. This is only possible if the sham is indistinguishable from the verum. In this study, this was clearly not the case. Patients in the verum group felt that they received the verum, and patients in the sham group felt that they had the placebo. Thus the former expect to get better, while the latter don’t.

So, we are left with two very different interpretations of the findings:

1. Osteopathic manipulations are effective for tonsillitis.
2. Osteopathic manipulations are not effective for tonsillitis, but the patients’ expectations determined the outcomes.

Which is more likely?

What do you think?