Homeopathic “medicine” suffers second-class status in relation to its scientific counterpart, allopathic medicine. This is largely because homeopaths have chosen to immerse themselves in irrational ideas about the healing power of infinitesimal dilutions. Continuing education courses still teach participants how to prescribe homeopathic remedies despite the lack of validation and a solid factual foundation. Homeopaths have failed to provide solid proof of effectiveness even after two centuries of practice. In light of this, more medical practitioners are coming to realize that classical homeopathy may actually equate to a highly ritualized means of recommending costly placebos. In Great Britain, for example, government agencies that formerly backed homeopathy are contemplating elimination of National Health Service coverage for homeopathic care precisely on account of this concern. Given the pressure on homeopaths to produce clear evidence of benefit, one might think that a recently published clinical trial might silence the skeptics. This study, by University of Helsinki veterinary medical faculty, showed that a “homeopathic” combination called “Zeel” successfully treated chronic pain in osteoarthritic dogs.1 The study was randomized, double-controlled and double-blinded. The investigators received multiple sources of funding in addition to that from the makers of Zeel (Heel of Germany), thereby reducing suspicion of sponsor bias. The collected data reflected outcomes of several indices including mobility, force plate impulse generation and chronic pain. Zeel outperformed placebo and achieved statistical significance though it failed to deliver the improvement afforded by carprofen, the positive control. Unfortunately, the authors omitted sufficient details about the force plate data that would have allowed further scrutiny; this study nevertheless lends insights into the value of Zeel for chronically painful dogs. The problem is that Zeel is not truly homeopathic in the classic sense. Homotoxicology vs. Homeopathy To clarify, Zeel and related compounds made by the manufacturer Heel of Germany fall under the heading of “homotoxicology.” This 20th century modification to homeopathy brings the discipline much closer to accepted principles of medicine, pathology and pharmacology. While Zeel’s ingredients have been diluted, their concentrations rank nowhere near the infinitesimal end of the spectrum where homeopathic agents commonly reside. Homeopathic prescribing principles assert that higher dilutions have higher potency. In contrast, Heel Germany reportedly chose to improve the strength of Zeel by concentrating the product, not by further diluting it.2 Thus, unlike homeopathic remedies that are watered down to levels where pharmacologic activity may be neither likely nor possible, homotoxicologic remedies contain substances in sufficient amounts to alter biological activity.3,4 Evidence documenting the anti-inflammatory effects of Traumeel, a sister compound to Zeel, suggests that Traumeel works by inhibiting the secretion of pro-inflammatory cytokines and by modulating the activity of macrophages with the end result of ramping down inflammation.5,6 Homotoxicologic compounds thus demonstrate measurable mechanisms of action and outcomes. Assorted other differences distinguish homeopathy from homotoxicology. Homeopathic dilutions of plants, minerals or animal parts purportedly counteract the symptoms caused by larger doses of the same substance according to the “like cures like” principle. In homotoxicology, however, mother tinctures (i.e., the undiluted extracts from which dilutions are made) show activity similar to the diluted versions. Homotoxicologic agents consist of mixtures rather than one pure substance. Zeel, for example, contains a smorgasbord of plants (including comfrey, a source of pyrrolidizine alkaloids), minerals (e.g., sulfur), and pig parts (i.e., embryo, placenta, umbilical cord and cartilage). Considering the promise of stem cells for joint deterioration, these porcine components may yield stem cells as their contribution to offsetting the pain of arthritis. Finally, whereas classical homeopaths may administer a one-time dose of a single remedy for a patient based on an excruciatingly detailed history, homotoxicologic preparations are given daily to a range of patients without regard to personality quirks but instead grouped according to medical conditions. Ultra Low Doses (ULD) The rapidly expanding scientific literature exploring ULD prescribing shows that minuscule doses of some substances not only affect physiology but they can also lead to surprises, both positive and negative.7 That is, the alter ego of the drug administered at ULD can vary dramatically from higher doses of the same drug.8 For example, a daily ULD of the alkylating agent melphalan reduced the severity of experimental colitis in mice. At the much higher antineoplastic dose, melphalan becomes a potent inducer of cellular stress responses whereas at ULD, it guards against cytotoxicity by blocking TNF-a, helping to protect the body against inflammation.9 ULD naloxone attenuates the release of pro-inflammatory cytokines, adjusts signal transduction and reduces neuroinflammation in the spinal cord, leading to a less painful physiologic state.10,11 In larger doses, naloxone counteracts the effects of opioids and would increase nociceptive transmission. ULD aspirin produces prothrombotic effects, exposing a detrimental downside to this otherwise broadly accepted cardiac risk deterrent and blood thinner at higher doses.12,13 Enlightened by the evidence on ULD and homotoxicology, integrative medical practitioners need not resign themselves accepting irrational belief systems from past centuries and the New Age. Like Lewis Carroll’s Alice in Wonderland, who faced both sensical and nonsensical elements as she engaged in a world of miniatures, those who pursue nanopharmacologic prescribing need to remember to keep their head about them. Shifts in cytokines and intercellular signaling along with subtleties in receptor regulation require more concerted effort to grasp than claiming to influence some mystical vital force. Perhaps ultra-low dosing was what Samuel Hahnemann, homeopathy’s founder, was targeting all along, well before the system of low-dose prescribing got sidetracked into absurdity of logic and proportion. <HOME> Narda Robinson, DVM, DO, Dipl. ABMA, FAAMA, offers an evidential and scientific perspective on the latest trends in complementary and alternative veterinary medicine. She oversees complementary veterinary education at Colorado State University. This article first appeared in the May 2010 issue of Veterinary Practice News FOOTNOTES 1. Hielm-Björkman, Tulamo R-M, Salonen H, et al. Evaluating complementary therapies for canine osteoarthritis – Part II: a homeopathic combination preparation (Zeel®). eCAM. 2009;6(4):465-471. 2. Hielm-Björkman, Tulamo R-M, Salonen H, et al. Evaluating complementary therapies for canine osteoarthritis – Part II: a homeopathic combination preparation (Zeel®). eCAM. 2009;6(4):465-471. 3. Ernst E and Schmidt K. Homotoxicology – a review of randomized clinical trials. Eur J Clin Pharmacol. 2004;60:299-306. 4. Valentiner U, Weiser M, Moll I, et al. The effect of homeopathic plant extract solutions on the cell proliferation of human cutaneous fibroblasts in vitro. Forsch Complementärmed Klass Naturheilkd.2003;10:122-127. 5. Schneider C, Schneider B, Hanisch J, et al. The role of a homoeopathic preparation compared with conventional therapy in the treatment of injuries: an observational cohort study. Complementary Therapies in Medicine. 2008;16:22-27. 6. Porozov S, Cahalon L, Weiser M, et al. Inhibition of IL-1β and TNF-α secretion from resting and activated human immunocytes by the homeopathic medication Traumeel ® S. Clinical & Developmental Immunology. 2004;11(2):143-149. 7. Senn R, Keren O, Hefetz A, et al. Long-term cognitive deficits induced by a single, extremely low dose of tetrahydrocannabinol (THC): behavioral, pharmacological and biochemical studies in mice. Pharmacology, Biochemistry and Behavior. 2008;88:230-237. 8. Shurin GV, Tourkova IL, Kaneno R, et al. Chemotherapeutic agents in noncytotoxic concentrations increase antigen presentation by dendritic cells via an IL-12-dependent mechanism. The Journal of Immunology. 2009;183:137-144. 9. Shmarina G, Pukhalsky A, Alioshkin V, et al. Melphalan reduces the severity of experimental colitis in mice by blocking tumor necrosis factor-α signaling pathway. Ann NY Acad Sci. 2007;1096:97-105. 10. Lin S-L, Tsai R-Y, Tai Y-H, et al. Ultra-low dose naloxone upregulates interleukin-10 expression and suppresses neuroinflammation in morphine-tolerant rat spinal cords. Behavioural Brain Research. 2010;207:30-36. 11. Tsai R-Y, Tai Y-H, Tzeng J-I, et al. Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin-treated rats and prevents glutamate transporter downregulation by suppressing the p38 mitogen-activated protein kinase signaling pathway. Neuroscience. 2009;159:1244-1256. 12. Aguejouf O, Eizayaga F, Desplat V, et al. Prothrombotic and hemorrhagic effects of aspirin. Clinical and Applied Thrombosis/Hemostasis. 2009;15(5):523-538. 13. Doutremepuich C, Aguejouf O, Desplat V, et al. Aspirin therapy: an attempt to explain the events of prothrombotic complications after treatment discontinuation. Thrombosis and Haemostasis. 2010;103:171-180. Homeopathic “medicine” suffers second-class status in relation to its scientific counterpart, allopathic medicine. Homeopathic “medicine” suffers second-class status in relation to its scientific counterpart, allopathic medicine. Homotoxicology, Homeopathic medicine, Homeopathy, homeopaths, Homotoxicologic, ULD