FIFTH QUEENSLAND POULTRY SCIENCE SYMPOSIUM
Gatton College, July 1996
CONCERNING EMU OIL AND ITS POTENTIAL ANTI-ARTHRITIC ACTIVITY
Michael W Whitehouse
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Q 4102 . .. .
Peter B Ghosh
Department of Surgery, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065.
Athol G Turner
Department of Chemistry, Sydney Institute of Technology, Ultimo, NSW 2007
This report provides some background material and then briefly summarises the evidence that Emu Oil contains active principles that may be valuable for treating chronic inflammation, based on experimental studies in rats with established polyarthritis.
Traditional beliefs of geographically widely separated Aboriginal communities agree on the beneficial properties of Emu Oil as a natural remedy to reduce pain and stiffness in sore muscles and joints. Documented records of this practise date back well over 100 years, as cited in the US Patent (1) e.g. Leichardt 1847; Bennett 1860; Old bushman 1891. Apparently the oil must be massaged vigorously on to the sore muscle or joint and the process repeated as often as required: hence pressure, heat and duration of rubbing are all relevant factors (2). For many affected tissues, applying the raw oil in this form must itself be quite a painful process.
Several commentators have asserted that the pharmacological value of the oil is unproven, i.e. lacking scientific investigation, on the ground but such information has not been found in their literature searches. Sceptics might assert that the transdermal (?painful) application of the oil seems to resemble the use of certain well-known counter-irritants such as capsaicin, the pugent principle of red peppers (3), which transiently produce local pain and/or inflammation but subsequently induce a long-lasting state of pain relief (analgesia). Alternatively, applying the oil might be considered merely a means of inducing a ‘placebo effect’ i.e. a non-specific ‘comforting’ response, since there is data suggesting that some 40-60% of patients with soft tissue and local joint disorders will respond to a placebo when rubbed into the skin (4).
In recent years, topical formulations of some well-established non-steroid anti-inflammatory drugs (NSAID) have been developed by the drug industry mainly to treat arthritis, muscle sprains and soft tissue trauma (5,6). The use of this term “Topical” may mean to treat the local inflammation by a simple local applicati0on. It may also imply transdermal delivery of a drug through the skin for it to have a systemic effect on some distant tissues, other than the skin. For emu oil to seriously compete for attention in the market place against these now heavily promoted, transdermally-active NSAIDs, it is essential to establish that there really are constituents in emu oil which can match these NSAIDs in efficacy after dermal application.
These transdermal NSAIDs are now gaining acceptance because they fulfil expectations of being able to ‘perform’, in as much as the active NSAID is provided (I) in a known amount, (ii) in a form known to fairly rapidly penetrate the skin and (iii) with anticipated efficacy based on prior knowledge that it will control both experimental and clinical inflammation when delivered by other routes.
Emu oil (concentrates) need to match these topical NSAIDs in all these respects if they are to gain maximum credibility and (a) reclaim ground already lost to the new topical NSAID formulations or (b) successfully capitalise on the general public’s growing acceptance that a transdermal agent may bring genuine relief from systemic inflammatory/pain-generating disorders.
It should be noted that topical NSAIDs are not entirely free from some of those side-effects (regularly seen after their oral use), and in this respect they are not necessarily a great advance on previous formulations of those same NSAIDs (see ref7 for renal toxicity).
The key to certifying the therapeutic value of the emu oil is to have, and use, a well-controlled small animal model of inflammatory disease that responds beneficially to known anti-inflammatory drugs. Since any topically-administered agent may be slow to penetrate through the skin, it is essential either to apply the test medication well in advance of an experimentally induced inflammation that has a rapid onset; or alternatively to use an experimental model of inflammation that is slow-developing.
Extensive work at the Australian National University (8), the University of Adelaide (9) and more recently at the University of Queensland had indicated that the experimentally-induced polyarthritis in rats, obtained by inoculating a mycobaterial adjuvant (10) is well-suited to evaluating the transdermal efficacy of both synthetic drugs and certain natural products as significant anti-inflammatory agents. In essence rats (from a susceptible strain) are given the adjuvant by tail-base injection on day 0 and the disease is allowed to develop until the first signs of arthritic inflammation are clearly expressed, 10 to 12 days later. At this time the size of rear paws and maximum tail thickness are measured with a micrometer, the severity of inflammation in the front paws is given a score on a arbitrary scale (0-4+) and the body weight is measured after shaving an area of skin on the upper back of the rat, approx. 6cm, just below the neck. The test formulations are applied once daily for four days and on the fifth day the signs of inflammation are re-evaluated. Suppression of both the paw swelling and of the disease-associated weight loss indicates successful treatment. Animals are observed for a further three to four days, after suspending treatment: nearly always there is a rebound in the signs of arthritis in the successfully treated group. This indicates that the drug is truly anti-inflammatory and that these treated animals re not “false-positives” (in the sense of failing to respond to the original arthritigen).
Feeble drugs such as methyl salicylate or aspirin derivates show little activity when applied transdermally in doses < 150 mg/kg/day. Many NSAIDs are active at doses 1-20 mg/kg/day, but may still cause some gastric bleeding even though given non-orally in these experiments. Unpublished studies carried out at the University of Adelaide 1988-1992 established the efficacy of emu oil as an anti-inflammatory agent in delaying/preventing arthritis development without compromising the stomach (in contrast to most NSAIDs). Some of these finding were published in a US patent (1) to justify claims made therein. Further studies, as yet unpublished, identified very potent fractions (active at less than 5 mg/kg). These are now being analysed to identify chemical “markers” of activity that might be used to certify and standardise different batches of oil, for likely anti-inflammatory potency.
While this particular animal model of experimental arthritis has delivered useful date, it certainly needs to be supplemented with other whole animal pharmacological assays to characterise other possible medicinal benefits of the oil. The wound-healing models using rats, currently being studied in Perth and Brisbane, should allow insight into any effect the oil may have on hastening repair of traumatised tissue and healing after bruising.
Earlier studies in Adelaide indicated the oil was not very active in reducing fever or suppressing rapidly-developing, but transient, models of acute inflammation (e.g. oedema induced in rat paws by inoculating irritants such as histamine or carrageenan). These rather negative findings at least indicated that emu oil lacked aspirin-like activity. [This was in fact a helpful finding, since we already have an abundance of aspirin-like drugs in the market place.] Rather, it positioned emu oil as a potential medication with activity ‘beyond aspirin’ i.e. that might control chronic inflammation (rather than acute transitory oedema etc.) and therefore of possible value for treating sustained inflammatory disorders like rheumatoid arthritis, as well as post-surgical trauma.
‘Activity’ refers to anti-inflammatory/arthritis-suppressant action as seen in this rap polyarthritis model after dermal application i.e. by rubbing on and into the skin.
1. The oil is not particularly effective, applied dermally, without an additive to enhance skin permeation. It is this combination of oil and enhancer, which is the essential core technology of these patents. Enhancers include esters of salicylic acids, which are not very efficient in preventing signs of rat arthritis by themselves, but certainly provide analgesic and antipyretic benefit.
2. The normal fatty acid components of the oil (and most other animal fats) are almost certainly not the active principles. Plant oils with a similar content of oleic acid (canola, olive) were not active. These and other observations rule out the ‘placebo effect’ as an explanation for the observed ‘activity’ of dermally applied emu oil.
3. The activity in the crude oils may be destroyed by light, due to the presence of a photosensitising yellow pigment.
4. The ‘activity’ may also be impaired/destroyed by some of the rather harsh processes being used to prepare a highly acceptable cosmetic product.
5. The ‘activity’ can be concentrated more than 100-fold from certain batches of oil to give a stable fraction with remarkable potency, inasmuch as it can be given along with the arthritigen and effectively switch off disease development; in this respect resembling some of the powerful immunosuppressant drugs that are now being studied as alternative treatments for rheumatoid arthritis, e.g. cyclosporin-A.
6. Activity ahs been ascertained in oils from emus raised Western Australia, Tasmania and Queensland but not similar oil fractions prepared from free-range chickens and other domestic animals (pigs, goats).
7. The inactive fraction (>90% volume) of these particular emu oils was a useful vehicle for transdermal delivery of other lipid-soluble drugs e.g. cyclosporin.
8. Further work, beyond that described in the patent (1), has shown the ‘activity’ can be separated from the yellow (photosensitising) components to provide a more durable, seemingly light-resistant, commodity.
9. No sample of emu oil tested to date has shown any of the gastro-irritant effect associated with conventional NSAIDs (even when these latter drugs are given transdermally).
10. Finally it must be emphasised that not all samples of emu oil tested against this rat arthritis have shown activity: clearly there are oils and oils, i.e. + or 0. Furthermore, even A grade oil may be inactive if given orally i.e. by mouth, instead of transdermally by rubbing on.
The impetus to carry out these studies arose originally in Western Australia, largely due to the enthusiasm and support of P Clark, J Leach, D Williams and their Aboriginal partners in the Emu industry. Unfortunately the early momentum could not be sustained. So we now find ourselves in the position of trying to catch up with some quite high-powered development work being undertaken in Canada, the USA, China and France to further establish the potential medical benefits of emu oils. Fortunately there are concerned scientists in the Department of Agriculture WA (J Snowdon, P Frapple) and Qld Department of Primary Industry (C Davis, P Kent) who are looking for ways to help retrieve this situation.
Concerning the future, it is imperative that we all try and find some answers to at least two difficult questions:
1. How do the conditions of bird husbandry, particularly those relating to feed and environment, affect the yield and stability of effective oil. Present practices for optimising meat yields and leather quality may not necessarily be the most appropriate for enhancing production and storage of the therapeutic factor (s) in emu fat.
2. How seriously is the industry prepared to promote further essential research and development? This is absolutely necessary to establish future certification by the Therapeutic Goods Administration (TGA) in Canberra and related regulatory bodies overseas e.g. the Food and Drug Administration (FDA) in the United States, to allow claims regarding therapeutic benefit (s) of emu oil products when sold openly through pharmacies, supermarkets, etc. It is no use just waiting for a government agency to step in with the requ9isite funding: it will be slow coming and unlikely to be sufficient. The industry needs to take the initiative here to ensure it is not a case of ‘too little too late’.
Unless we can wrestle with these problems now, we may as well give away the idea of realising a high financial return on a low volume product – namely stabilised and standardised emu oil concentrates with proven clinical efficacy for treating musculo-skeletal pain and inflammation.