The Evidence Base for Homeopathy

In July 2019, I gave a talk about the Evidence Base for Homeopathy to staff at Brighton Health and Wellbeing Centre. Here is a transcript, for those who would like to delve a little more deeply into the science.

The Evidence Base for Homeopathy – a talk for healthcare professionals
Dr Jessica Robinson

What information do you need to have about a medicine or group of medicines in order to decide whether or not to prescribe it to your patients?
2. Is this biological activity CLINICALLY SIGNIFICANT/ DOES IT WORK?
3. How SAFE IS IT?
4. Does it cause SIDE EFFECTS?
5. Does it INTERACT ADVERSELY with other medications?
6. Is it ACCEPTABLE to patients?
7. Is it COST EFFECTIVE? CAN WE AFFORD IT? (Can we afford not to use it?)

There are other interesting questions, such as
8. How does it exert its effect?
9. Does this fit with our current scientific understanding of things?

These are important questions to consider, but perhaps of secondary importance to clinicians. Throughout the history of medicine, there have been many occasions when medicines have been prescribed whose mode of action has been a mystery.
If a medicine can be shown clearly to fulfil the first set of criteria in rigourous scientific studies, but its actions are not predicted by current scientific theories, then those theories must be inadequate. Is it right to deny someone a safe, effective, cost-effective treatment just because we don’t understand how it works?

Where experiments defy “common sense” and “conventional wisdom”

There is a famous experiment, originally described by Richard Feynman, in which a beam of individual electrons is fired at a screen with two slits in it to a photo-reactive screen beyond. Conventional wisdom would say that two lines of light would form on the photo-reactive screen, where the electrons from each slit land.
In reality, what happens is that a series of lines of light are seen on the screen; an interference pattern, as if the discreet particles were combining to behave as a wave.
The physicists conducting this experiment wondered how on earth this could be, so they put a camera/detector into the set-up to observe how often an electron went through each of the slits.
The result?
The predicted number of electrons went through each slit. What was unexpected was that, with the observing detector in place, only two lines of light formed.
If this experiment is repeated again, leaving the detector in place but unplugging it, the interference pattern returns.
As far as I am aware, no-one has yet been able to explain this. But absence of an explanation does not negate the results, which are highly reproducible. Computer technology relies on this peculiar effect of electrons, even though no-one knows how it works.

Similarly, when you fire gamma rays at substances suspended in solutions in heavy water (D2O) that are frozen to 70K and then warmed to 220K, light is emitted. The pattern of light emitted is characteristic for each solute. Let us take the example of lithium chloride. A solution of lithium chloride in heavy water (D2O) gives a light pattern which is characteristic of lithium chloride.
If you then repeat the experiment with a solution of lithium chloride which has been homeopathically diluted; that is to say, diluted and vigourously shaken, or “succussed”, with each successive dilution, until it is well beyond Avogadro’s constant, an ultramolecular solution, you get exactly the same pattern of light emission from the sample as you would from the original solution. Sceptics say there is nothing left in homeopathic solutions, but something must be there to be able to emit photons of light characteristic of lithium chloride.
• Rey L. Thermoluminescence of ultra-high dilutions of lithium chloride and sodium chloride. Physica A, 2003; 323: 67–74.

How can something be “diluted out of existence” and still leave a signal?
Some suggested answers have emerged from work on nanoparticles. Nanoparticles can form in many different circumstances, either by being constructed from individual atoms and molecules, or by the destruction of a larger substance. Nanoparticles have been shown to form in homeopathic dilutions, firstly using suspensions of metals such as gold and copper, diluted to 30c and 200c (equivalent to 10 to the power -60 and 10 to the power of -400 respectively). They were demonstrated by the use of transmission electron microscopy, electron diffraction and plasma-atomic emission spectroscopy.
• Chikramane PS, Suresh AK, Bellare JR, Kane SG: Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Homeopathy 2010, 99(4):231–242).

It is postulated that these nanoparticles may have a coating of silica, derived from the glassware. Whatever their ultimate form proves to be, somehow they carry the signal of the original substance diluted. Work by Iris Bell looked at the stability of the nanoparticles and found that the more they are succussed, the more stable they appear to be.
• Bell, I and Schwartz, G: Enhancement of adaptive biological effects by nanotechnology preparation methods in homeopathic medicines. Homeopathy (2015) 104, 123-138.

Can homeopathically-diluted substances exert a biological effect?
If wheat seeds are stressed, they exude a liquid. If this evaporates, it leaves crystallised remnants which have a clearly identifiable, reproducible structure. If the wheat seeds are treated with homeopathic Zinc at 30c potency (10 to the power -60), the polycrystalline structure does not form.
• Kokornaczyk, M et al. Homeopathy (2016) 105, 173-179 Polycrystalline structures formed in evaporating droplets as a parameter to test the action of Zincum Metallicum 30c in a wheat seed model.

More interestingly, in terms of clinical potential, are experiments on cell lines of macrophages. Paolo Bellavite’s lab in Verona used PCR quantitation to look at gene expression in human macrophages treated with ultramolecular dilutions of Arnica Montana compared to control and found enormously statistically significant changes in gene regulation, specifically in the areas of neutrophil recruitment and angiogenesis.
• Olioso, D et al. Homeopathy (2016) 105, 131-147: Arnica Montana effects on gene expression in a human macrophage cell line. Evaluation by quantitative Real-Time PCR.

In mice macrophages treated with a combination homeopathic remedy, Canova, the remedy led to differential gene expression in 147 genes compared to control.
• Carolina Carmargo de Oliveira et al. J. Cell Biochem. 104: 1364-77, 2008. Gene expression profiling of macrophages following mice treatment with an immunomodulator medication.

Does this activity translate into noticeable biological effects?
When tadpoles have thyroxine added to their water, it increases their metabolic rate such that they develop faster. If ultramolecular homeopathic dilutions of thyroxine are added to this mixture, the effects of the thyroxine are blocked. (Worryingly, placing the homeopathic thyroxine near a mobile phone inactivated it so that it no longer blocked the action of thyroxine).
• Weber S, Endler PC, Welles SU et al. The effect of homeopathically prepared thyroxine on highland frogs. Homeopathy, Volume 97, Issue 3, July 2008, Page 165)

Mice are anxious animals. If given the choice between a dark chamber and a light one, the mouse will tend to stay much longer in the dark. This forms the basis for experiments of treatments of anxiety in mice, in the form of the Light/Dark test. Mice have access to two rooms, one light and one dark. The amount of time they choose to spend in the dark room is assumed to represent their level of anxiety. If they are given placebo, they spend most of their time in the dark, and explore little. If you treat them with anxiolytic Buspirone, they spend more time in the light and explore more. If instead you treat them with homeopathic Gelsemium, they also spend more time in the lit area and more time exploring. This is a highly statistically significant effect and applies at a variety of dilutions; the greatest effect was at a 9c and a 30c dilution, and this was significantly greater than the effect of the pharmaceutical agent Buspirone.
• Magnani, P et al. Psychopharmacology (2010) 210: 533-545. Dose effect study of Gelsemium sempervivens in high dilutions on anxiety-related responses in mice.

Is this biological activity clinically significant?
Detractors of homeopathy say there is no evidence that homeopathy is useful for any medical condition. As of August 2017, there have been 1137 clinical trials of homeopathy, including 489 randomised controlled trials, 534 trials of homeopathy versus placebo and 174 trials of homeopathy versus standard treatment. Reviewing all these studies, 41% were positive for homeopathy; 54% were inconclusive (insufficiently powered) and 5% were negative. This is remarkably similar to the studies of conventional medicines, which show 44% positive, 49% inconclusive and 7% negative results.
A systematic review was carried out in 2014 by Robert Mathie. He looked at 32 RCTs of homeopathy used in 24 different medical conditions. He found that 22 trials were analysable and all showed positive results for homeopathy. The three most reliable studies had an odds ratio of 1.98, with 95% confidence intervals of 1.16 – 3.38. He did a funnel plot of all the studies, plotting the quality of the study against the odd ratio. Generally, in most systematic reviews, the funnel plot shows falling odds ratio as the study quality increases (indicating that the likelihood that the intervention is responsible for any improvement decreases as the methodology of the study improves). In this case, the funnel plot showed the opposite: as the quality of the methodology of the study improved, the odds ratio increased. The most rigourous studies of homeopathy show a greater, not lesser effect of homeopathy.
• Mathie RT, Lloyd SM, Legg LA, et al. Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis. Syst Rev 2014;3:142

Some examples:
In 2000, David Reilly published a study in the BMJ of homeopathy versus placebo for allergy. There were four RCTs in the study: two for hay fever, one for allergic asthma and one for perennial rhinitis. 250 patients were involved in the trial and they were treated with 30c dilutions (10-60) of the allergen thought to cause the symptoms. The results were dramatically positive for homeopathy with a p value of 0.0007 (95% confidence interval of 4.2-15.4).
• Taylor MA, Reilly D, Llewellyn-Jones RH, et al. Randomized controlled trials of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. British Medical Journal, 2000; 321: 471–476

In 2001, Heiner Frei published a study of 230 children treated for acute otitis media at the University Paediatric Clinic in Berne. The protocol was that each child would be assessed and then given a homeopathic remedy. If they were not pain-free after 6 hours, they were then given a second remedy. If they were not pain-free at 12 hours, they were treated with antibiotics. 39% of children were pain-free at 6 hours. A further 33% were pain free at 12 hours. Therefore, only 28% required antibiotics. The resolution of symptoms was 2 ½ times faster than in a comparable series of children treated only with antibiotics. There was a 14% cost saving using homeopathy.
• Frei, H and Thurneysen, A. British Homeopathic Journal 2001 (90), 180-182. Homeopathy in acute otitis media in children: Treatment effect or spontaneous resolution?

Comparative effectiveness with conventional treatments:
Two large studies, carried out 6 years apart, compared the use of homeopathy versus conventional antibiotic treatment of patients with acute respiratory problems. Response to treatment was assessed at 14 days: 82.6% had recovered with homeopathy compared to 68% with conventional treatment.
• Riley D, Fischer M, Singh B, et al. (2001). Homeopathy and Conventional Medicine: An Outcomes Study Comparing Effectiveness in a Primary Care Setting. Journal of Alternative and Complementary Medicine, 7:149–159
• Haidvogl M Riley D, Heger M et al. Homeopathic and conventional treatment for acute respiratory and ear complaints: A comparative study on outcome in the primary care setting. BMC Complement Altern Med. 2007; 7: 7

Safety of Homeopathy
A systematic review of the safety of homeopathy in 2000 concluded that homeopathy was generally safe; it could provoke adverse effects but these were generally very mild and transient. There were very few reports of side effects. Significant adverse effects that had been reported were commonly from herbal remedies wrongly described as homeopathic. The main risks were due to the prescriber rather than the medicine.
• Dantas F, Rampes H (2000). Do homeopathic medicines provoke adverse effects? A systematic review. Br Homeopath J. 89:S35–38.

As for interaction between homeopathic and conventional medicines, I have not been able to find any significant evidence. A google search of homeopathy drug interactions reveals nothing except the frequent confusion between homeopathy and herbal medicine (which, by contrast, can interact adversely with conventional medicines).

Is homeopathy acceptable to patients?
Homeopathy is used by an estimated five hundred million people worldwide. Many of your patients will use homeopathy. Two surveys in the UK estimated that between 3 and 10% of the population of the UK used homeopathy each year. In France, where homeopathy is more integrated into the health system and a significant proportion of GPs are trained homeopaths, 10% of the population use it annually, rising to 18% among those under 4 years of age.
• Relton, C, Cooper, K, Viksveen, P, Fibert, P, Thomas, K. Prevalence of homeopathy use by the general population worldwide: a systematic review. Homeopathy. 2017; 106: 69–78

Studies of the demographics of people who choose homeopathy consistently show that it is used by people who are more likely to be health conscious and to have a college/university education. It is perceived by these people as very helpful.
• Lert F, Grimaldi-Bensouda L, Rouillon F et al. Characteristics of patients consulting their regular primary care physician according to their prescribing preferences for homeopathy and complementary medicine. Homeopathy (2014);103: 51-57

Outcome studies from the homeopathic hospitals in the UK show that 70% of patients report that they have benefitted from homeopathy. Given that no-one at present in the UK can get a referral to the homeopathic hospitals unless they have failed to respond to conventional options, this is remarkable.
• Spence DS, Thompson EA, Barron SJ. Homeopathic treatment for chronic disease: a 6-year university-hospital outpatient observational study. Journal of Alternative and Complementary Medicine, 2005; 5: 793–798

Is it cost-effective (can we afford not to use it?)
There have been a number of cohort studies comparing homeopathic treatment with conventional treatment. The largest cohort study to date is the EPI3 study in France which compared the effectiveness and cost effectiveness of treatments for musculoskeletal disorders, upper respiratory tract infections, sleep disorders and anxiety and depression in more than 6000 patients. The study showed large effects. The homeopathically-treated group of patients tended to have more chronic illness patterns. The results showed that the patients treated with homeopathy needed only half as many prescriptions for non-steroidal anti-inflammatory drugs. For upper respiratory tract infections, the patients using homeopathy needed far fewer antibiotics. The cost saving to homeopathic GPs was a 20% reduction in spending. This study did not even consider the undoubted benefits of avoiding side effects of dangerous NSAIDs or the over-use of antibiotics.
• Grimaldi-Bensouda L, Begaud B, Rossignol M, Avouac B, Lert F, et al. (2014) 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 9(3): e89990
• Rossignol M, Begaud B, Engel P, et al. Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort. Pharmacopepidemiol. Drug Saf. 2012, 21:1093-101
• Colas A, Danno K, Tabar C, Ehreth J, Duru G. Economic Impact of Homeopathic Practice in General Medicine In France. Health Economics Review (2015) 5:18

In contrast to the UK, Switzerland carried out a review into the efficacy, safety and cost-effectiveness of homeopathy in 2011 and concluded that homeopathy was safe, effective and cost effective, and so it is now an integral part of the Swiss healthcare system.

So why do I read that homeopathy doesn’t work?
(Beats me)

Homeopathy may sound bizarre when looked at through the lens of the conventional medical paradigm. It is based on three fundamental principles:

• Like cures like – that a substance which causes a particular pattern of illness when taken by a healthy person, will cure that exact pattern of illness if found in a sick person.
• Use of the minimum dose – that a signal may need to be given only once for it to have an effect
• Dilution and succussion –homeopathically prepared medicines are diluted to negligibility, reducing their toxicity, but increasing their potency.

I hope you can see from this talk that there is significant and compelling evidence in the conventional scientific arena that homeopathy does work. This is added to the 200 years of data collected by the homeopathic community treating many millions of people.

Unfortunately, for some groups of people, this information seems to be intolerable. There is a very powerful attack on homeopathy in the media and in politics. Two very widely publicised reports in recent years, the House of Commons Science and Technology Committee Evidence Check 2010, and the Australian NHMRC review of Homeopathy have been used to say there is no evidence for the effectiveness of homeopathy. Let’s take these one at a time.

The House of Commons Science and Technology report:
Evidence for this was gathered by a committee of 14 MPs. They ignored the evidence given by medical homeopaths and instead gave weight to the soundbites of a journalist who gave no references. It was so badly constructed that only 3 out of the 14 MPs signed it. It prompted an Early Day Motion in parliament which was signed by 70 MPs and the report was rejected outright by parliament. In a scathing critique of the report written by Earl Baldwin of Bewdley ( he concluded:
“These limitations make the Committee’s report an unreliable source of evidence about homeopathy.”

The Australian NHMRC report 2015:
This has been extensively raked through and is now the subject of a complaint to the Commonwealth Ombudsman concerning the fraudulent way it was conducted, at the expense of the taxpayer. The problems with this report are very extensive, but in summary:
• Conflicts of interest – the NHMRC were planning to put out a statement to the effect that homeopathy was nonsense before they were forced to carry out a review. There was at least one member of the working committee who was a member of a prominent anti-homeopathy organisation.
• The CEO of the NHMRC, who in print had declared his bias against homeopathy, personally selected the 4 members of the Homeopathy Working Committee
• Against their own policy, the review did not include anyone who was professionally involved in homeopathy
• The first report was created by the person who had written the NHMRC guidelines on conducting good scientific reviews. He was sacked after he presented his findings to the NHMRC and his report was suppressed. Freedom of Information requests have shown that this review was assessed to have been of good quality. ***
• A second review of evidence was prepared. After it was completed, the NHMRC altered the findings and the protocol to extract the result they wanted. They brought in two arbitrary new rules of reliability of evidence which have never been used before or since in any review of any other medicine. These were that studies could not be included unless they had more than 149 participants, and that the Jadad score for quality had to be 5/5. As I say, this has never been asked of any other medicine. That these criteria were applied after the review was completed was hidden from the final publication and is a blatant breech of all protocols for conducting good scientific studies.
• After these criteria were applied, only 5 studies remained in the review, so their claim that they extensively reviewed 1800 studies was therefore false.
• Expert review of the NHMRC findings by the Australasia Cochrane Centre stated: “If the intent is to provide general statements about the effectiveness of homeopathy, then ‘no reliable evidence’ may not adequately reflect the research. For example, when a substantial proportion of small (but good quality) studies show significant differences, […] ‘no reliable evidence’ does not seem an accurate reflection of the body of evidence.” Again, this was ignored and hidden.

So there you have it. There are some very loud voices out there saying homeopathy doesn’t work, but their evidence is flawed or fraudulently manipulated. There is very good evidence for the effectiveness, cost-effectiveness and safety of homeopathy, in clinical use in people and animals, in plant and animal models and in in-vitro models. Basic science has shown that homeopathically-prepared ultramolecular solutions continue to retain traces of the substances from which they were formed.

Homeopathy works. Patients like it. It is cheap, safe, cost-effective and does not interact with other medications. It helps many people who have not been helped by conventional medicine.

*** August 2019 – NMHRC finally released the First Report – the author concluded that there is “encouraging evidence for the effectiveness of homeopathy” in five medical conditions.
NHMRC CEO Prof Anne Kelso clarified that NHMRC’s second Homeopathy Review published in 2015 “did not conclude that homeopathy was ineffective”, despite claims to that effect in media reports and by anti-homeopathy campaigners.
Interestingly, there has been no media coverage at all of this.