Homeopathy in the Era of Evidence Based Medicine

By Mirkamal Tolend

Homeopathy is guided by the principle that small doses of a substance that elicits a symptom in healthy patients can be effective in treating diseases that produce that same symptom.[1] This “like-cures-like” principle is akin to using caffeine to treat insomnia. The main rationale is to stimulate the body’s own healing capabilities with homeopathic preparations of these otherwise pathological stimuli.

Without knowing further about homeopathy, students of mainstream science may see that the guiding principle of homeopathy resembles vaccinations, or more precisely variolation, an obsolete practice in which patients were inoculated with small amount of smallpox virus that caused a mild but immunoprotective infection. This is the closest the two fields may come to converging, but ironically, homeopaths are often against vaccinations, and the analogy itself is invalid. Firstly, variolation and vaccines in general can only play a preventative role, whereas homeopathic remedies claim to work in both preventative and curative treatments. The mechanism of action is also different: vaccines work by mounting a lasting and measurable immune response in the host, which is not detectable when homeopathic remedies are administered.

Another difference that is much harder to reconcile–and often considered the last word in discrediting homeopathy–is that homeopaths maintain that their drugs increase in potency with further dilutions.1 Homeopathic drugs are often prepared using dilution factors ranging from orders of 103 to 10400 of their initial stock concentrations. While it is true that non-monotonic dose-response curves have been observed for some endocrine disruptor molecules,[2] the effects have never been as significant or generalizable as claimed in homeopathy. Not only does this idea directly contradict basic biochemical principles, but ultradilutions run into a very real physical problem often dubbed as the “Avogadro’s Limit.” Avogadro’s constant, 6.023×1023, is defined as the total number of constituent particles, such as atoms or molecules, in one mole of that substance. The value of this physical constant is corroborated by several independent methods, and is widely accepted. Serially diluting 1mol/L of anything down to 10-24 will give a 60% chance of finding a single homeopathic particle in the diluted 1L solution. Since most homeopathic pills are prepared using no more than a drop of diluted solution, and many compounds are diluted down to 10-400, it is hard to deny that homeopathic remedies do not contain any molecule of the active ingredient.

Homeopaths are well aware of this limitation, and argue that during the homeopathic dilution process, which involves vigorous shaking and slamming against an elastic plate at each serial dilution step (termed “succussion”), some spirit-like property of the substance becomes imprinted in the solvent molecules. Even after the last molecule of the substance is gone, the imprinted memory is thought to cause a physiological change. This is highly implausible, given that it contradicts many of the basic physical and biochemical principles that are at the foundation of effective modern-day treatments. Elaborate suggestions have been proposed over the years to support this imprinted memory effect. One group claims that ultradilutions still contain the original substance due to surface effects,[3] while others explain the imprinted memory effect by the epitaxy process (the transfer of structural orientation information from the solute to solvent), which leads to the presence of colloidal nanobubbles that contain active ingredients.[4] One study has even detected the presence of nanoparticles of the starting ingredients using advanced imaging techniques.[5] Even if these observations are valid, (for critiques, see[6],[7]) their biological significance would still need to be established.

It is not constructive to reject the possibility that technological limitations prevent us from detecting the homeopathic mechanisms of action. But it is also not ethical to hold onto a theory if it neither conforms to the current body of knowledge nor reliably predicts nature in experiments or observational studies. Randomized controlled trials and meta-analyses examining homeopathy’s effectiveness do not reliably illustrate an improvement over placebo,[8], [9] and even positive results are often weak and infrequent.[10], [11] Studies confirming the effects of homeopathy are conducted with serious design flaws, including biased outcome measurements, absent or ineffective controls and blinding, ineffective randomization, and insufficient sample sizes. The burden of proof still rests on the homeopaths. With the current evidence base, it cannot be established that homeopathy is better than placebo for any indication.

Despite the lack of evidence, homeopathy is still practiced in Ontario. As of November 2014, there are 258 homeopaths registered with the Ontario Homeopathic Association. Currently, homeopathic practice in Ontario is regulated at the provincial level by the Regulated Health Professions Act 1991 and the Homeopathy Act 2007. A transitional council is in place to provision the establishment of the College of Homeopathy of Ontario, which will oversee duties such as homeopath competency assessment, licensing, and quality assurance within the profession to enforce accountability and protection to the public. Homeopathic health products require a DIN-HM number to be sold in Canada, which may be obtained following a formal product licensing application to the Natural and Non-prescription Health Products Directorate (NNHPD) for evaluation of the products’ safety and effectiveness. To assess the effectiveness of the homeopathic product, the NNHPD accepts various types of evidence ranging from high quality systematic reviews of randomized controlled trials, all the way down to opinion reports, and references to traditional use. The government’s respect for freedom of choice and cultural diversity has kept assessment standards low–which, along with the scarcity of positive evidence in peer-reviewed medical literature–suggests that the majority of registered homeopathic products were approved based on low quality evidence. Nevertheless, all natural health products are prohibited from claiming to treat any condition listed under Schedule A of the Food and Drugs Act, which include acute or serious conditions such as congestive heart failure and cancer. Any homeopathic drug diluted outside the 10-24 to 10-60 range is also prohibited from carrying specific recommended indications, unless the safety profile (for both toxicity and potency) is established.

Why homeopathy persists alongside evidence-based medicine is a loaded question. The harsh reality is that not all patients’ chronic symptoms can be managed by mainstream medicine, and some will inevitably seek alternative medicine, perhaps justifiably so. Moreover, the general patient population may be gullible enough to accept the rationale of homeopathy and believe in its claims. Selective and uncritical media coverage of positive study findings, including buzz words like “nanoparticles,” will also help maintain public interest for at least a few more decades. Attractiveness of natural sources for the remedies and our acceptance of cultural diversity will likely protect homeopathy from widespread shunning.

Since homeopathy is here to stay, perhaps it is more constructive for mainstream medicine to make amends with it. With an open mind, we may even justify a benefit for having homeopathy as a placebo-based alternative. We may be too attached to the notion that treatment should demonstrate effectiveness over placebo. Instead, we should consider that homeopathy may act as an elaborate, spiritualistic form of placebo. It is easy to forget that patients do not have access to placebo treatments outside the research setting. Physicians, in effort to maintain their patient’s trust and to avoid ethical and legal ramifications, may be reluctant about prescribing placebos themselves. Recent meta-analyses show that the placebo effect is a significant part of the mainstream medical treatments’ effectiveness, especially for psychologically experienced conditions such as pain[12] and depression.[13] Placebo can not only be effective, but may even be better than the alternative drugs for certain patients. For instance, patients undergoing chemotherapy may experience pain or fatigue that cannot be managed adequately with standard drugs. Prescribing a placebo–or by extension, recommending homeopathy–may be an alternative to more potent drugs, because it would not be expected to cause adverse events or interact with chemotherapy.[14] There is definitely a lack of evidence to recommend homeopathy over placebo in reducing these persistent symptoms, but if it is found to be non-inferior to placebo, or more effective compared to no treatment, then perhaps homeopathy shouldn’t be discouraged.

Since homeopathy is a separate entity from mainstream medicine, it may escape some of the ethical limitations of prescribing placebo through the traditional system, and hence be a more viable alternative. The four classic principles of medical ethics need to be considered when assessing homeopathy’s utility as a placebo. The first principle, respect for autonomy, is most problematic for homeopathy and prescribing placebos in general. Respect for autonomy implies that homeopaths must not make unsupported claims about their remedies in order to allow for informed patient consent. Prescribing placebo through the traditional system involves complete deception, but the homeopathic deception is a relatively grey area. Uncertainties in the medical literature, and the lowered standards that govern the evidence base for homeopathic remedies may justify the suggestive claims by the homeopaths, and still allow for consent that is as informed as possible. Moreover, the unsuspecting general public might give homeopathy the benefit of the doubt, depending on their satisfaction with mainstream medicine. Compliance with the second principle of medical ethics, beneficence, may have been high at homeopathy’s inception in the 18th and 19th centuries, when sham remedies were certainly better than bloodletting and purging. Nowadays, the benefits are limited to the unpredictable effects of placebo, which may still benefit some patients. Non-maleficence, the third principle, uncovers important issues. Adverse events form homeopathy are unlikely,12 especially compared to other forms of alternative medicine. However, if seeking homeopathic care either delays or interferes with the delivery of available and effective mainstream care, then the homeopath would have done harm. The Ontario Health Insurance Policy does not cover homeopathic or other alternative medicine expenses, which might serve as a financial deterrent to mitigate this problem. A 2005 Ontario survey identified several weakly significant independent predictors for seeking homeopathic care, including being female (odds ratio 1.27), residing in a rural area (1.30), and having a college or university degree (2.02 and 1.69, compared to less than high school).[15] Odds ratios for household income and age were not significant. More research is needed to assess whether homeopathy is affecting mainstream medicine and whether high-risk patients groups are being exploited. Fourth and finally, the justice principle, which advocates equal access to healthcare resources, is probably more applicable in other regions of the world such as Europe, where homeopathic care is partly funded by governments. Formation of the regulatory body for homeopathy in Ontario within the next few years may further help protect the public interest.

Alternative forms of medicine will always persist for reasons beyond scientific rationality. Perhaps no number of negative clinical trials will change this. At present, homeopathy is what appears to be the best of the alternatives, simply for its low risk and potential of being a practical placebo. Until more plausible mechanisms of action are corroborated in basic science studies of homeopathy, our limited research resources should focus on studying motivations for its use, rather than trying to establish its effectiveness against placebo in clinical trials. At the public health level, the current safeguards are important, and need to be continually enforced and refined. Public awareness of regulations already in place should be promoted so that patients stay vigilant while using homeopathy. Both policy-makers and the public will benefit from research efforts aimed at studying the pattern of use of homeopathy, and finding better strategies to refine its utility as placebo. Qualitative methodologies to examine the sources of dissatisfaction within the mainstream medicine may be helpful in identifying areas for improvement, which may also help shape the use of alternative medicines to maintain a safe and effective delivery of care.

References

[1]. Hahneman S, Organon of Medicine. Germany: W.F. Wakeman: Germany; 1833. Available from: http://www.homeopathyhome.com/reference/organon/organon.html

[2]. Andrade AJ, Grande SW, Talsness CE, et al. A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on rat brain aromatase activity. Toxicology. 2006;227(3):185-92.

[3]. Chatterjee BK. The mathematics of dilution. Homeopathy. 2014 Apr;103(2):143-6.

[4]. Rao ML, Roy R, Bell IR, et al. The defining role of structure (including epitaxy) in the plausibility of homeopathy. Homeopathy. 2007 Jul;96(3):175-82.

Erratum in: Homeopathy. 2007;96(4):292.

[5]. Chikramane PS, Suresh AK, Bellare JR, et al. Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Homeopathy. 2010;99(4):231-42.

[6]. Kerr M, Magrath J, Wilson P, et al. Comment on “The defining role of structure (including epitaxy) in the plausibility of homeopathy”. Homeopathy. 2008 Jan;97(1):44-5; author reply 45-6.

[7]. Journal Club – “The defining role of structure (including epitaxy) in the plausibility of homeopathy”. [Forum on the Internet]. Bad Science; 2015 [updated 2010 Dec 22; cited 2014 Dec 18]. Available from: http://www.badscience.net/2000/01/journal-club-the-defining-role-of-structure-including-epitaxy-in-the-plausibility-of-homeopathy/

[8]. Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet. 1997;350(9081):834-43. Erratum in:Lancet 1998 Jan 17;351(9097):220.

[9]. Shang A, Huwiler-Müntener K, Nartey L, et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet. 2005;366(9487):726-32.

[10]. Kassab S, Cummings M, Berkovitz S, et al. Homeopathic medicines for adverse effects of cancer treatments. Cochrane Database Syst Rev. 2009;(2):CD004845.

[11]. Mathie RT, Lloyd SM, Legg LA, et al. Randomized placebo-controlled trials of individualized homeopathic treatment: systematic review and meta-analysis. Syst Rev. 2014;3(1):142.

[12]. Puhl AA, Reinhart CJ, Rok ER, et al. An examination of the observed placebo effect associated with the treatment of low back pain – a systematic review. Pain Res Manag. 2011;16(1):45-52.

[13]. Rief W, Nestoriuc Y, Weiss S, et al. Meta-analysis of the placebo response in antidepressant trials. J Affect Disord. 2009;118(1-3):1-8.

[14]. Dantas F, Rampes H. Do homeopathic medicines provoke adverse effects? A systematic review. Br Homeopath J. 2000;89 Suppl 1:S35-8.

[15]. Williams AM, Kitchen P, Eby J. Alternative health care consultations in Ontario, Canada: A geographic and socio-demographic analysis. BMC Complement Altern Med. 2011;11:47.