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

systematic review

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Resveratrol is one of the most popular dietary supplements. It is an antioxidant found in red grape skin, Japanese knotweed, blueberries and other berries. Resveratrol is available as dietary supplements from red wine extracts, grape seed extracts, Japanese knotweed extracts and other plants. The amount and purity of resveratrol in supplements varies significantly; absorption in the gut is low.

While, for many supplements, there is no or very little research, this one has a huge amount. So, has reseveratrol any proven health effects demonstrated in clinical trials?

The answer is encouraging.

This abstract provides a useful summary:

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer’s disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5′-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH-associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.

This is a comprehensive review but it fails to critically assess the quality of the clinical trials. Once we do that, we are likely to get disappointed. Many studies are just not up to the mark.

And if we consult a Cochrane review, our enthusiasm for resveratrol disappears completely: Currently, research is insufficient for review authors to evaluate the safety and efficacy of resveratrol supplementation for treatment of adults with T2DM [type 2 diabetes mellitus]. The limited available research does not provide sufficient evidence to support any effect, beneficial or adverse, of four to five weeks of 10 mg to 1000 mg of resveratrol in adults with T2DM. Adequately powered RCTs reporting patient-relevant outcomes with long-term follow-up periods are needed to further evaluate the efficacy and safety of resveratrol supplementation in the treatment of T2DM.

So, for the time being, I might just continue to obtain my resveratrol in very small but regular doses from red wine, I think.

 

 

Many hundreds of plants worldwide have a place in folk medicine as treatments for microbial infections and antimicrobial activity of extracts in vitro may be readily assessed in microbiology laboratories. Many so tested are reported to show inhibitory effects against a range of organisms. For less than responsible entrepreneurs, this is often enough reason to promote them as therapeutic options.

But laboratory testing can at best be only a very crude, though relatively inexpensive and rapid screen, while in vivo testing is very costly and time consuming. On this background, we conducted a review in 2003 to examine the range of plants or herbs that have been tested for antiviral properties in laboratories, animals and humans. Here is its abstract:

Background and aims: Many antiviral compounds presently in clinical use have a narrow spectrum of activity, limited therapeutic usefulness and variable toxicity. There is also an emerging problem of resistant viral strains. This study was undertaken to examine the published literature on herbs and plants with antiviral activity, their laboratory evaluation in vitro and in vivo, and evidence of human clinical efficacy.

Methods: Independent literature searches were performed on MEDLINE, EMBASE, CISCOM, AMED and Cochrane Library for information on plants and herbs with antiviral activity. There was no restriction on the language of publication. Data from clinical trials of single herb preparations used to treat uncomplicated viral infections were extracted in a standardized, predefined manner.

Results: Many hundreds of herbal preparations with antiviral activity were identified and the results of one search presented as an example. Yet extracts from only 11 species met the inclusion criteria of this review and have been tested in clinical trials. They have been used in a total of 33 randomised, and a further eight non-randomised, clinical trials. Fourteen of these trials described the use of Phyllanthus spp. for treatment of hepatitis B, seven reporting positive and seven reporting negative results. The other 10 herbal medicines had each been tested in between one and nine clinical trials. Only four of these 26 trials reported no benefit from the herbal product.

Conclusions: Though most of the clinical trials located reported some benefits from use of antiviral herbal medicines, negative trials may not be published at all. There remains a need for larger, stringently designed, randomised clinical trials to provide conclusive evidence of their efficacy.

One of the herbal remedies that seemed to show some promise specifically for upper respiratory infections was Andrographis paniculata. This evidence prompted us in 2004 to conduct a systematic review focused on this herb specifically. Here is its abstract:

Acute respiratory infections represent a significant cause of over-prescription of antibiotics and are one of the major reasons for absence from work. The leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used as a medicinal herb in the treatment of infectious diseases. Systematic literature searches were conducted in six computerised databases and the reference lists of all papers located were checked for further relevant publications. Information was also requested from manufacturers, the spontaneous reporting schemes of the World Health Organisation and national drug safety bodies. No language restrictions were imposed. Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Adverse events reported following administration of A. paniculata were generally mild and infrequent. There were few spontaneous reports of adverse events. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.

Before you now rush to buy a dietary supplement of A. paniculata, let me stress this in no uncertain terms: the collective evidence is at best suggestive, but it is not compelling. Importantly, there is, to the best of my knowledge, no sound evidence that any herbal remedy is effective in preventing or treating Covid-19 infections.

I truly wished to be able to report more encouraging news, but the truth is the truth, even (I would argue, particularly) in desperate times.

This ‘Manifesto of the European Committee for Homeopathy (ECH) and the European Federation of Homeopathic Patients Associations (EFHPA)‘ has just been published. It is worth considering in more detail, I think. So, I will first reproduce the document in its entirety and subsequently provide some critical assessment of it.

Homeopathy: a solution for major healthcare problems in the EU

  • Helps to reduce the need of antibiotics in human and veterinary health care, thus reducing the problem of antimicrobial resistance [i],[ii]
  • Increases quality of life and reduces severity of complaints in patients with chronic disease, when integrated in health care [iii],[iv],[v],[vi],[vii],[viii]
  • Can reduce the use of long-term conventional prescription drugs, when integrated in health care [ix]

Homeopathy: safe and cost-effective with a high patient satisfaction

  • Can lead to lower health care costs, when integrated in health care, [x],[xi],[xii],
  • Is safe, with high patient satisfaction [xiii],[xiv],[xv],[xvi]
  • Patients using homeopathy have better outcomes than users of conventional treatment, with similar costs [xvii]
  • Quality, safety and correct labelling of homeopathic products is guaranteed by Directive 2001/83 EC

 EU consumers expect and demand homeopathy as part of their health care

  • Reported as the most used medical complementary medicine in Europe [xviii]
  • Three out of four European citizens know about homeopathy and out of them 29% use it for their day-to day health care [xix]

 Scientific evidence of the highest calibre confirms the clinical efficacy of homeopathic   medicine

There is convincing evidence for biological efficacy of homeopathic medicine

  • Irrefutable scientific evidence has been published on the positive effects of homeopathic products in laboratory settings [xxvii],[xxviii]

References

[i] Grimaldi-Bensouda L, Bégaud B, Rossignol M, et al. Management of upper respiratory tract infections by different medical practices, including homeopathy, and consumption of antibiotics in primary care: the EPI3 cohort study in France 2007-2008. PLoS One. 2014 Mar 19;9(3):e89990

[ii] Camerlink I, Ellinger L, Bakker EJ, Lantinga EA. Homeopathy as replacement to antibiotics in the case of Escherichia coli diarrhoea in neonatal piglets. Homeopathy. 2010 Jan;99(1):57-62

[iii] Witt CM, Lüdtke R, Baur R, Willich SN. Homeopathic medical practice: long-term results of a cohort study with 3981 patients. BMC Public Health 2005; 5:115

[iv]  Spence DS, Thompson EA, Barron SJ. Homeopathic treatment for chronic disease: a 6-year, university-hospital outpatient observational study. J Altern Complement Med 2005; 11:793–798

[v] Mathie RT, Robinson TW. Outcomes from homeopathic prescribing in medical practice: a prospective, research-targeted, pilot study. Homeopathy 2006; 95:199–205

[vi] Thompson EA, Mathie RT, Baitson ES, et al. Towards standard setting for patient-reported outcomes in the NHS homeopathic hospitals. Homeopathy 2008; 97:114–121

[vii] Witt CM, Lüdtke R, Mengler N, Willich SN. How healthy are chronically ill patients after eight years of homeopathic treatment?–Results from a long term observational study BMC Public Health 2008;8:413

[viii] Rossi E, Endrizzi C, Panozzo MA, Bianchi A, Da Frè M. Homeopathy in the public health system: a seven-year observational study at Lucca Hospital (Italy). Homeopathy 2009; 98:142–148

[ix] Grimaldi-Bensouda L, Abenhaim L, Massol J, et al. EPI3-LA-SER group. Homeopathic medical practice for anxiety and depression in primary care: the EPI3 cohort study. BMC Complement Altern Med. 2016 May 4; 16:125

[x] Kooreman P, Baars EW. Patients whose GP knows complementary medicine tend to have lower costs and live longer. Eur J Health Econ. 2012 Dec;13(6):769-76

[xi] Baars EW, Kooreman P. A 6-year comparative economic evaluation of healthcare costs and mortality rates of Dutch patients from conventional and CAM GPs. BMJ Open. 2014 Aug 27;4(8):e005332

[xii] Colas A, Danno K, Tabar C, Ehreth J, Duru G. Economic impact of homeopathic practice in general medicine in France. Health Econ Rev. 2015;5(1):55

[xiii] Van Wassenhoven M, Galen Y. An observational study of patients receiving homeopathic treatment. Homeopathy 2004 Jan;93(1):3-11

[xiv] Marian F, Joost K, Saini KD, von Ammon K, Thurneysen A, Busato A. Patient satisfaction and side effects in primary care: An observational study comparing homeopathy and conventional medicine. BMC Complement Altern Med. 2008 Sep 18; 8:52

[xv] Witt C, Keil T, Selim D, et al. Outcome and costs of homoeopathic and conventional treatment strategies: a comparative cohort study in patients with chronic disorders. Complement Ther Med. 2005;13(2):79-86

[xvi] Marian F, Joost K, Saini KD, von Ammon K, Thurneysen A, Busato A. Patient satisfaction and side effects in primary care: An observational study comparing homeopathy and conventional medicine. BMC Complement Altern Med. 2008 Sep 18; 8:52

[xvii] Bornhöft G, Wolf U, von Ammon K, Righetti M, Maxion-Bergemann S, Baumgartner S, Thurneysen AE, Matthiessen PF. Effectiveness, safety and cost-effectiveness of homeopathy in general practice – summarized health technology assessment.Forsch Komplementmed. 2006;13 Suppl 2:19-29. Epub 2006 Jun 26. Review

[xviii] Eardley S, Bishop FL, Prescott P, Cardini F, Brinkhaus B, Santos K Ͳ Rey, Vas J, von Ammon K, Hegyi G, Dragan S, Uehleke B, Fønnebø V, Lewith G. CAM use in Europe. The patients’ perspective.Part I: A systematic literature review of CAM prevalence in the EU. 2012. Online retrieved 19-11-2019. https://cam-europe.eu/wp-content/uploads/2018/09/CAMbrella-WP4-part_1final.pdf

[xix] Report of the European Commission, 1997. Online retrieved 15-12-2019 via https://www.hri-research.org/resources/essentialevidence/use-of-homeopathy-across-the-world/

[xx] Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV, Jonas WB. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet. 1997 Sep 20;350(9081):834-4.

[xxi] Cucherat M, Haugh MC, Gooch M, Boissel JP.Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. HMRAG. Homeopathic Medicines Research Advisory Group. Eur J Clin Pharmacol. 2000 Apr;56(1):27-33

[xxii] Hahn RG. Homeopathy: meta-analyses of pooled clinical data. Forsch Komplementmed. 2013;20(5):376-81

[xxiii] Mathie RT, Van Wassenhoven M, Jacobs J et al. Model validity and risk of bias in randomised placebo-controlled trials of individualised homeopathic treatment. Complement Ther Med. 2016 Apr; 25:120-5

[xxiv] Mathie RT, Lloyd, SM, Legg, LA, Clausen J, Moss S, Davidson JR, Ford: Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis. Syst Rev 2014 Dec 6; 3:142

[xxv] Mathie RT, Clausen J. Veterinary homeopathy: systematic review of medical conditions studied by randomised placebo-controlled trials. Vet Rec. 2014 Oct 18;175(15):373-81.

[xxvi] Mathie RT, Clausen J. Veterinary homeopathy: meta-analysis of randomised placebo-controlled trials. Homeopathy. 2015 Jan;104(1):3-8.

[xxvii] Tournier A, Klein SD, Würtenberger S, Wolf U, Baumgartner S. Physicochemical Investigations of Homeopathic Preparations: A Systematic Review and Bibliometric Analysis-Part 2. J Altern Complement Med. 2019 Jul 10

[xxviii] Witt CM, Bluth M, Albrecht H, Weisshuhn TE, Baumgartner S, Willich SN. The in vitro evidence for an effect of high homeopathic potencies–a systematic review of the literature. Complement. Ther Med. 2007 Jun;15(2):128-38

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Did I state above that the manifesto is worth considering in more detail? I need to retract or modify this statement.

Here are the considerations that are relevant, in my view:

  • The statements in the manifesto are based on wishful thinking and do not reflect the reality based on the best evidence available today.
  • The manifesto is the result of a mixture of cherry-picking and/or misinterpreting the evidence.
  • Most of the cited studies have been discussed on this blog in previous posts which disclose their flaws and/or erroneous conclusions.

So, instead of discussing all the tedious details yet again, I will present here a corrected version of the manifesto:

Homeopathy: no solution for major healthcare problems in the EU

  • Does not help to reduce the need of antibiotics in human and veterinary health care, thus reducing the problem of antimicrobial resistance
  • does not increases quality of life and reduces severity of complaints in patients with chronic disease, when integrated in health care
  • Cannot reduce the use of long-term conventional prescription drugs, when integrated in health care

Homeopathy: neither safe nor cost-effective with a high patient satisfaction

  • Cannot lead to lower health care costs, when integrated in health care
  • Is unsafe
  • Patients using homeopathy have no better outcomes than users of conventional treatment, but cause higher costs
  • Quality and correct labelling of homeopathic products is guaranteed by Directive 2001/83 EC

 Some EU consumers expect and demand homeopathy as part of their health care

  • Reported as a much-used complementary medicine in Europe
  • Three out of four European citizens know about homeopathy and out of them many use it for their day-to day health care

 Scientific evidence of the highest calibre fails to confirm the clinical efficacy of homeopathic   medicine

  • Clinical effects of homeopathic medicines have been confirmed by systematic reviews and meta- analyses to be no better than placebo

There is no convincing evidence for biological efficacy of homeopathic medicine

  • No irrefutable scientific evidence has been published on the positive effects of homeopathic products in laboratory settings

During my almost 30 years of research into so-called alternative medicine (SCAM), I have published many papers which must have been severe disappointments to those who advocate SCAM or earn their living through it. Many SCAM proponents thus reacted with open hostility. Others tried to find flaws in those articles which they found most upsetting with a view of discrediting my work. The 2012 article entitled ‘A Replication of the Study ‘Adverse Effects of Spinal Manipulation: A Systematic Review‘ by the Australian chiropractor, Peter Tuchin, seems to be an example of the latter phenomenon (used recently by Jens Behnke in an attempt to defame me).

Here is the abstract of the Tuchin paper:

Objective: To assess the significance of adverse events after spinal manipulation therapy (SMT) by replicating and critically reviewing a paper commonly cited when reviewing adverse events of SMT as reported by Ernst (J Roy Soc Med 100:330-338, 2007).

Method: Replication of a 2007 Ernst paper to compare the details recorded in this paper to the original source material. Specific items that were assessed included the time lapse between treatment and the adverse event, and the recording of other significant risk factors such as diabetes, hyperhomocysteinemia, use of oral contraceptive pill, any history of hypertension, atherosclerosis and migraine.

Results: The review of the 32 papers discussed by Ernst found numerous errors or inconsistencies from the original case reports and case series. These errors included alteration of the age or sex of the patient, and omission or misrepresentation of the long term response of the patient to the adverse event. Other errors included incorrectly assigning spinal manipulation therapy (SMT) as chiropractic treatment when it had been reported in the original paper as delivered by a non-chiropractic provider (e.g. Physician).The original case reports often omitted to record the time lapse between treatment and the adverse event, and other significant clinical or risk factors. The country of origin of the original paper was also overlooked, which is significant as chiropractic is not legislated in many countries. In 21 of the cases reported by Ernst to be chiropractic treatment, 11 were from countries where chiropractic is not legislated.

Conclusion: The number of errors or omissions in the 2007 Ernst paper, reduce the validity of the study and the reported conclusions. The omissions of potential risk factors and the timeline between the adverse event and SMT could be significant confounding factors. Greater care is also needed to distinguish between chiropractors and other health practitioners when reviewing the application of SMT and related adverse effects.

The author of this ‘replication study’ claims to have identified several errors in my 2007 review of adverse effects of spinal manipulation. Here is the abstract of my article:

Objective: To identify adverse effects of spinal manipulation.

Design: Systematic review of papers published since 2001.

Setting: Six electronic databases.

Main outcome measures: Reports of adverse effects published between January 2001 and June 2006. There were no restrictions according to language of publication or research design of the reports.

Results: The searches identified 32 case reports, four case series, two prospective series, three case-control studies and three surveys. In case reports or case series, more than 200 patients were suspected to have been seriously harmed. The most common serious adverse effects were due to vertebral artery dissections. The two prospective reports suggested that relatively mild adverse effects occur in 30% to 61% of all patients. The case-control studies suggested a causal relationship between spinal manipulation and the adverse effect. The survey data indicated that even serious adverse effects are rarely reported in the medical literature.

Conclusions: Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation.

In my view, there are several things that are strange here:

  1. Tuchin published his paper 5 years after mine.
  2. He did not publish it in the same journal as my original, but in an obscure chiro journal that hardly any non-chiropractor would ever read.
  3. Tuchin never contacted me and never alerted me to his publication.
  4. The journal that Tuchin chose was not Medline-listed in 2012; consequently, I never got to know about the Tuchin article in a timely fashion. (Therefore, I did never respond to it.)
  5. A ‘replication study’ is a study that repeats the methodology of a previous study.
  6. Tuchin’s paper is therefore NOT a replication study. Firstly, mine was a review and not a study. Secondly, and crucially, Tuchin never repeated my methodology but used an entirely different one.

But arguably, these points are trivial. They should not distract from the fact that I might have made mistakes. So, let’s look at the substance of Tuchin’s claim, namely that I made errors or omissions in my review.

As to ‘omissions’, one could argue that a review such as mine will always have to omit some details in order to generate a concise summary. The only way to not omit any details is to re-publish all the primary papers in one large volume. Yet, this can hardly be the purpose of a systematic review.

As to the ‘errors’, it seems that the ages and sex of three patients were wrong (I have not checked this against the primary publications but, for the moment, I believe Tuchin). This is, of course, lamentable and – even though I have no idea whether the errors happened at the data extraction phase, during the typing, the revising, or the publishing of the paper – it is entirely my responsibility. I also seem to have mistaken a non-chiropractor for a chiropractor. This too is regrettable but, as the review was about spinal manipulation and not about chiropractic, the error is perhaps not so grave.

Be that as it may, these errors are unquestionably not good, and I can only apologise for them. If Tuchin had dealt with them in the usual way – by publishing in a timely fashion a ‘letter to the editor’ of the JRSM – I could have easily corrected them for everyone to see.

But I think there is a more important point to be made here:

Tuchin concludes his paper stating that it is unwise to make conclusions regarding causality from any case study or multiple case studies. The number of errors or omissions in the 2007 Ernst paper significantly limit any reported conclusions. I believe that both sentences are unjustified. The safety of any intervention in routine use has to be examined on the basis of published case studies. This is particularly true for chiropractic where no post-marketing surveillance similar to that for drugs exists.

The conclusions based on such evidence can, of course, never be firm, but they provide valuable signals that can prompt more rigorous investigations in the interest of patient safety. In view of such considerations, my own conclusions in my 2007 paper were, I think, correct and are NOT invalidated by my relatively trivial mistakes: spinal manipulation, particularly when performed on the upper spine, has repeatedly been associated with serious adverse events. Currently the incidence of such events is unknown. Adherence to informed consent, which currently seems less than rigorous, should therefore be mandatory to all therapists using this treatment. Considering that spinal manipulation is used mostly for self-limiting conditions and that its effectiveness is not well established, we should adopt a cautious attitude towards using it in routine health care. 

And my conclusions in the abstract have now, I believe, become established wisdom. They are thus even less in jeopardy through my calamitous lapsus or Tuchin’s ‘replication study’: Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation. 

 

 

Functional Neurology (FN) is an approach used by some chiropractors. One website proudly proclaims that Functional Neurology, sometimes referred to as Chiropractic Neurology, is a term used to describe a variety of evidence-based treatments relating to neurological disorders. And another one informs us that Functional neurology, aka chiropractic neurology, is a healthcare discipline that utilizes neuroplasticity and contemporary clinical neuroscience to both evaluate and rehabilitate patients that suffer from a complex neurological condition or simply want to optimize their performance. A comprehensive neurological examination is performed in order to determine which area of the nervous system is not functioning appropriately. A customized therapy program is then tailored to address each person’s individualized neurological dysfunction.

The specific therapeutic claims that are being made for FN by chiropractors are impressive. The following list is a non-exhaustive attempt to document some of the conditions which functional neurologists claim to be able to treat: ADD/ADHD, Alzheimer’s, Anxiety disorders, Asperger’s Syndrome, Autism, Balance disorders, Blackouts, Blindness, Brain Aging issues, Canal stenosis, Cerebellar disorders,Chronic pain disorders, Cervical myelopathy, Coma, Complex regional pain syndromes, Concentration issues, Depression, Diplopia, Dizziness, Double vision, Dyslexia, Dystonia, Epilepsy, Fainting, Headaches, Heart arrhythmias, Irritable bowel syndrome, Learning difficulties, Memory issues, Mental Health, Migraines, Motion sickness, Movement disorders, Multiple sclerosis, Neglect syndromes, Numbness, Parkinson’s disease, Peripheral neuropathies, Radicular/nerve root conditions, Reflex sympathetic dystrophy, Sexual dysfunction, Sleep apnea, Sleep problems, Snoring, Speech problems, Spinal cord compression, Squints/skew deviations of the eyes, Strokes, Syncope, Tinnitus, Tics, Tourette’s, Tremors, Vertigo and Visual disturbances.

Is any of this backed up by evidence?

A review of FN included 9 articles. The included studies were conducted on adults or children, symptomatic or not, and investigated various interventions consisting of single or multiple stimuli, of varied nature, all primarily said to be provided to stimulate brain areas. Conditions included attention deficit disorders, attention deficit and hyperactivity disorders, autism-spectrum disorders, cortical visual impairment, traumatic brain injury, and migraine. Balance and the “blind spot” were investigated in healthy subjects. Major design and methodological issues were identified in all 9 studies; only 4 were considered as (potentially) appropriate for further scrutiny.

The authors concluded that no robust evidence could be found in relation to the effect or benefit of the tested FN interventions.

In a nutshell: FN is yet another addition to chiro-quackery.

Dr Jens Behnke has attracted my attention several times before (most recently here and here). Today I have decided to admit him into my ‘ALTERNATIVE MEDICINE HALL OF FAME’.

He finds himself in the company of giants:

John Weeks (editor of JCAM)

Deepak Chopra (US entrepreneur)

Cheryl Hawk (US chiropractor)

David Peters (osteopathy, homeopathy, UK)

Nicola Robinson (TCM, UK)

Peter Fisher (homeopathy, UK)

Simon Mills (herbal medicine, UK)

Gustav Dobos (various, Germany)

Claudia Witt (homeopathy, Germany and Switzerland)

George Lewith (acupuncture, UK)

John Licciardone (osteopathy, US)

Why does Behnke deserve this honour?

Because, 4 years ago, he made his doctorate under the supervision of Prof Harald Walach, pseudoscientist of the year 2012 and proven teller of falsehoods?

No, there are better reasons.

On Twitter, Behnke describes himself as a research consultant for homeopathy at the Karl and Veronica Carstens-Foundation: Evidence based medicine, CAM, clinical and basic research, health. The Carstens Stiftung say he is ‘programme director integrative medicine’. On facebook, he is merely ‘ ‘Referent of  ‘Redaktion Natur und Medizin’. And on ‘Research Gate’ he lists 12 areas of skills and expertise:

Evidence Based Medicine
Medical & Health Profession Education
Meta-Analysis
Observational Studies
Science Communication
Social Media
Randomized Control Trials
Clinical Research
Philosophy Of Science
Complementary & Alternative Medicine
Integrative Medicine
Homeopathy

If this is not impressive, I don’t know what is! Particularly, if one knows that he is not a medical doctor at all!!!

So, let’s look at the list to decide whether he deserves the honour of becoming a member of my ‘HALL OF FAME’. Specifically, let’s check how many Medline-listed articles he has to his name in each of the above areas:

Evidence Based Medicine = 0
Medical & Health Profession Education = 0
Meta-Analysis = 0
Observational Studies = 0
Science Communication = 0
Social Media = 0
Randomized Control Trials = 0
Clinical Research = 0
Philosophy Of Science = 0
Complementary & Alternative Medicine = 0e
Integrative Medicine = 0
Homeopathy = 0

(No, you don’t need to praise me for my detailed, time-consuming research. It was not difficult and very quick: Jens Behnke, the ‘research consultant, has precisely zero Medline-listed publications).
So has Behnke ever conducted:

  • a meta-analysis? No
  • an observational study? I don’t think so
  • a randomised trial? No
  • any other clinical research? No

In the past, I tended to admit to my HALL OF FAME mainly those SCAM researchers who had published plenty of papers but had no study to their name that drew a negative conclusion. Behnke is not in that league. He is nevertheless worthy for his highly elaborate concept. Remember, he is a ‘research consultant in homeopathy’, and homeopathy obeys different rules than any other form of quackery. One of its axioms holds that LESS IS MORE. And considering this principle, Behnke surely must be THE expert! No publication, in homeopathic logic, evidently means that he is better than anyone else.

So, a warm welcome to our new member Jens Behnke: MAY YOUR UNPRODUCTIVITY AS A EXPERT IN 12 DIFFERENT FIELDS OF INQUIRY LAST FOR MANY MORE YEARS!

And congratulations also to the Carstens Stiftung who have so far spent 36 000 000 Euro on SCAM-research and pay Behnke’s salary as ‘research consultant’: I am sure you guys deserve him!

PS

In case Dr Behnke reads this: it is an internationally accepted standard of honesty and transparency that someone who has a doctor title and works in or comments on medical matters makes it clear that he/she is not medically trained or experienced, that in fact he/she is not a medical doctor. If not, one might think that this person is deliberately trying to mislead the public.

It seems that some people are pushing the notion that Boiron’s homeopathic product

Oscillococcinum®

might be helpful for the prevention and/or treatment of the Corona virus infection. To get an idea how implausible this assumption is, read my previous post on the subject.

The website of Boiron, the producer of the product, seems undeterred by plausibility and states the following:

Clinical studies show Boiron Oscillococcinum (Oscillo®) reduces the duration and severity of flu-like symptoms when taken at the onset of symptoms.1-2 Oscillo does not cause drowsiness and has no known or reported drug interactions.

Uses*

  • Temporarily relieves flu-like symptoms such as body aches, headache, fever, chills and fatigue
  • Non-drowsy; no drug interactions
  • Easy-to-take, quick-dissolving pellets
  • For everyone 2 years of age and older
  • Make sure your patients always have Oscillococcinum on hand—it works best when taken at the first sign of symptoms. Help your patients feel better before they feel worse.

While this text does not state that Oscillococcinum works for the coronavirus, one could easily read it as implying it, particularly if one also considers this tweet:

Oscillococcinum USA
@OscilloUSA
Getting sick when travelling can ruin the best of vacations. Take non-drowsy Oscillococcinum the moment you feel body aches, headache, fever, chills or fatigue coming on. http://bit.ly/2BGCmCz
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On the Internet we find many much more direct claims. Take this website, for instance:

The commonly indicated Homeopathic remedies for Coronavirus are: –
• OSCILLOCOCCINUM
• Arsenic Album
• INFLUENZINUM

**However, for best results contact a Qualified Homeopathic doctor so that correct medicines can be prescribed.

And even some politicians promote such irresponsible nonsense.

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All the claims about Oscillococcinum have one thing in common: they are not evidence based! Any notion that it might work against the coronavirus is pure fantasy. And the above statement by Boiron is based on two cherry-picked studies. The totality of the evidence, however, does not show that Oscillococcinum is effective. The current Cochrane review says about its effectiveness: There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum(®) in the prevention or treatment of influenza and influenza-like illness. Our findings do not rule out the possibility that Oscillococcinum(®) could have a clinically useful treatment effect but, given the low quality of the eligible studies, the evidence is not compelling. There was no evidence of clinically important harms due to Oscillococcinum(®).

The reason, I guess, why this conclusion is not more forthright stating THERE IS NO GOOD EVIDENCE THAT OSCILLOCOCCINUM HAS ANY EFFECT can be found in the list of conflicts of interest of the paper’s authors:

All three review authors are research‐active in the field of homeopathy. They were members of the International Scientific Committee for Homeopathic Investigations (ISCHI), whose membership also included two employees of Boiron (the manufacturers of Oscillococcinum®), and whose committee activities ceased in July 2013. Progress with the Cochrane Review on Oscillococcinum® was presented briefly at ISCHI meetings in 2010 and 2011. The drafting of this Cochrane Review was carried out independently of those communications and of the authors’ other ongoing research activity. ISCHI has not run or sponsored any research on Oscillococcinum®.

Robert T Mathie: Dr Mathie is Research Development Adviser, British Homeopathic Association. He was a member of the International Scientific Committee on Homeopathic Investigations, which ceased its committee activities in July 2013. Joyce Frye: Part of Dr Frye’s salary was supported by a research grant from the Standard Homeopathic Company, paid to her employer, the Center for Integrative Medicine, Department of Family Medicine, University of Maryland, USA. Support ended in June 2013 when Dr Frye resigned from the University of Maryland. Standard Homeopathic Company does not manufacture Oscillococcinum or any similar product, and had no interest in the outcome of the review. Dr Frye received honoraria from the International Scientific Committee on Homeopathic Investigations, which was dissolved in July 2013. Peter Fisher: I am Expert Adviser on Complementary and Alternative Medicine to the National Institute for Health and Clinical Excellence (NICE), which may take an interest in the evidence in this review. I am Editor in Chief of an international, peer‐reviewed journal dedicated to homeopathy. All payments and reimbursements for lectures have been from universities or professional or learned societies. None of these lectures has been dedicated to the subject of this review. Some meetings have been supported by grants from commercial interests, including the manufacturer of the product that is the subject of the review.

So, to be clear: oscillococcinum does not help against the corona or any other virus. Those who claim otherwise are either mistaken, or have a commercial interest, or both.

A team of chiropractic researchers conducted a review of the safety of spinal manipulative therapy (SMT) in children under 10 years. They aimed to:

1) describe adverse events;

2) report the incidence of adverse events;

3) determine whether SMT increases the risk of adverse events compared to other interventions.

They searched MEDLINE, CINAHL, and Index to Chiropractic Literature from January 1, 1990 to August 1, 2019. Eligible studies were case reports/series, cohort studies and randomized controlled trials. Studies of high and acceptable methodological quality were included.

Most adverse events are mild (e.g., increased crying, soreness). One case report describes a severe adverse event (rib fracture in a 21-day-old) and another an indirect harm in a 4-month-old. The incidence of mild adverse events ranges from 0.3% (95% CI: 0.06, 1.82) to 22.22% (95% CI: 6.32, 54.74). Whether SMT increases the risk of adverse events in children is unknown.

The authors concluded that the risk of moderate and severe adverse events is unknown in children treated with SMT. It is unclear whether SMT increases the risk of adverse events in children < 10 years.

Thanks to their ingenious methodology, the authors managed to miss 11 of the 13 studies included in the review by Vohra et al which reported 9 serious adverse events and 20 cases of delayed diagnosis associated with SMT. Another review reported 15 serious adverse events and 775 mild to moderate adverse events following manual therapy. As far as I can see, the authors of the new review make just one reasonable point:

We recommend the implementation of a population-based active surveillance program to measure the incidence of severe and serious adverse events following SMT treatment in this population.

In the absence of such a surveillance system, any incidence figures are not just guess-work but also a depiction of the tip of a much bigger iceberg. So, why do the authors of this review not make this point clearly and powerfully? Why does the review read mostly like an attempt to white-wash a thorny subject? Why do they not provide a breakdown of the adverse events according to profession? The answer to these questions can be found at the very end of the paper:

This study was supported by the College of Chiropractors of British Columbia to Ontario Tech University. The College of Chiropractors of British Columbia was not involved in the design, conduct or interpretation of the research that informed the research. This research was undertaken, in part, thanks to funding from the Canada Research Chairs program to Pierre Côté who holds the Canada Research Chair in Disability Prevention and Rehabilitation at Ontario Tech University, and from the Canadian Chiropractic Research Foundation to Carol Cancelliere who holds a Research Chair in Knowledge Translation in the Faculty of Health Sciences at Ontario Tech University.

This study was supported by the College of Chiropractors of British Columbia to Ontario Tech University. The College of Chiropractors of British Columbia was not involved in the design, conduct or interpretation of the research that informed the research. This research was undertaken, in part, thanks to funding from the Canada Research Chairs program to Pierre Côté who holds the Canada Research Chair in Disability Prevention and Rehabilitation at Ontario Tech University, and funding from the Canadian Chiropractic Research Foundation to Carol Cancelliere who holds a Research Chair in Knowledge Translation in the Faculty of Health Sciences at Ontario Tech University.

I have often felt that chiropractic is similar to a cult. An investigation by cult members into the dealings of a cult is not the most productive of concepts, I guess.

Many chiropractors claim that spinal manipulation (SM) has an effect on the pain threshold even in asymptomatic subjects, but SM has never been compared in studies to a validated sham procedure. Now a chiropractic research team has published a study investigating the effect of SM on the pressure pain threshold (PPT) when measured in

i) the area of intervention,  

ii) an area remote from the intervention.

In addition, the researchers measured the size and duration of the effect.

In this randomized cross-over trial, 50 asymptomatic chiropractic students had their PPT measured at baseline, immediately after and every 12 min after intervention, over a period of 45 min, comparing values after SM and a previously validated sham. The trial was conducted during two sessions, separated by 48 h. PPT was measured both regionally and remotely from the ‘treated’ thoracic segment. Blinding of study subjects was tested with a post-intervention questionnaire.

The results show that the study subjects had been successfully blinded. No statistically significant differences were found between SM and sham estimates, at any time or anatomical location.

The authors concluded that, when compared to a valid sham procedure and with successfully blinded subjects, there is no regional or remote effect of spinal manipulation of the thoracic spine on the pressure pain threshold in a young pain-free population.

Reduced pain sensitivity following SM (often also called ‘manipulation-induced hypoalgesia’ (MIH)) turns out to be little more than a myth promoted by chiropractors for the obvious reason of boosting their business (6 further myths are summarised in the over-optimistic chiropractic advertisement above).

A recent review of the evidence found that systemic MIH (for pressure pain threshold) does occur in musculoskeletal pain populations, though there was low quality evidence of no significant difference compared to sham manipulation. Future research should focus on the clinical relevance of MIH, and different types of quantitative sensory tests.

An enthusiast of homeopathy recently posted an overview of systematic reviews of homeopathy concluding that the data we do have point towards homeopathy as having an effect greater than that of placebo:

In recent decades, homeopathy has been examined via a number of clinical trials, the number of which now allow meta-analysis. As we can see from the study findings, the type of homeopathy research (ie, individualized vs non-individualized, placebo-controlled vs non-placebo-controlled) can have a strong influence on the results, although trial quality also has a strong effect.

All meta-analyses performed in at least a somewhat open and rigorous manner have found statistically significant effects. This suggests that homeopathy has a greater-than-placebo effect, or at least a strong trend in that direction, when using data from the totality of homeopathy research, or from individualized, placebo-controlled trials. The meta-analyses with questionable methodology, one of which is undergoing government investigation for academic irregularities, have produced negative results, which have been demonstrated to be a direct result of their exclusion of vast swathes of the homeopathic clinical trial literature (based on arbitrary and unexplained criteria), as well as of their failure to differentiate – as Mathie has done – different types of homeopathic research.

The clinical data are flawed. Issues with methodology used in homeopathy RCTs, combined with a lack of research funding, have produced a lack of high-quality trials and data. However, the data we do have point towards homeopathy as having an effect greater than that of placebo.

There can be no argument with this conclusion, aside from possible new data emerging. Anyone who disputes this is going against the existing set of the highest-quality evidence on homeopathy.

His overview is based on the following publications:

Kleijnen, 19911 All types of homeopathy (eg, single remedy vs combination). Methodological quality assessed; 105 trials. Results: Positive trend, regardless of type of homeopathy; 81 trials were positive, 24 showed no effect.
Linde, 19972 All types of homeopathy. Out of 185 trials, 119 met inclusion criteria; 89 of these had extractable data. Results: OR = 2.45 (95% CI 2.05-2.93).
Ernst, 19983 Individualized homeopathy; 5 trials determined to be high-quality. Results: OR = 0.
Linde, 19985 Individualized homeopathy; 32 trials, 19 of which had extractable data. Results: OR = 1.62 for all trials (95% CI 1.17-2.23). Only high-quality trials produced no significant trend.
Cucherat, 20009 All types of homeopathy; 118 trials, 16 of which met inclusion criteria. Used unusual method of combining p values. Results: All trials = p< 0.000036. Less than 10% dropouts: p<0.084; less than 5% dropouts (higher standards than most trials considered reliable): p<0.08 (non-significant).
Shang, 200511 All types of homeopathy; only 8 trials selected from 21 high-quality trials of 110 selected with unusual criteria. Results: OR = 0.88 (0.65-1.19). Result strongly disputed by statisticians.
Mathie, 201413 Individualized homeopathy; of the analysis pooled data from 22 higher-quality, individualized, double-blind RCTs. Results: OR = 1.53 (1.22-1.91) for all trials pooled; OR = 1.93 (1.16-3.38) for the 3 reliable trials.
NHMRC, 201516 Out of 176 studies, 171 were excluded, leaving only 5 for the study. Investigators used unprecedented methods, did not combine data, and are currently under investigation for outcome shopping. Results: Negative results.
Mathie, 201720 Non-individualized homeopathy; very few higher-quality trials. Results: For 54 trials with extractable data, SMD = -0.33 (-0.44, -0.21). When these were adjusted for publication bias, SMD = -0.16 (-0.46,-0.09). The 3 high-quality trials had non-significant results: SMD = -0.18 (-0.46, +0.09).
Mathie, 201821 Individualized, other-than-placebo-controlled trials; 11 trials found, 8 with extractable data. Results: 4 heterogeneous comparative trials showed a non-significant difference. One trial in this group was positive. Three heterogeneous trials with additive homeopathy showed a statistically significant SMD. No definitive conclusion possible due to trial heterogeneity, poor quality, and low number of trials.
Mathie, 201922 Non-individualized, other-than-placebo-controlled trials; 17 RCTs found, 14 with high risk of bias. Results: Significant heterogeneity prevented much comparison; 3 comparable trials showed a non-significant SMD.

Apart from getting the wrong end of the stick when interpreting the results of these papers (see for instance here, and here), there are other rather embarrassing flaws in this overview:

  1. Many older systematic reviews were omitted (including about 10 of my own papers). This is relevant because the author of the above review went beck until 1991 to find the reviews he included.
  2. Several new papers were missing as well. This is relevant because the author evidently included reviews up to 2019. Here are the key passages from the conclusions of some of them:

homoeopathy as a whole may be considered as a placebo treatment.

We tested whether p-curve accurately rejects the evidential value of significant results obtained in placebo-controlled clinical trials of homeopathic ultramolecular dilutions. Our results suggest that p-curve can accurately detect when sets of statistically significant results lack evidential value.

We found no evidence to support the efficacy of homeopathic medicinal products

no firm conclusions regarding the effectiveness and safety of homeopathy for the treatment of IBS can be drawn.

Due to both qualitative and quantitative inadequacies, proofs supporting individualized homeopathy remained inconclusive.

… the use of homeopathy currently cannot claim to have sufficient prognostic validity where efficacy is concerned.

I am, of course, not saying that this overview amounts to anything like a systematic review. It merely gives you a flavour how trustworthy proponents of homeopathy are when they pretend to provide us with an objective evaluation of the best available evidence.

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