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Wien Klin Wochenschr (2020) 132:260–273https://doi.org/10.1007/s00508-020-01625-w

A critical examination of themain premises of TraditionalChineseMedicine

Michael Eigenschink · Lukas Dearing · Tom E. Dablander · Julian Maier · Harald H. Sitte

Received: 9 December 2019 / Accepted: 26 February 2020 / Published online: 20 March 2020© The Author(s) 2020

Summary Traditional Chinese Medicine (TCM) con-sists of a plethora of therapeutic approaches aimingto both characterize and treat diseases. Its utiliza-tion has gained significant popularity in the westernworld and is even backed by the World Health Organi-zation’s decision to include TCM diagnostic patternsinto the new revision of the International Classifica-tion of Diseases code, the global standard for diagnos-tic health information. As these developments andpotentially far-reaching decisions can affect modernhealthcare systems and daily clinical work as well aswildlife conservation, its underlying factual basis mustbe critically examined. This article therefore providesan overview of the evidence underlying the basic TCMconcepts, such as Qi, meridians, acupuncture, pulseand tongue diagnostics as well as traditional herbaltreatments. Moreover, it discusses whether scientificliterature on TCM reflects the current standard for ev-idence-based research, as described in good scientificpractice and good clinical practice guidelines. Im-portantly, misinformation regarding the therapeuticefficacy of animal-derived substances has lead andcurrently leads to problems with wildlife preservationand animal ethics. Nevertheless, the (re-)discovery ofartemisininmore than 50 years ago introduced a noveldevelopment in TCM: the commingling of Eastern andWestern medicine, the appreciation of both systems.The need for more rigorous approaches, fulfilment of

M. Eigenschink · L. Dearing · T. E. Dablander · J. Maier ·H. H. Sitte (�)Institute of Pharmacology, Medical University Vienna,Vienna, Austriaharald.sitte@meduniwien.ac.at

H. H. SitteCenter for Physiology and Pharmacology, Institute ofPharmacology, Medical University Vienna, WaehringerStraße 13A, 1090 Vienna, Austria

and agreement to current guidelines to achieve high-quality research are of utmost relevance. Thereby, an-cient knowledge of herbal species and concoctionsmay serve as a possible treasure box rather than Pan-dora’s box.

Keywords Qi · Meridians · Acupuncture · Pulsediagnostics · Tongue diagnostics

Introduction

The origins of Traditional Chinese Medicine (TCM)date back more than 4000 years. A first written compi-lation of TCM was published as The Yellow Emperor’sInner Classic (Huangdi Neijing). This publicationserved as one of the first dogmatic sources for the ap-plication of TCM. The Huangdi Neijing comprises twobooks which contain a number of treatises reflectingon the basic and theoretical principles of TCM, as wellas its approach to diagnosis, acupuncture and thera-peutic applications. Over the millennia, the HuangdiNeijing has been annotated and revised numeroustimes; furthermore, it has been partly translated intoEnglish to make the principles and foundation ofTCM available to interested practitioners and health-care professionals worldwide [1, 2].

A first western account of TCM was published inthe eighteenth century, when the East Indian Com-pany brought both physicians and medically trainedpriests to China [3]; however, the communication be-tween the evolving western medicine and TCM wasnot exhaustive as an exchange of medicinal conceptsrarely took place. Indeed, as noted by Nakayama [4],anatomical studies and surgical operations were rela-tively uncommon in Chinese medicine because of theConfucian tenets of the sacred body. With the princi-ples of yin and yang, the five elements, the universalenergy “qi”, the meridians, the inclusion of environ-

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mental factors, such as wind, damp, hot and cold,TCM appears as a philosophy that attempts to inte-grate mind, body, health and disease prevention bydiverse practices.

The main principles of TCM have evolved overthousands of years and TCM practitioners also referto this vast and longstanding experience as a sealof trust. TCM’s fundament is based on its holisticview, the principle of harmony, individuality, and theprevention and treatment of disease. Following theseprinciples, TCM uses unique diagnostic and thera-peutic techniques, such as acupuncture, Tai Chi andQi Gong as well as a plethora of plant and animalderivatives to restore health and prevent illness.

After World War II, a TCMmodernization campaignwas set up: the leaders of “New China” put majorefforts into founding universities, hospitals and re-search institutes for the promotion of TCM [5]. Thefirst phase led to a rapid increase in popularity andgeneral importance of TCM, resembling a harbingerfor the larger changes that were about to follow. Thesecond phase was heralded in the 1980s by Deng Xi-aoping’s implementation of the Chinese economic re-form, leading to the consolidation and continuousgrowth of national networks as well as the beginningof international recognition. Nonetheless, the acmewas reached during the third phase: in 2015, You-you Tu was awarded the Nobel prize for the discov-ery of artemisinin [6]. Furthermore, TCM diagnosticpatterns were included into the 11th revision of the In-ternational Classification of Diseases1, which was ac-cepted by the WHO on 25 May 2019 and will comeinto effect on 1 January 2022.

We ascertained evidence in the field of TCM on thebasis of the following topics: (i) TCM publications,(ii) TCM diagnostics, (iii) meridians and acupuncture,and (iv) TCM remedies. It was our intended goal toexamine the most obvious and publicly visible ones.

First, we evaluated the increase in publication ratesrelated to TCM, using data derived from the publiclyavailable database PubMed2. Then, we searched forhighly cited TCM literature and analyzed their contentfor logical reasoning and scientific justification. In or-der to elucidate the quality of published articles weperformed a substantive analysis of the 100 most citedTCM publications available on PubMed. By using thesoftware Publish or Perish (Harzing, London, UK) wewere able to constrain the publications between 2015and 2019. Next, we assessed TCM’s most commonlyapplied diagnostic tools—tongue and pulse diagnos-

1 WorldHealth Organization: WHO. ICD-11 International Classi-fication of Diseases in 11th revision. (homepage on the internet;accessed Dec. 02.2019); available from: https://icd.who.int/en2 PubMED is a database of the National Center for Biotechnol-ogy Information (NCBI), a division of the National Library ofMedicine (NLM) at the National Institutes of Health (NIH) of theUnited States of America, accessible via the URL: https://www.ncbi.nlm.nih.gov/

tics: it is believed by TCM practitioners that the in-terior of the human body is connected to its exteriorand therefore, tongue and pulse diagnosis serve asreference points to determine pathological changeswithin the organism. TCM views the human bodyas a holistic unit where all parts are connected byso-called channels and collaterals, the meridians, inwhich the vital force Qi is believed to be distributedthrough the entire body. Qi has its roots in a philo-sophical theory, first described in The Analects of Con-fucius [7]. The meridian system historically consists of12 main meridians and, while subjected tomany stud-ies, has remained unmodified throughout the last twomillennia [8]. The rationale behind acupuncture treat-ment builds on the philosophical foundations of Qiand themeridians, which has been controversially dis-cussed since its inception. Nevertheless, acupunctureis a widely known and broadly applied TCM method,and therefore we discuss arguments regarding its effi-cacy, safety and utilization.

Historically, the therapeutics used in TCM derivefrom the Guidelines and details of materia medica (=Bencao gang mu), a book published during the Mingdynasty by the Chinese herbologist Li Shizhen. TheBencao gang mu describes approximately 11,000 dif-ferent therapeutics and contains information about1892 herbal remedies [9, 10]. Whilst mostly focus-ing on herbal remedies, evaluating their therapeu-tic potential and risk for pharmacointeractions, wealso tried to provide a brief overview about ethicalconsiderations regarding the utilization of therapeu-tics, deriving from endangered species such as therhinoceros and the pangolin [11, 12]. The utilizationof these products, their inhumane production condi-tions (e.g. retrieval of bear gall), as well as the vio-lation of the Convention on International Trade in En-dangered Species of Wild Fauna and Flora have beenmatters of recent animal welfare debates [13, 14].

The critical analysis of TCM, its historical back-ground and philosophical basis also encouragedus to evaluate our own, western, evidence-basedmedicine (EBM). This was insofar of importance, as(i) we needed to compare TCM to “our” science-based medicine, (ii) it broadened our view for weak-nesses in our own medical system and (iii) led usto ascertain the evolution and development of EBMover time. Historically, Scotsman George Fordyceproposed the combination of evidence and medicinein the middle of the eighteenth century; however, thefirst clinical studies were conducted in 1747 by an-other Scottish doctor, James Lind, who examined theuse of vitamin C in scurvy in a systematic manner; theHungarian Ignaz Semmelweis solved the etiology ofchildbed fever roughly 100 years later [15]. Lind, Sem-melweis and others in succession converted empiricalobservation into clinical studies and logical decisionmaking. The development of EBM has undoubt-edly also been propelled by major crises as causedby tetanus-contaminated diphtheria antitoxin serum

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and the toxic ingredients in Elixir Sulfanilamide inthe United States of America [16] and the phocomeliacaused by the hypnotic drug thalidomide in Germanyand other countries [17]. As a result, rigorous drugtesting was implemented as both the American Foodand Drug Association and the European MedicinesAgency were strengthened in their efforts to preventharm from medicinal products on their way to themarket. This endeavor also strengthened EBM sincethe drugs under scrutiny have to demonstrate efficacyin their clinical target population. Yet, unresolved is-sues are still present in EBM; however, its approachand ongoing rigorous evolution is unprecedented andwithout alternative.

Importantly, similar to the development and evolu-tion that EBM went through, TCM also started a pro-cess of change and evolution: this process can begauged with the increasing amount of clinical stud-ies on TCM therapeutics; studies, however, have yetto meet the modern standards described in good clin-ical practice (GCP) and good scientific practice (GSP)guidelines. To date, the theoretical foundation laidout by the Taoist Confucian philosophy still remainsand is deeply embodied and supported by the Chinesegovernment. This political involvement even leadsto the aforementioned implementation of TCM diag-noses into WHO publications [13].

Quantitative and qualitative analysis of TCMpublications

Information about the quality, quantity, and origin ofpublished TCM articles was examined in the publiclyaccessible database PubMed: research trend visual-izations were performed with the objective of ana-lyzing alterations and developments in TCM publish-ing frequencies. Accordingly, TCM publication rateshave risen almost exponentially throughout the past30 years, with 8780 published articles in 2019 marking

Fig. 1 Visualization of publication numbers for the medi-cal subject headings (MeSH) search term Traditional Chinesemedicine. The inquiry was conducted on 28.10.2019 usingthe National Institute for Biotechnology Informations (NCBI)PubMed database. A timeframe was set, ranging from 1966to 2019

the highest number ever of published TCM articles(Fig. 1).

Next, we used the software Publish or Perish [113]to obtain 948 articles registered in Google Scholar3

including the keyword Traditional Chinese Medicine,published within the timeframe 2010–2020, to iden-tify the publisher with the highest number of TCMarticles. We performed a quantitative analysis accord-ing to the workflow summarized in Fig. 2a. A totalof 101 journals were considered with 11 journals ac-counting for more than 70% of all published articles,a total of 672 publications. Interestingly, Elsevier hadthe highest number of published TCM articles in thepast 10 years (Fig. 2b). In total, Elsevier, Hindawi,Springer and the China National Knowledge Infras-tructure (CNKI) accounted for approximately 50% ofall published articles.

Furthermore, an analysis of the 100most cited TCMpublications registered in Google Scholar4 was per-formed. The data were retrieved similarly to the anal-ysis of journal publication frequencies and adjustedfor exclusion criteria (Fig. 2a). Subsequently, the arti-cles were ranked according to a binary point system toascertain the overall quality of the publications. Thepoint system consisted of three major areas: “overallwording”, “argumentative patterns” and “use of clas-sical fallacies”. As shown in Fig. 3a, these three hyper-nyms were divided into a total of 13 sub-areas, eachresembling a different type of distorted scientific argu-mentation. If one of these argumentative patterns wasused within the title or abstract of an article, 1 pointwas assigned to the publication—making 13 pointsthe highest possible score. Furthermore, the articleswere clustered, forming four different groups. Resultsare shown in Fig. 3b. Moreover, a detailed frequencyanalysis of the 13 predetermined argumentation pat-terns is provided in Fig. 3c.

However, we are aware of the fact that even thoughour approach was predefined, assigning the pointsstill remains subjective. Because of this limitation thedata provided cannot be viewed as a definite, objec-tive examination.

The search was then extended from titles and ab-stracts to complete pieces of text in order to furtherelucidate the utilization of unscientific writing pat-terns. Thereby, several writing patterns frequentlyfound in TCM publications were determined. Thesepatterns mostly resemble argumentative tools used tosubstantiate statements in an arguably nonscientificway, thus violating the rules of The European Code ofConduct for Research Integrity, published in 2011 bythe European Science Foundation4. Whilst some au-thors used naturalistic forms of argumentation such

3 https://scholar.google.com4 European Science Foundation, All European Academies: TheEuropean code of conduct for research integrity; 2011 (PDF onthe internet; accessed on Dec. 02.2019); available from: https://allea.org/code-of-conduct/

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Fig. 2 a Flow chart demonstrating our approach to quantita-tive and qualitative analysis of TCM publications. All informa-tion was obtained using the programPublish or Perish utilizingthe Google Scholar database. The inquiry was conducted on02.03.2019 and 28.10.2019. b Results of the examination of

TCM article publishers with more than 20 articles uploadedon Google Scholar. The data were obtained according to themethodology described in (a). The absolute numbers havebeen sorted by the particular publisher and are shown abovethe bars

as “herbal remedies are generally better tolerated thansynthetic medications” [18], others aided themselveswith appeals to tradition or history, e.g. “The Chinesefolklore described it as ‘vegetable for long life’ and ithas been used for thousands of years in traditional

Chinese medicine” [19] or “Since prehistoric times,humans have used natural products, such as plant,[. . . ] to alleviate and treat diseases” [20]. A differ-ent pattern of reasoning frequently found in TCMpublications is the “general usage” argument; e.g.

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Fig. 3 a Criteria underly-ing our predefined binarypoint system used to eval-uate the quality of the 100most cited TCM publica-tions. If an article met thecriteria of one of the sub-areas defined above, onepoint was assigned to thepublication. b Results ofour frequency analysis ofunscientific argumentationpatterns. The data wereobtained according to themethodology displayed inFig. 2a. Articles were clus-tered according to the num-ber of scientific fallaciesobserved. Each columnrepresents the number ofarticles included in the re-spective cluster. c Resultsdepicting the frequencyof each unscientific argu-mentation pattern observedin the analysis of the 100most cited TCM publica-tions. Data were obtainedaccording to the methodol-ogy provided in Fig. 2a.

Overall wording

• Exaggera�on• Lack of objec�vity• Blaming "Big Pharma"• Non-scien�fic wording

Argumenta�ve pa�erns

• Emphasizing superiority• Emphasizing

importance• Pressing for research• Distor�on of facts• Defini�sm

Classical fallacies

• Appeal to authority• Appeal to tradi�on• Persis�ng on be�er

tolerance• Naturalis�c

argumenta�on

a

b c

“Traditional medicines, especially herbal or botanicmedicines, are very important in health care systemsaround the world.” [21].

Although some of the aforementioned assertionsmay sound promising and definite, as well as the factthat discovering and utilizing the medicinal proper-ties of plants will also continue to be an importantresource in the future [22, 23], these claims are notsubstantiated by high quality clinical studies. Approx-imately 56% of TCM studies uploaded on clinical-trials.gov constitute a sample size of fewer than 100subjects or lack statistical power. Furthermore, thesestudies are prone to statistical type 2 errors [24], there-fore less likely to reject a wrong null hypothesis [25]:this imprecision in study design can lead to seriousmisinformation regarding e.g. clinical endpoints mea-sured in interventional trials.

Despite rising registration rates in ClinicalTrials.govto more than 10 entries/month and over 570 studiescompleted (45% of all entries), only 50 TCM studies,a total of 9% have reported results [24]. In contrast,more than 50% of conventional drug trials marked ascompleted on ClinicalTrials.gov reported results [26,27]. Such inaccuracies constitute a fertile soil for theusage of unconventional and unscientific argumen-tation patterns, especially when considering the highrisk for type 2 errors and the reporting bias. In gen-eral, the methodological quality of clinical trials was

reported to be rather low: as can be seen in the lit-erature evaluating the efficacy of TCM medications inthe treatment of cardiovascular diseases [28].

Considering nearly exponentially rising publicationrates, the need for awareness regarding GSP and GCPis urgent and obvious. Multiple agendas, based onthe four elemental concepts of research: honesty, ac-countability, professional courtesy and fairness, andgood stewardship, have been published on the WorldConferences of Research Integrity throughout the pastyears, aiming to provide guidelines for modern stateof the art research and dissemination [29]. With re-spect to clinical trials, GCP guidelines are readily avail-able, regularly updated and even partly implementedin legislation5. Many of the aforementioned TCM pub-lications ignore these common scientific conventionsthat are based on GCP and GSP guidelines. There-fore, they constitute a source for misinformation re-garding complex research topics, such as the evalua-tion of traditional herbal therapies. Moreover, fallaciesand unconventional argumentation patterns will con-tinue to undermine the development ofmore credible,

5 Committee for HumanMedicinal Products: Guideline for goodclinical practice Edition 6; 2016 (PDF on the internet; Accessedon Dec. 02.2019); available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-6-r2-guideline-good-clinical-practice-step-5_en.pdf

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valuable research. An example for underdeveloped re-search standards is publications attempting to provethe existence of Qi and the meridians.

Meridians: more than a philosophical concept?

The concept of Qi, the so-called breath or force oflife, is a philosophical theory dating back over 3500years and establishes the basis for most TCM theories[18]. The Qi is believed to flow in certain pathways,so-called meridians, which were first described in theHuangdi Neijing [1, 2, 8, 30]. The meridian systemhistorically consists of 12 main meridians and has vir-tually remained untouched throughout the last twomillennia6. In order to provide evidence for the exis-tence of meridians, several anatomical, physical andbiochemical studies have been conducted; many ofwhich violate the European Code of Conduct for Re-search Integrity and the aforementioned GSP guide-lines.

In an effort to anatomically locate meridians,a French research group led by de Vernejoul appliedradiotracers to acupuncture points in a number ofseparate experiments [31–33]. Thereby, emission pat-terns were acquired and the authors concluded themto match the classical description of TCM meridians[33]. In addition, the authors reported that only 5%of the applied radiotracer was measurable migrat-ing along blood or lymph vessels [33]. Nevertheless,Guiraud et al. failed to reproduce de Vernejoul’sresults [34]. In stark contrast, Guiraud et al. evenfound the emission patterns to match normal vascu-lar drainage [34]. Furthermore, no difference betweenradiotracer application on acupuncture points andcontrol points was detectable [34].

A different approach to scientifically validate theexistence of meridians relies on changes in electricalconductivity between acupuncture points and controlpoints [35–37]. Publications utilizing this techniqueoften include inaccuracies concerning the way infor-mation about the applied methodology is presented.Furthermore, the number of study participants wasrather small in most of the publications and the mea-surements did not conclusively show a difference inimpedance in all subjects at all acupuncture points[36, 37].

In addition to the biophysical characterization ofmeridians and acupuncture points, anatomical andstructural equivalents have also long been sought af-ter. Historically, meridians have been described to fol-low the so-called vascular nerve bundle [38]; howeverrecently, Maurer et al. dissected four cadavers and two

6 WHO Scientific Group on International Acupuncture Nomen-clature & World Health Organization: A proposed standard in-ternational acupuncture nomenclature: report of a WHO scien-tific group; 1991 (Homepage/PDF on the internet; accessed onDec. 02.2019); available from: https://apps.who.int/iris/handle/10665/40001

lower limbs concluding that meridians and acupunc-ture points could be related to the fascia corporis ex-terna, muscles, nerves and tendons and to only bemerely intertwined with vascular nerve bundles [39].Therefore, without providing proper evidence for theirexistence, the authors described an abundance of su-perficial anatomical structures as a possible anatom-ical correlate for meridians [39].

Taking publications in these different fields ofmeridian research into consideration, no scientifi-cally viable explanation for the existence of meridiansin a non-philosophical context has been established.Moreover, many studies lack methodological qualityand are prone to reporting bias [31–33, 35–37, 39].

Acupuncture—about popular usage andquestionable effect sizes

The use of acupuncture for the treatment of diseaseis based on the aforementioned rather philosophi-cal, nonscientific concept of Qi and the meridians[40]. Evidence for the use of acupuncture has allegedlybeen reported as early as 6000 B.C. but remains highlycontroversial [8]. Acupuncture is widely known andused on a global scale. It is suggested by 90% ofAmerican cancer institutes, offered on-site by 70% asa treatment for common chemotherapy side effects[41] and actively asked for by patients as a treatmentfor migraine [42], musculoskeletal disorders [43] andallergies [44]. Nevertheless, comprehensive reviewscontaining facts regarding its efficacy, safety and so-cioeconomic utilization as well as properly conductedclinical studies are barely available, as can be seenfrom the following examples:

Migraine is the third most common disease in theworld [45]. It is a painful burden to many people;time spent in the ictal state is exhausting, making mi-graine the leading cause of disability in patients withneurological diseases [45]. Although conventionaltreatment options are widely available, acupunctureis often additionally used to relieve symptoms [46].A Cochrane review published in 2016 comparingacupuncture therapy to a non-interventional controlgroup, showed moderate evidence for its usage inthe reduction of migraine frequency. The authorsalso concluded that acupuncture was non-inferiorto prophylactic drug treatment, however, only in theshort-term follow-up setting [42]. Besides that, onlysmall effects of acupuncture over sham treatmentwere detectable. Despite these seemingly promisingassertions, due to an up to 50% risk for attrition andselection bias, the results have to be taken with a grainof salt [42].

With a 4–33% prevalence, lower back pain is themost common musculoskeletal disorder [47]. Eventhough it was named as the origin for most yearslived with disability in 2016 [48], its cause remainsunknown in up to 95% of the cases [49]. Therefore, de-spite receiving conventional pharmacological therapy,

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patients tend to seek alternatives, such as acupunc-ture, for symptom relief. A meta-analysis of shamcontrolled clinical trials showed that acupuncture hada moderate effect over sham acupuncture in pain re-duction and no effect on disability reduction [43]. Fur-thermore, the high levels of heterogeneity observed inthe studies included were determined to have origi-nated from sham needle location/depth and insuffi-cient selection of study participants [43].

Allergic rhinitis affects 10–25% of the world’s pop-ulation [50], causing a significant decrease in worktime productivity and overall quality of life [51]. Theeffect of acupuncture on the severity of symptoms andquality of life in patients with allergic rhinitis and itsefficacy in the modern clinical environment largelyremains controversial. While some studies reportedan effect with possible clinical implications [44], sys-tematic reviews remain inconclusive on whether thereported results are sufficient for acupuncture’s clini-cal implementation in the therapy of allergic rhinitis[52, 53].

In order to evaluate the biochemical mechanismsunderlying acupuncture treatment, an abundance ofpreclinical studies have been conducted throughoutthe past centuries [54]. Functional magnetic reso-nance imaging studies have indicated that acupunc-ture causes somatosensory, affective and cognitiveresponses; furthermore, there is moderate evidencefor acupuncture’s ability to modulate specific brainareas [55]. Moreover, in the search of molecules vi-able of transmitting acupuncture’s analgesic effects,adenosine as well as endogenous opioids such asbeta-endorphin and dynorphin have been suggested[56]. Adenosine was shown to be released duringacupuncture therapy in a mouse model, activatingGi-coupled A1-adenosine receptors, ultimately lead-ing to analgesia [57]. Endogenous opioids were shownto be present in enhanced concentration in the cere-brospinal fluid of patients treated by acupuncture[58]. Furthermore, these findings are supported bythe fact that transferring the cerebrospinal fluid ofa rabbit that had previously undergone acupunctureto a different, control rabbit led to analgesic effectsin this animal; effects that were diminishable bynaloxone [59]; however, the experimental data pro-vided in this paragraph only resembles a fragment ofthe preclinical research performed to elucidate thephysiological mechanisms underlying acupuncturetreatment. Therefore, it has to be mentioned thatcritics noted most of the research was done in China,negative results may not have been published andsome of the experiments could not be replicated [60].

A frequently occurring issue regarding reviews andmeta-analyses about acupuncture is the incoherentcontrol group design of included primary studies.While solutions for the problem of double blinding,such as masked non-penetrating needles exist [61,62], the validation of effects using sham acupunc-ture remains questionable [63]. Studies have shown

that sham acupuncture effects tend to exceed nor-mal placebo-controlled effects. Moreover, penetrat-ing sham needles obtain the most similar resultswhen compared to conventional acupuncture ther-apy, therefore reducing effect sizes [64]. Furthermore,evidence suggests that effects of acupuncture maynot be specific for the acupuncture point [65, 66].

In order to correctly assume effect sizes, researchersmight consider using more than one type of controlscenario such as acupuncture point-specific and non-acupuncture point-specific penetrating/non-pene-trating control in a double-blinded manner. Nonethe-less, conventional acupuncture therapy was shown tobe superior compared to all previously mentionedcontrol designs in the treatment of chronic pain [64].

Concerning the safety of acupuncture, only fewhigh-quality data are available. A systematic reviewpublished by Chan et al. in 2017 showed analyzedstudies lacking in a priori design and sufficient fol-low-up periods; thus, these studies were not able toscreen minor events. Additionally, the majority ofthe analyzed data were case reports. Even thoughorgan or tissue injuries, infections and local eventswere reported, severe adverse effects seemed to occuronly rarely; however, case control studies ought to bedone to further investigate the frequency of adverseeffects, determine causes and improve the quality oftreatment [67].

Taking the aforementioned considerations into ac-count, acupuncture shows some effect in the treat-ment of diseases like migraine, lower back pain andallergic rhinitis; however, there is no conclusive sci-entific basis for its mode of action. Moreover, due tothe problem of control group design and the resultingheterogeneity of primary studies included in system-atic reviews and meta-analyses, reported effect sizesmust be considered with care.

The need for high quality data obtained by carefullyconducted studies does not only concern therapeu-tic approaches like acupuncture. In order to providean adequate therapy, diagnostic methods have to bethoroughly tested and evaluated too.

TCM diagnostics—first, check your own pulse

In the clinical use of TCM great emphasis is placedon the principle of diagnostics. The average durationof a TCM consultation is 9min longer than that ofa general practitioner. Therefore, studies indicatedthat patients treated by TCM practitioners tend tohave higher levels of satisfaction [68]. In TCM, a di-agnosis is established by combining the principles ofinspection, auscultation, olfaction, inquiry and palpa-tion, ultimately creating a so-called pattern diagnosis[69]; however, publications have suggested TCM pat-tern diagnosis to be subjective to a certain degree:When evaluating its efficacy, the observed level of re-liability may be insufficient [70].

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In order to provide information about the clinicaleffectiveness of a diagnostic procedure, scientists usu-ally evaluate its inter-rater and intra-rater reliability.Whilst inter-rater reliability refers to the objectivity ofa diagnostic method, intra-rater reliability quantifiesits reproducibility.

Multiple studies investigating the accuracy of TCMdiagnostics concerning diseases such as lower backpain (LBP) [71], chronic headache [42] and rheuma-toid arthritis [72] have been performed. The authorsfound significant variability in TCM pattern diagnosesand selection of acupuncture points. Moreover, lowlevels of inter-rater agreement between TCM practi-tioners were noted. The observed heterogeneity inestablishing the right pattern diagnosis and the differ-ences in symptom interpretation pose a challenge tothe implementation of standardized therapeutic ap-proaches. In order to propose an adequate therapy,the diagnostic process needs to be rigorously exam-ined. In the following, two diagnostic tools specificto TCM will be highlighted as examples: pulse andtongue diagnosis.

Pulse examination marks a cornerstone of TCMdiagnostic principles; it is sometimes even referredto as the most important diagnostic approach inTCM. While the pulse characteristics of a patient maychange due to systemic events, such as sepsis or car-diovascular diseases, the utilization of pulse palpationas a viable method for the detection of pregnancy, al-though described in TCM publications [73], remainshighly questionable and is not supported by a broadbasis of research. Moreover, the lack of evidence andstandardization is also apparent in the pertinent liter-ature concerning TCM diagnostics [74]. Even thoughrecently published articles usually addressed this lackof standardization resulting from the utilization of de-scription patterns that originated more than 500 yearsago, viable alternatives for this outdated and ratherphilosophical categorization are hardly to be found.For instance, pulse is referred to as “. . . a light knifescraping bamboo, [. . . ] a diseased silkworm eatinga leaf” [75]. Moreover, articles include questionablestatements such as: “tcm doctors are accustomed toassessing pulse by their own perception, rather thanon a rational basis” [74].

Additionally, the diagnostic value of pulse exami-nation has been challenged by a study of Walsh et al.in which TCM students were asked to identify basicparameters, such as speed, depth, volume, length andquality of the pulse. The overall agreement level didnot differ from that expected by chance alone. Nev-ertheless, the authors proceeded to conclude that in-adequacies in the pertinent literature, the quality ofteaching and insufficient clinical practice caused thelack of objectivity, not the reliability of pulse diagnos-tics itself [76].

In addition to pulse palpation, tongue diagnosisconstitutes another hallmark of TCM diagnostics. Byevaluating characteristics, such as cracks, color and

coating, TCM practitioners try to assess the currenthealth state of, for instance, corresponding internalorgans. Even though it seems plausible that a patient’stongue can exhibit certain characteristics, hinting ateither localized diseases, such as oral candidiasis [77]or systemic diseases, such as Sjögren syndrome [78],the evaluation of complex clinical issues is not backedby a broad spectrum of high-quality literature. Fur-thermore, studies assessing the efficacy of tongue di-agnostics found low levels of inter-rater reliability. Forinstance: a publication by Lo et al. [79] featuring12 TCM practitioners evaluating a total of 20 patients,found tongue diagnostics to lack inter-rater reliabil-ity in key areas: The agreement amongst different ob-servers regarding characteristics, such as tongue color,tongue spots and saliva was reported to be moderate.Moreover, exchange between practitioners did not im-prove overall agreement [79].

Additionally, in a study conducted by Kim et al. 10realistic tongue depictions were presented to 30 TCMpractitioners in order to assess the subsequent diag-nostic consistency. Again, a low inter-rater and intra-rater agreement was found amongst the participants[80].

Research regarding TCM diagnostic methods is stillin its infancy. Consequently, the lack of high-qualityliterature posed a challenge to the evaluation; how-ever, it was apparent that authors who assessed theobjectivity and reproducibility of TCM diagnosticsunanimously agreed that the principles underlyingthese examinations need to be standardized in orderto fit the modern understanding of medicine. Sub-sequently, the inclusion of metric data derived fromobjective biochemical markers is imperative. More-over, parameters, such as sensitivity, specificity as wellas positive and negative predictive values, ought to beevaluated in order to objectify TCM diagnostics andbe able to compare their efficacy to western diagnosticmethods. Following these thoughts, TCM diagnoseswould first have to be objectively and clearly defined.

TCM therapeutics—forgotten treasure orPandora’s Box?

The TCM therapeutics historically derive from the“Guidelines and details of materia medica” (= Bencaogang mu), a book published during the Ming dynastyby Chinese herbologist Li Shizhen. The Bencao gangmu describes approximately 11100 different thera-peutics and provides information about 1892 herbalremedies [9, 10]. Nowadays, information about TCMmedicinal products are included in the “ChinesePharmacopoeia” published in 2015 [81]: it was es-tablished in 1950 by the Chinese Health Ministry asan official document that is now listed on the WHO“Index of Pharmacopoeias” [82]. It comprises a totalof 5608 medicinal products and covers more than90% of TCM medications, including herbal remedies,animal-derived products, minerals, food and conven-

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tional drugs7. Henceforth, the Chinese governmentdeclared the development, utilization and interna-tional promotion of TCM as one of their eight stepstowards a healthier China8.

Regarding the usage frequency of TCM withinChina, it is estimated that more than 100 millionpeople use traditional medicine every year [83]. Thispopularity is also met by a continuous increase inthe demand for rural areas to cultivate herbs used inTCM. In China alone, it is believed that this demandwill rise from 2.3 million hectares of land to an es-timated 4.4 million hectares in 20259 [84]. The TCMproducts are mainly exported to Asian countries, theUSA and Europe; however, China also imports enor-mous amounts of herbs, predominantly from Asiancountries9 [85]. Similarly, this continuous growth canalso be observed with increased demand for animalproducts. These circumstances pose a great challengeto wildlife preservation and animal ethics9. Moreover,the market for products derived from endangeredspecies such as rhinoceros, bear, tiger, lion and pan-golin gained popularity in Asia, especially in China,despite persistent trade bans and harsh penalties fortheir violation since 1993 [11].

Amongst many other therapeutics described in theBencao Gangmu, rhinoceros horn and its derivativesremain one of the most controversial ones. Whilerhinoceros horn derivatives have officially been ex-cluded from the Chinese pharmacopoeia, studies haveindicated that they are still in use for the treatmentof medical conditions such as fever, convulsions andpain10. This also coincides with reports published bythe International Union for Conservation of Nature(IUCN) Species Survival Commission in 2019, indicat-ing China and Vietnam to be the main destinationsfor rhinoceros horn trafficking11.

7 Chinese Pharmacopoeia Commission ICP05016748: ChinesePharmacopoeia; [81] (Homepage on the internet; accessed onDec. 08.2019); available from: http://wp.chp.org.cn/en/content.html?id=ff8080814fd5ba0a014fd6f0402c01438 13thfive-year plan for economic and social development of thePeople’s Republic of China.9 Department of Market Order—Ministry of Commerce: 2017Chinese herbal medicine circulationmarket analysis report; 2018(PDF on the internet; accessed on Dec. 08.2019); available fromhttp://images.mofcom.gov.cn/sczxs/201806/20180626165603110.pdf10 Natural Resources Defence Council (NRDC), Horizon Key,Kennaugh, A.: Rhino rage: what is driving illegal consumer de-mand for rhino horn; 2015 (PDF on the internet; accessed onDec. 08.2019); available from http://www.rhinoresourcecenter.com/index.php?s=1&act=refs&CODE=ref_detail&id=147790879011 Milliken T, Emslie RH, Talukdar B.: African and Asianrhinoceroses–status, conservation and trade. A report fromthe IUCN Species Survival Commission (IUCN/SSC) African andAsian Rhino Specialist Groups and TRAFFIC to the CITES Sec-retariat pursuant to Resolution Conf (Vol. 9). 2009 (PDF on theinternet; accessed on Dec. 08.2019) available from: https://www.cites.org/sites/default/files/eng/cop/15/doc/E15-45-01A.pdf

Despite seizure numbers due to rhinoceros horntrafficking still rising throughout the past 10 years, theanswer to the question onwhere this illegal trade takesplace remains somewhat enigmatic; however, sinceevidence does not implicate conventional pharmaciesto take part in the trafficking, it is therefore believedthat most of the transactions take place on social me-dia platforms and in the dark net12.

Apart from the prominently featured rhinoceros,the survival of more extraordinary species such asthe pangolin or scaly anteater is also directly affectedby TCM. Pangolins are mammals of the order Pholi-dota and represent the most trafficked species in theworld. They are directly threatened by extinction be-cause of their use for medical purposes [86]. In con-trast to official bans issued on the therapeutic usageof rhinoceros horn and tiger bones, the use of pan-golin claws and scales in the treatment of coronaryheart disease, myocardial infarction and stroke is of-ficially permitted by the Chinese government and in-cluded in the Chinese pharmacopoeia [87]. Moreover,there are approximately more than 200 pharmaceuti-cal companies producing more than 60 different typesof pangolin derivatives, prescribed in about 700 Chi-nese hospitals [87]. Taking seizure reports into con-sideration, more than one million pangolins are es-timated to have been illegally traded within the last20 years in Asia alone [87]. China was found to be themost common trafficking destination for large quan-tity shipments of scales and claws between 2010 and201513. Thus, TCM might be considered one of thebiggest contributors to pangolin trafficking and ex-tinction.

Most recently, the Chinese government reacted andissued an official ban on the coverage of pangolinderivatives by the national insurance14. Although rig-orous actions will go into effect in 2020, a nationwideban on the trade of pangolins and the initiation of ed-ucation programs, aiming at alerting people to alter-natives to pangolin derivatives, only seem moderatelylikely [12]. Thus, the survival of the pangolin oncemore remains uncertain.

In order to cease the utilization of animal-derivedproducts in TCM, several authors have proposed

12 Nowell K.: Species trade and conservation. Rhinoceroses:Assessment of rhino horn as a traditional medicine; 2012 (Pdfon the internet; accessed on Dec. 08.2019); available from:http://www.rhinoresourcecenter.com/index.php?s=1&act=refs&CODE=ref_detail&id=138966978413 Heinrich, S., Wittman, T.A., Ross, J.V., Shepherd, C.R., Chal-lender, D.W.S., and Cassey, P.:The Global Trafficking of Pangolins:A comprehensive summary of seizures and trafficking routesfrom 2010–2015; 2015 (PDF on the internet; accessed on Dec.08.2019); available from: https://www.traffic.org/publications/reports/the-global-trafficking-of-pangolins/14 National Healthcare Security Administration: Statement onthe insurance coverage of medicinal products; 2019 (Home-page/PDF on the internet; accessed on Dec. 08.2019) availablefrom: http://www.nhsa.gov.cn/art/2019/8/20/art_37_1666.html

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herbs as substitutes15 [88]. This proposition has tobe considered carefully, as the evidence for the thera-peutic efficacy of herbal remedies utilized in TCM re-mains poor. Furthermore, potential pharmacologicalinterference with conventional drugs may be com-mon and remains poorly investigated. For instance,high quality evidence about the clinical efficacy ofPannax ginseng, Lycium barbarum and Cinnamon,the three most extensively exported Chinese herbs, ispractically non-existent [89–91]. Moreover, a compre-hensive report of Cochrane reviews on Chinese herbalmedicines (CHM) suggested that only 16% of all in-cluded primary studies use adequate sequence gen-eration. Furthermore, only 7% of these randomizedcontrolled trials applied allocation concealment [92].Additionally, out of 51 Cochrane reviews on CHM,none were able to provide high-quality evidence nec-essary for the implementation of CHM therapies ina modern clinical environment [92]. Thus, the substi-tution of animal-derived products with well-studiedtherapeutic agents seems to be the logical conclusion.

In contrast to the well-studied mono-therapeuticsused in state of the art medical practice, CHMs mostlyconstitute a mixture of different herbs; however, onlyfew studies provide a detailed chemical analysis of thecompounds investigated. This in turn leads to unre-liable data, as adulterants and contaminants possi-bly alter both preclinical and clinical endpoints [93].Moreover, studies conducted in the late 1990s andearly 2000s have shown TCM herbal remedies to befrequently contaminated with other pharmaceuticalagents, such as phenytoin, glibenclamide or corticos-teroids, therefore, giving rise to potentially fatal in-teractions [94]. A recent publication indicates an in-crease in purity found in CHMs. Out of 123 inspectedsamples, approximately 7% were found to be con-taminated [95]. Nevertheless, the erroneous prepa-ration of TCM formulae has led to safety concerns re-garding quality standards for TCM therapeutics. Mis-takes, such as the accidental substitution of Stephaniatetrandra, a TCM therapeutic commonly known underthe name Fang-ji, with Aristolochia fangchi have led tosevere medical conditions, such as rapid progressiverenal failure [96–98] and the development of urothelialcarcinoma [99]. More recently, it has been reportedthat the main ingredient aristolochic acid, which isstill widely used, may also be linked to the develop-ment of liver cancer [100]. Similarly, neuropathies andencephalopathies observed in Hong Kong originatedfrom the substitution of CHM Gentiana rigescens withPodophyllum emodi, a plant used for the extraction ofcytostatic agent podophyllin [101].

15 Bell CM, Simmonds MS, Appiah SS, Howes MJ: Plant sub-stances as alternatives for animal products in traditionalmedicines; 2006 (PDF on the internet; accessed onDec. 08.2019);available from: https://www.researchgate.net/publication/251845716_Plant_substances_as_alternatives_for_animal_products_in_traditional_medicines

In contrast to the abovementioned cases, a multi-tude of biochemical and pharmacological studies areavailable, many of which indicate interactions withproteins relevant for drug metabolism and transport,such as cytochrome P450 enzymes [102] and ATP-binding cassette transporters [103]. There are implica-tions for the interaction of the commonly prescribedginseng and warfarin, ultimately leading to a reducedwarfarin plasma concentration, thus increasing thechance for thromboembolic events [103, 104]. Pub-lications on interactions between CHM and conven-tional drugs often lack a qualitative study design andthus, information has to be considered with caution[93, 103, 104].

This poses a challenge to clinicians who frequentlyencounter patients using over the counter CHMs,often in addition to their originally prescribed drugregimen [105]. Moreover, until 2018, the accessibilityto information regarding medicinal products used inTCM and their pharmacokinetic properties was poor.In 2018, a first attempt towards making CHM dataavailable for clinicians worldwide was made withthe introduction of the Encyclopedia of TraditionalChinese Medicine (ETCM), an online database pro-viding information on commonly used CHMs16. TheETCM comprises an abundance of data on pharma-cokinetic properties and possible herb-drug inter-ferences, e.g. cytochrome P450 enzyme interactions[106]. Nonetheless, considering the low number ofhigh-quality clinical studies, information originatingfrom this database has to be considered with care.

The Nobel Prize for the discovery of artemisininby You You Tu, a Nobel prize for TCM?

Given these obvious challenges concerning TCMmedicinal products and the lack of standardiza-tion, high-quality randomized controlled trials andeven basic pharmacological characterization, othermovements should be emphasized, which may beconsidered in a more positive light. You You Tu, thediscovery of artemisinin and the subsequent NobelPrize may serve as a perfect manifestation of howeastern and western medicine and natural sciencesystems may converge. The entire history of howartemisinin was discovered can be read in the ownwords of the Nobel Laureate [6]. The important factbehind the discovery was that the search for the newantimalaria drug started from a herbal knowledgebase established by the Chinese ancestors; however,it needs to be highlighted that a drug discovery pro-cess was applied and successfully completed: thecompound, isolated from an extract of the herb Qing-hao, used for more than 2000 years against malaria,was thoroughly tested in animal models, clinical tri-als and chemically characterized with all necessary

16 http://www.nrc.ac.cn:9090/ETCM/

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structure activity/efficacy studies [6]. Importantly,the initial screening failed to produce positive results.Success was only achieved after taking the historicallydescribed procedure for the preparation of Qinghaointo account, which yielded an effective and ancienttreatment commodity for Plasmodium infections forcenturies. The promising observations made in theseinitial studies received highly positive and enthusias-tic response on a global scale. This success was theresult of an opening of Chinese research to westernnatural scientific approaches, materialized in form ofthe Institute of Chinese Materia Medica which—since1983—was the designated place “for professionalswith a modern (western) medicine training back-ground” [6]. Consequently, You You Tu received theLasker DeBakey Clinical Research Award in 2011 andthe Nobel Prize for Medicine or Physiology in 2015 forher outstanding contribution as a scientist. It is alsosafe to conclude that the discovery of artemisinin andits derivatives can be viewed as a highlight of phar-macognosy, pharmacy and pharmacology; however,some authors of TCM literature utilized this break-through discovery to justify their own, in part non-scientific argumentation: “The award of the 2015 No-bel Prize in Physiology or Medicine [. . . ] brought thegreatest pride and optimism to the natural productcommunity worldwide. [. . . ], we are surely enteringa New Golden Age of natural products drug discov-ery” [107]. This statement can only be hoped to bea positive indicator for future directions and thatthe example of the artemisinin process is exemplaryfor follow-up studies and developments. Meanwhile,artemisinin and its derivatives have also been foundto possess anticancer activity, meaning they are onthe stairways to the clinics also in areas other thanmosquito-borne infectious diseases [108]. Further-more, TCM has also been explored in rheumatoidarthritis and some effects were considered to be wor-thy of further exploration [109]: the Chinese herbformulation Du-Huo-Ji-Sheng-Tang was found to im-prove lymphatic dysfunction in a transgenic mousemodel over-expressing the abundant inflammatorycytokine TNF-A [110]. Ferulic acid has subsequentlybeen determined as its most active ingredient andshown promising pharmacodynamic effects in lymphvessel drainage and contraction [111].

Conclusion

The utilization of TCM is based on a vast history dat-ing back thousands of years, thereby justifying theword “traditional” in its title. It is well known in centralEurope and its usage, even though hardly backed byscientific studies, enjoys general acceptance amongstthe population17. This review aimed on examining

17 Unpublished data about the usage patterns and popularity ofTCM in Austria (survey conducted in 2019).

a number of important areas of TCM covering Qi,meridians, acupuncture, pulse and tongue diagnosticsas well as herbal remedies. Furthermore, the publica-tion frequency of TCM literature and the argumenta-tive patterns found in the top cited publications wereanalyzed. It was observed, that most publicationsused fallacious descriptions or expressions to substan-tiate their argumentation. Moreover, it was impossi-ble to determine a scientifically justified basis for theexistence of Qi and the meridians; hence, it is diffi-cult to reconcile how acupuncture works as it is basedentirely on finding the right acupuncture point; how-ever, there are measurable improvements albeit theevidence can only be graded as mild. It has been spec-ulated that nervous stimulation by short-term paininduction or psychological interference may be theunderlying reason for acupuncture effects to occur.Furthermore, an exploration of Tai Chi in comparisonto other mobility programs in Parkinson’s disease andother disorders has more recently drawn considerableattention [112]. These TCM-based interventions ap-parently improve the patient’s ability to move in a re-producible way; however, this cannot be ascertainedin many other areas of TCM: The standardization ofherbal remedies is difficult to achieve. Moreover, theusage of questionable ingredients deriving of specieson the brink to extinction, and the high variabilityof diagnostic procedures in TCM do not consolidatefaith [70]. The transition to science-based diagnosticmethods also largely depends on the ability to imple-ment scientific principles, as provided in GSP guide-lines, as fundamental parts in the evaluation of di-agnostic tools. Furthermore, with TCM diagnosis cri-teria getting implemented in the 11th revision of theInternational Classification of Diseases which will beactively used by clinicians around the world by Jan-uary 2022, the safety and efficacy of TCM therapeuticshas to be put to the test18 [13, 14]. It remains unclearwhether this development, which adds traditional eth-nomedicine to the armamentarium of clinicians, canbe justified over a longer perspective [13]. Further-more, it needs to be clarified whether social securityand healthcare systems will be able to financially copewith the newly implemented “traditions”.

Acknowledgements We are grateful to Luise Bellach, CoraDearing and Edzard Ernst for comments on the manuscript.

Funding Openaccess fundingprovidedbyMedicalUniversityof Vienna.

Conflict of interest M. Eigenschink, L. Dearing, T.E. Dab-lander, J. Maier and H.H. Sitte declare that they have nocompeting interests.

Open Access This article is licensed under a Creative Com-mons Attribution 4.0 International License, which permits

18 World Health Organization: ICD-11 Implementation or Tran-sition Guide, Geneva; 2019 (PDF from the internet; accessed onDec. 08.2019); available from: https://icd.who.int/docs/ICD-11%20Implementation%20or%20Transition%20Guide_v105.pdf

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use, sharing, adaptation, distribution and reproduction inanymedium or format, as long as you give appropriate creditto the original author(s) and the source, provide a link tothe Creative Commons licence, and indicate if changes weremade. The images or other third party material in this articleare included in the article’sCreativeCommons licence, unlessindicated otherwise in a credit line to thematerial. If materialis not included in the article’s Creative Commons licence andyour intended use is not permitted by statutory regulation orexceeds the permitted use, you will need to obtain permis-sion directly from the copyright holder. To view a copy of thislicence, visit http://creativecommons.org/licenses/by/4.0/.

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