Written By Tan Kok Hsien, Class of 2013
Introduction
Traditional Chinese Medicine (TCM) is one of the earliest form of medicine which is still widely practiced in today’s world. Its practice mainly involves the use of herbs (and including animal parts and minerals), acupuncture, moxibustion, cupping etc. for the prevention and treatment of illnesses, based on its unique set of theories including Yin Yang, Five Elements, Zang-fu etc.
In today’s world, there is an impetus to validate TCM practices and/or theories, and harness the best of this system that has proven its value by the test of time, yet remains unsatisfactorily proven and explained by modern scientific standards. Research in TCM is gaining traction in the world and there are several types of TCM research ongoing. This article aims to briefly introduce the different types of TCM research and preliminarily discusses their challenges and its significance in progressing TCM, modern medicine and healthcare.
Clinical studies
Contrary to pharmaceutical studies where scientists start with drug design and discovery, proceed to animal testing and finally to clinical trials in humans, TCM research often start with clinical trials, and if a certain treatment is proven effective, it will proceed to investigate the mechanism of action. This is generally so as TCM has already been used on humans for thousands of years and therefore proven to be relatively safe. Nevertheless, due to the nature and core philosophy of TCM that every individual is unique and therefore treatment is unique to every individual, there is no basis for modern scientific comparison, and efficacy can only be considered anecdotal. Clinical trials today basically aim to prove the efficacy of a certain treatment for a particular disease condition, as much as possible, by modern scientific standards. Notwithstanding the core conflict in philosophy, current studies try, at best, to go around this by investigating only a particular syndrome-type of patients of a particular disease condition, so that variability in treatment can be kept to a minimum. Nevertheless, until the day where innovative and novel statistical methods and evaluation designs can accommodate such variability in TCM, it will be hard to truly prove the efficacy and wisdom of TCM.
By today’s standards, a randomized controlled trial (RCT) is one of the most powerful tool in research. In a RCT, participants are allocated at random to one of several groups, where one of the groups would be a control group that either do not receive any treatment, receive a placebo, or undergo current standard treatments; the test groups would undergo the treatment to be proven. The comparison of the treatment outcome between these groups would suggest whether a particular treatment is effective or of clinical significance.
For example, in a recently concluded RCT in Singapore, a group of western doctors and TCM physicians studied whether acupuncture and herbal formulation is effective when compared to artificial tears alone, in the treatment of dry eye symptom. The control group was treated with artificial tears alone (standard treatment), while another 2 groups were treated additionally with acupuncture or oral herbal prescription respectively. They found that acupuncture is safe and provides additional benefit in mild to moderate dry eye, compared to artificial tears alone.[1] This provides evidence for the recommendation of acupuncture, on top of current standard treatment, for the management of dry eyes.
The above example is one of the successful projects under the Singapore Ministry of Health TCM Research Grant which was rolled out in 2014 to encourage collaborative research between western doctors and TCM physicians so as to build an evidence base for the use of TCM.
Acupuncture can be considered the most widely accepted TCM treatment modality by the international community. WHO has published in 2003 a list of over 100 diseases, symptoms or conditions that acupuncture can be indicated for, of which 28 has been proven through controlled trials to be an effective treatment. Many years has passed since 2003 and many more studies have been carried out since, with better study designs and bigger sample sizes, to support the use of acupuncture.
Clinical studies are aplenty and span different disease conditions and different TCM modalities. This is the first step for TCM to move beyond anecdotal evidence (considered weak evidence) to scientific and statistically proven evidence, and to justify the continued use of TCM in today’s modern medical landscape.
Phytochemical/Pharmacological studies
Herbal prescriptions and decoctions is one major treatment modality in TCM. While TCM physicians base their choice of herbs for a person’s condition on TCM theories, a modern scientist is interested in the chemical components of the herbs, specific compounds that are biochemically active in the human body, and the mechanisms by which these compounds work. Advanced studies would look at the interactions between different herbs (and their compounds) or their potential interactions with western drugs.
Chemical Components, Identification and Authentication of herbs
Studies on the chemical components, identification and authentication of TCM herbs started decades ago and have achieved significant progress. In the past, it is not uncommon for 2 herbs of different species to be used interchangeably because of their similar looking appearance. A classic example is the pair of Han Fangji 汉防己 (Stephania tetrandra) and Guang Fangji 广防己 (Aristolochia fangchi). Both plants are commonly known as Fangji in TCM. While the roots of Han Fangji have commonly been used as a safe diuretic, antirheumatic and analgesic agent in China for centuries[2], Guang Fangji contains aristolochic acid, a known carcinogenic and nephrotoxic compound. With development of techniques such as high performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS) and hyperspectral imaging (HSI), identification and quality control of Fangji[3-5] is not a problem anymore.
Such analytical techniques, among others, are also commonly employed to study the chemical components and establish industry standards for other herbs. This is important as even for herbs of the same species, different batches of harvest and in different growth environments could result in herbs of differing concentration of active chemical compounds. The Hong Kong Chinese Materia Medica Standards (HKCMMS) Office set up by the Hong Kong Department of Health has in recent years established standards for some commonly used TCM herbs, and to date, published 8 volumes of HKCMMS covering standards for a total of 275 herbs (http://www.dh.gov.hk/english/main/main_cm/main_cm.html).
Mechanism of Action and Drug Discovery
With the chemical components of individual herbs worked out, the next step would be to find out which are the biochemically active ones that could potentially be of therapeutic effect and how.
For example, the famous Ginseng is used in TCM to tonify Qi, promote vitality and prolong life. Studies have shown that Ginseng shows effects against a variety of conditions including diabetes, depression, fatigue, ageing, inflammation, tumours, dyspepsia, stress and ulcers[6]. The pharmacological effects of ginseng are derived from its multiple active ingredients including ginsenosides, ginsengosides, polysaccharides, peptides, phytosterols, polyactylenes, polyacetylenic alcohols, and fatty acids[7-12]. In one study, Cheng et al reported that ginsenoside Rg1 and Rb1 could increase neural plasticity in efficacy and structure, and that despite having common effects, there are some differences in pharmacology and mechanism[13]. Ginseng is one of the better studied herbs and yet there are many areas in its efficacy and mechanism of actions that remains to be clarified, needless to mention the hundreds of other commonly used herbs in TCM.
The dream of any scientists doing this work would be to develop a particular compound further and eventually discover a new (western) drug. Tu Youyou’s discovery of artemisinin (from TCM herb Qinghao) for the treatment of malaria which won her the 2015 Nobel Prize in Physiology or Medicine is a hallmark example.
Other than mechanistic actions of herbs, the mechanism of acupuncture is another popular research topic. While acupuncture has achieved certain level of evidence that it can alleviate certain conditions, the mechanism by which it works still baffle many. The British Acupuncture Council has a website (https://www.acupuncture.org.uk/category/a-to-z-of-conditions/a-to-z-of-conditions.html) that puts together research fact sheets on some 60 conditions which provide summaries of research on clinical trials as well as potential mechanisms of action.
Herb-herb and herb-drug interactions
When prescribed by a TCM physician, multiple herbs are often used in combination, known as a formula. Based on TCM principles, different herbs are mixed and matched, and ‘formulated’ deliberately according to six basic modes of herb-herb interaction namely reinforcement, potentiation, restraint, detoxification, counteraction and toxicity[14]. In classical formulas, the ratio of each herb to be used in the formula is even fixed and said to hold importance in its efficacy.
Interactions between herbs (their chemical components) could bring about desirable synergistic effects or undesirable antagonistic effects and this could take place and change at different ratio of herbs used, processing methods of herbs, and length of cooking time. Research in this area aims to determine whether there is any scientific basis for the purported synergistic (or antagonistic) effects of herb combinations.
Dang Gui Bu Xue Tang (DGBXT当归补血汤) is an ancient formula to exemplify such effects. DGBXT is a simple formula made up of only 2 herbs Radix Astragali 黄芪 (RA) and Radix Angelicae Sinensis 当归 (RAS), and specifically used in the weight ratio of 5:1. Chemical evaluation showed that main active constituents in DGBXT were most abundant after extraction at the RA to RAS ratio of 5:1, whereas other tested RA to RAS ratios only gave sub-optimal levels of the active constituents. Biological evaluation also indicated that bioactivities of DGBXT, e.g. immuno-modulatory, oesteotropic and estrogenic effects were also best exerted at this ratio[15].
Nevertheless, such research gets exponentially challenging when the concoction of herbs gets big and the potential interactions between the multitude of components of all the herbs put together becomes enormous.
Compared to herb-herb interactions, western doctors are more interested in herb-drug interactions. It is common in Singapore that many patients take TCM concurrently with western medication without informing their western doctor, as patients know western doctors tend to advise against it. Such reactions from western doctor are not unfathomable as they do not understand TCM, and are wary that TCM medication can interact and interfere with the efficacy of the medicine they prescribe. Indeed, some herbs have been shown to interact with specific drugs. The better-known ones are: Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine; Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone; St John’s wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline[16].
It is, however, important when evaluating such studies to note whether the methods employed in such studies are reflective of reality. For example, were the methods of extraction/administration or the amount used of the herb in the studies reflective of that in real practice? Or, if the herb-in-question when used in combination with other herbs could potentially negate the effect of the purported dangerous herb-drug interaction.
Regardless, it is important to acknowledge the dangers of herb-drug interactions, and TCM physicians should keep themselves relevant with latest findings in this research field to avoid any potential mishaps to their patients due to their concurrent intake of TCM and western medication.
Research on TCM theories
Examples of research done to validate TCM theories include proving the physical meaning of Yin Yang[17, 18], the TCM theory on the different ‘flavours’ (characteristics) of herbs[19], studying models to better define the concept of TCM ‘syndromes’[20] and existence of acupuncture meridians[21-23] etc. Attempts to prove TCM theories are not uncommon, but do not make a majority of TCM research. Clinical trials to prove efficacy, and research on mechanisms of action of effective treatments should be of higher priority to prove the value of TCM in the face of modern medicine.
Health Services Research (HSR)
Health services research is the multidisciplinary field of scientific investigation that studies how social factors, financing systems, organizational structures and processes, health technologies, and personal behaviours affect access to health care, the quality and cost of health care, and ultimately our health and well-being. Its research domains are individuals, families, organizations, institutions, communities, and populations[24]. In short, it goes beyond basic and applied research to look at how multiple factors could affect/improve healthcare. Chapter 8 of ‘Patient Safety and Quality: An Evidence-Based Handbook for Nurses’ gives a good introduction on HSR.
In the field of TCM, HSR could help to show the value of TCM in the healthcare landscape. For example, to study the impact of TCM usage on the quality of life of cancer survivors. In another instance, a comparison study between the western/TCM integrated system of medical practice (e.g. in China where a doctor is trained in both medical system) and the team-based care model of practice involving separate western and TCM physicians could shed light on the pros and cons of each model, and provide a direction for the future of integrative medicine.
HSR is a relatively new field of research, and there is much that TCM can prove, beyond basic and applied research (especially if current scientific techniques cannot accommodate the variability of TCM treatment), to show policymakers the importance and value of TCM.
TCM Research Landscape in Singapore
There is a lot of work that TCM physicians or its researchers can and need to do if they wish to gain a foothold in mainstream medicine. Unfortunately, most TCM physicians are not equipped with the knowledge and skills to conduct high level research as these are not part of the routine undergraduate TCM education. While western doctors can be equally clueless about research when they graduate with a MBBS, they have more structured avenues to pick up research skills, such as undertaking the NUS Masters in Clinical Investigation, or be under the tutelage of a mentor in structured hospitals or research institutes. Such opportunities are lacking in the TCM field. Due to the unique developmental background of TCM in Singapore where TCM has always been considered complementary, privately or VWO-run and non-subsidised, current senior physicians who were trained in the earlier days are mostly interested in clinical work and lack experience in research to lead younger physicians. Many run their own clinics (and make good money) and they do not see the value and returns for them to spend time on research. As NTU started the double degree in Biomedical Science and Chinese Medicine in 2005 to formally train high calibre students trained in TCM, and MOH started the TCM Research Grant in 2014, these are moves to encourage TCM research and opportunities to collaborate between western doctors and TCM physicians so that the TCM sector can gradually build up its research capabilities. This will take some years but we must not give up. I believe TCM remains as a treasure of knowledge for breakthroughs and betterment of the current healthcare and medical scene.
References
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2. Achike, F.I. and C.-Y. Kwan, Characterization of a novel tetrandrine-induced contraction in rat tail artery. Acta pharmacologica Sinica, 2002. 23(8): p. 698-704.
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20. Xiao-Bo, Y., et al. A classification algorithm for TCM syndromes based on P-SVM. in 2005 International Conference on Machine Learning and Cybernetics. 2005.
21. Schlebusch, K.-P., W. Maric-Oehler, and F.-A. Popp, Biophotonics in the Infrared Spectral Range Reveal Acupuncture Meridian Structure of the Body. The Journal of Alternative and Complementary Medicine, 2005. 11(1): p. 171-173.
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