Written by Bahula Roy Upton
One of the points of demarcation between the basis of evidence by which traditional and modern drugs are differentiated is empirical observation of the former and modern clinical trials of the latter. Interestingly, as in the examples of toxicity and fraud discussed above, it is only when approved drugs get into empirical use are their actual toxicity revealed. Additionally, in the US, 20% of prescription drugs are used for off-label uses, uses for which they were not specifically approved, including use in pregnancy and in children, uses for which were determined by practitioners empirically and are legally allowed. A 2006 study reported that most all of these off-label uses (73%) had little or no scientific support (Radley et al. 2006). This is most troubling as one of the primary reasons given worldwide that dissuades physicians and insurance carriers from integrating herbal medicine into national health care plans is a perceived lack of scientific evidence; yet most of what is practiced in Western medicine, including the use of pharmaceuticals and medical procedures (e.g., cesarean sections, hysterectomies, mammography and PSA screening) are not evidenced-based, or are based on very poor evidence. In other words, as with the vaccines developed against COVID-19, the true level of safety and efficacy is only revealed through empirical observation, yet, when it comes to herbal medicine, the potential veracity of thousands of years of empirical knowledge and experience is completely discounted.
Some examples of modern research supporting historical indications
A number of examples of traditional herbal medicines illustrate their value based on modern research supporting historical indications, despite a lack of understanding of the pharmacological mechanisms associated with the activity. St. John’s wort (Hypericum perforatum) is one of the most ancient of herbal remedies in Western civilization and continues to be used today in much the same ways as in ancient times. Dioscorides wrote: a decoction of the fruit (taken as a drink with a pint of honey water) is available for sciatica. It expels much bilious excrement… Smeared on, it is good for burns (Osbaldeston and Wood 2000). Today, St. John’s wort is routinely used topically by modern medical herbalists for burns, scrapes, and neuralgic pain and internally for the treatment of depression, all traditional uses that are scientifically supported (Upton et al. 1997). While St. John’s wort was introduced into modern western medical practice by homeopaths, who regarded it as “arnica for the nerves”, a dictum attributed to Paracelsus (Jones 1880 Puente-Genil ) and arnica being a highly regarded healing agent for tissue damage, St. John’s wort became widely accepted by non-homeopaths. St. John’s wort has historically been one of the most relied upon botanicals for the treatment of wounds. Part of this activity is due to Hypericum’s antimicrobial activity, which modern research attributes to the essential oil, phloroglucinols, and flavonoids.
In a relatively modern study, a St. John’s wort oil, one of the oldest of Galenical St. John’s wort preparations, was shown to facilitate the healing of second and third degree burns (Saljic 1975) and successfully treat infection with Staphylococcus aureus (Negrash and Pochinok 1972) to a degree greater than standard treatment with sulfonilamide (Aizenman 1969). In another study of St. John’s wort, a tincture (1:10) of the herb was studied for its wound-healing properties and compared with Calendula, another widely used vulnerary. The effect of orally administered tincture of St. John’s wort was greater than topical application of Calendula tincture in the healing of incision, excision, and dead space wounds as evidenced by an increase in epithelization and wound-breaking strength (Rao et al. 1991). Another randomized, double blind, placebo-controlled clinical trial demonstrated efficacy for St. John’s wort to facilitate the healing of wounds in women who had undergone Cesarean section. Significant reductions were observed in scarring, pain, and pruritus (Samadi et al. 2010). In recognition of the ancient use of St. John’s wort as a healing balm, St. John’s wort oil was listed in the Pharmacopoeia Augustana (1612) and in the first Pharmacopoeia Londinensis (1618). Gerard (1633) wrote that St. John’s wort’s use as a balm for wounds, burns, ulcers and bites was without equal, stating; “for I dare undertake to cure any such Wound as absolutely in each respect, if not sooner and better, as any Man whatsoever shall or may with Natural Balsam”. Linnaeus (1749) in his Materia Medica reported on the use of the flowers and herb of St. John’s wort (Hypericum vulgare) to stop bleeding of the lungs and urinary tract and as a anthelmentic. In total, there are approximately 2000 years of empirical medical observation of the efficacy of St. John’s wort as a vulnerary (wound healing agent) and modern research to support this use.
Today, in much of Europe and the US, St. John’s wort is heavily marketed by phytopharmaceutical companies for depression and “improving mental health”. The Latin name Hypericum was derived from the earlier Greek eikon as recorded in the second century BCE by Nikander (Alexipharmaca V, line 603) and then later by the noted Greek physician Euryphon (upereikon; 5th century BCE) as yperikon, which meant “over an apparition”(Hobbs 1990; Robson 2003). Paracelsus also recommended St. John’s wort for “phantasmata”, which referred to psychoses and hallucinations, and for “healing of the soul”. In early times, depression was undoubtedly considered a form of possession, and from a humanistic perspective versus medical diagnostic perspective, depression can very much be described as a “disease of the soul”. In more modern times, formal clinical trials including meta-analyses, demonstrate St. John’s wort’s efficacy in the treatment of mild to moderate depression (Andreescu et al. 2008; Linde et al. 1996; 2008). In one of a few trials in which significant benefit was not demonstrated with either St. John’s wort or the approved anti-depressant imipramine, the herb performed better than the pharmaceutical both in patient outcome and side effect profile (Davidson 2002). Thus, even in a study where the herb presumably was not statistically significantly better than placebo, it never the less showed great efficacy than a formally approved pharmaceutical agent. More importantly, there are 1900 years of empirical experience of the use of St. John’s wort and more than 20 years of clinical data, including positive meta-analyses demonstrating efficacy for depression.
Ayurvedic medicine provides us with a particularly poignant example of a traditional herbal drug that has similarly stood the test of time and modern research—the three-fruit combination triphala. Triphala was first written about and used extensively more than 1000 years ago in the seminal text of Ayurveda the Caraka Samhita (~100 BCE). This formula is a mainstay of the practice of virtually every modern Ayurvedic practitioner today and, for many, it is the first therapy given before any others can be considered effective. Additionally, triphala is regarded as a rasayana, a rejuvenative tonifier used to preserve life (Ponnusankar et al. 2011). Much of the modern research of the individual herbs in triphala, as well as the combination itself, focuses on cytoprotective, immunomodulating, and antioxidant activity (Jagetia et al. 2004; Naik et al. 2005; Sairam et al. 2002; Srikumar et al. 2005), three pharmacological actions that can be considered to be associated with preserving life.
A last example is provided by a classic Chinese herbal formula known as si wu tang (four substance decoction). The formula was first written about in the Tai Ping Hui Min He Ji Ju Fang (Imperial Grace Formulary of the Tai Ping Era) between 1078–1085 CE. The formula was originally described for its use in menstruation, among other indications. Regarding menstrual difficulties, Western conventional medicine has few therapeutic options regarding gynecological health and fewer good therapeutic options. In 2003 in the US alone, there were approximately 602,457 hysterectomies performed, 538,722 (~89%) of which were for benign conditions (Wu et al. 2003). Some studies show that many hysterectomies are deemed unnecessary by second opinion or when alternative treatments are offered (BMJ 2014; Tan 2014). Some experts suggest that up to 90% of hysterectomies are not medically necessary (NWHN 2014 Randers ). Hysterectomy rates differ between countries, ranging from a high of 5.4 per 1000 women in the US (Farquahr and Steiner 2002); intermediate rates of 3.7 per 1000 in Italy (Materia et al. 2002); and a low of 1.2 per 1000 in Norway (Mepherson et al. 2002). The conditions for which hysterectomies, which are often accompanied by removal of the ovaries as prophylaxis against ovarian cancer (oophorectomy), are performed are predominantly to relieve symptoms of difficult menstruation that generally do not threaten lives. Current scientific evidence suggests that elective oophorectomy is not advisable for the majority of women as it may lead to a higher risk of death from cardiovascular disease and hip fracture and a higher incidence of dementia and Parkinson’s disease (Rocca et al. 2009). Recently, it has been concluded that preserving ovaries until at least the age of 65 years was associated with higher survival rates. Conversely, women who had a bilateral oophorectomy had a higher incidence of risk of all-cause death, fatal and nonfatal coronary heart disease, stroke, and lung cancer. Markedly, none of the groups in which oophorectomies were performed showed any correlation with increased survival (Parker et al. 2009) suggesting that alternatives, such as those offered with botanical medicines, such as si wu tang, offer a completely different therapeutic strategy with tremendous potential for reduction of harm and benefit. And, each of these examples offers clear evidence regarding the lack of evidence of some of the most common of medical procedures, despite Western’s medicine belief of adhering to principles of ‘evidence-based medicine’, even when these procedures cause irreparable harm or are ineffective.
While the botanical medicines discussed provide only a select view of the breadth of herbal medicines used worldwide and that have been supported by scientific study, the list can easily be multiplied by hundreds. More importantly, a review of the scientific literature reveals relatively few new discoveries regarding the uses of herbal medicine. Rather, studies mostly support the medical uses of the herbs that were known historically. For example, of all the plant-derived products currently available as prescription products, 72% are used in a manner, which parallels their ethnomedical use. Similarly, bioprospecting in the traditional herbal medical literature for potentially medicinal compounds has been demonstrated to yield more positive findings than random screening (Cordell and Colvard 2005; Tempesta and King 1994). Moreover, noted medicinal plant researcher Geoffrey Cordell (2002), underscores the need for humans to pay close attention to the preservation and investigation of traditional knowledge and natural resources that provide traditional and modern medicines for future generations, a message that should be taken to heart.
Therapeutics: Thinking beyond materia medica as a key to traditional healing modalities
Historically there were two primary arms to the study of traditional herbal healing modalities; therapeutics and materia medica. Therapeutics provides the theoretical framework by which health and disease is understood, the second the medicinal agents used, materia medica. Therapeutics provide the diagnostic principles that form the basis for which materia medica is to be applied. Today, the majority of herbal medicines are researched in a way that takes little or no consideration into the therapeutic framework in which herbal medicines should be used. Rather, individual herbs (relatively rarely, formulas) are investigated from a western pharmacological perspective for Western disease endpoints, completely removed from any cultural diagnostic context, such as of Ayurveda or TCM. The primary reason that Chinese medicine offers potentially effective treatments for functional gynecological problems, as discussed above, is due to the theoretical basis of understanding the physiology and pathology of the gynecological system. In Western medicine there is little understanding of the cause of functional gynecological imbalances. There are metrics with regards to identifying hormonal imbalances, growths, and abnormalities, but little to no understanding of the cause (see Goodman and Gilman). Conversely, Chinese medicine offers unique perspectives on promoting the health of the gynecological system through a myriad of theories of the causative factors of gynecological imbalances that correspond directly to therapies to address those imbalances. Whereas Western medicine offers hormonal replacement therapy (HRT) that itself increases mortality, along with palliative medications, surgery, and ablation therapies, TCM offers a host of therapies that include dietetics, baths, exercise, moxabustion, acupuncture, and a myriad of diverse herbal prescriptions, such as si wu tang, some of which have been in continued use for several hundred years. Many of these therapies have been demonstrated to have high rates of efficacy relative to controls for a wide range of gynecological imbalances including infertility, endometriosis, polycystic ovarian syndrome, dysmenorrhea, and pelvic inflammation, to name only a few (Jue and Fan 2009; Robinson and Wiczyk 2011, among others).
Defining traditional medicine and traditional medicines
Whether we consider evidence from cuneiform medical recipes from 3400 BCE, the birch fungus in the pouch of the Neolithic Oetzi the Iceman (circa 3300 BCE), or the writings of the 1st century physician-herbalist Dioscorides, whose writings remained the medical authority for more than 16 centuries, it is clear that medicinal plants have been the primary medicinal agents used throughout human history. The WHO has a long history of promoting the responsible use of herbal medicines worldwide. As a non-regulatory body, WHO is in a unique position to offer relatively unbiased guidance for how herbal medicines should be integrated into health care systems, both at the community and national levels, with the express purpose of what is in the best interest of the communities. This is a distinctly different position than national regulatory authorities, which have a myriad of social and economic biases that drive national health care policy. First and foremost, it is important to recognize that healing is a reflection of cultural belief whether that belief is based in indigenous traditions or modern paradigms. Therefore, the true integration of traditional healing practices, including the use of traditional herbal medicines, must be considered from the perspective of how traditional- and technologically-oriented healing systems differ, as discussed above.
Encompassed in traditional medicine are those practices that are based on indigenous theories, beliefs, and experiences that are passed from generation to generation. These traditions reflect well-established and nationally accepted systems of medicine such as Ayurveda and TCM, as well as more localized practices and philosophies of healing by minority communities such as Native American, South American, and indigenous aboriginal healers in Australia, to name only a few. In contrast, ‘modern’ or ‘conventional’ medicine is reflected in the concept of Western ‘allopathic’ medicine, a term ironically coined by the founder of homeopathy Samuel Hahnemann (1755–1843), and as generally applied to modern technologically oriented (Western) healing practices.
Traditional herbal medicines are more generally and specifically defined within WHO documents and are categorized into four main groups as follows (WHO 2004):
Saint-Jean-de-la-Ruelle Category 1: Indigenous herbal medicines: These medicines are used by local communities indigenous to a specific region and within a framework of cultural knowledge that may or may not be accessible to those outside of the community. WHO recommends that these medicines be allowed to be used freely by the communities. However, WHO stipulates, rightfully or wrongfully, that if these medicines enter the dominant market or go beyond the community boundaries, then those medicines must meet safety and efficacy requirements established in national regulation.
Category 2: Herbal medicines in systems: These medicines have a long history of use within a formalized system of medicine that are accepted by the country(s), for example, traditional Ayurveda, Chinese medicine, Unani-Tibb.
Category 3: Modified herbal medicines: These are medicines used in the above-mentioned categories but have been modified in some way that is no longer completely consistent with traditional systems. WHO contends these medicines should comply with national regulatory standards for safety and efficacy.
Category 4: Imported products with a herbal medicine base: These medicines represent imported raw materials or finished products that are registered for use in the country of origin. Again, WHO contends that these products have to meet the safety and efficacy requirements of the recipient country.
WHO more specifically defines herbal medicines as follows:
“For the purpose of these guidelines, the Consultation agreed that Herbal Medicines should be regarded as: Finished, labeled medicinal products that contain as active ingredients aerial or underground parts of plants, or other plant material, or combination thereof, whether in the crude state or as plant preparations. Plant material also includes juices, gums, fatty oils, essential oils, and any other substances of this nature. Herbal medicines may contain excipients in addition to the active ingredients. Medicines containing plant material combined with chemically-defined active substances, including isolated constituents of plants, are not considered to be herbal medicines.”
These categories clearly articulate the basis in which herbal medicines are to be allowed for use by indigenous communities, by practitioners of well-developed healing traditions, or integrated into the fabric of the national health care system. Moreover, the last definition of herbal medicine makes a clear differentiation between a traditionally prepared herbal medicine, a modern chemical isolate, and the combination of both. This is poignant as an herbal substance such as St. John’s wort has several centuries of accumulated data regarding indications, efficacy, and safety, and numerous modern studies documenting relative safety and efficacy, must be considered differently than the newly developed drug of the year that has no history of ever even existing let alone any data regarding safety and efficacy.
While some countries (e.g., Japan, India, People’s Republic of China) have worked diligently to represent traditional healing practices, including herbal medicine, as part of their national health care systems, as of 2005, approximately 60% of WHO member countries had no policy on traditional healing practices (WHO 2005). Moreover, while it is largely public interest that is driving the desire for greater access to herbal medicines, and thus driving policies, oftentimes, national policies are established with little or no input from the traditional medicine practitioner community. For example, neither the EU traditional medicines Directive 2001/83/ECnor the Dietary Supplement Health and Education Act (DSHEA), the latter that constitutes the primary access by which traditional herbal agents are allowed in the US, had formal input from the most well established of the traditional medicine practitioners, namely, Ayurvedic, Chinese medicine, or naturopathic practitioners. Thus, in both the US and the EU, it is industry with vested interests in specific herbal remedies that drive both health care policy and herbal medicine approval. This is a significant impediment to traditional healing practices as the availability of materia medica is often dependent upon the availability of crude herbs or herbal preparations through industry. The 2006 banning of the Chinese herb ephedra (Ephedra sinica) in the US is a clear example of how the misuse of an herb by industry, and subsequently by consumers, in stimulant and weight loss products led to significant adverse events. This resulted in both perceived and real concerns regarding the herb’s safety that resulted in a complete restriction from public and practitioner use, losing one of the most important articles of both Chinese and Western herbal materia medica, and losing access to an herb that, when properly used, had been used with a high degree of safety for more than 5000 years. Similarly, national policies regarding herbal medicines tend to focus predominantly on supply and manufacturing issues, with relatively little resources expended on human clinical trials, and fewer resources expended to investigate botanicals medicines in the manner in which they were traditionally used; as part of a multifaceted healing program that included dietary, stress, and behavioural modification. As begun by Paracelsus, too much emphasis is placed on studying herbal drugs in the same way that conventional drugs are studied, thus, often investigating the herbal drug out of the cultural and medical context in which it was historically used.
Pharmacognosy’s separation from traditional herbal medicine
“To talk about pharmacognosy is to follow the evolution of man’s knowledge during the various civilizations, i.e. the evolution of mankind from the dawn of time to the present.” DePasquale (1984)
Historically and until relatively recent times, pharmacognosy, the study of drugs derived from natural products, represented an intersect between traditional herbal medicine, ethnobotany (the traditional and cultural use of plant medicines and textiles), and scientific inquiry. In ancient times, the predecessors of modern pharmacognosists, represented by early medical scholars such as the Greek physician Dioscorides (1st century CE), were more closely linked with the practice of medicine than their descendents of the 20th century, many of whom were influenced by the chemical revolution taking place at the time and became more aligned with the business of drug development rather than the practice of medicine.
With its formal beginnings in the writings of the Austrian professor of medicine Johann Adam Schmidt (1759–1809), the original focus of pharmacognosy was on ensuring the identity, quality, and purity of plant-based drugs (Schmidt 1811). A principle focus at the time was on the source and quality of the raw material used in the manufacture of herbal drugs. This was prior to the advent of modern analytical chemistry and so the morphological and organoleptic characters of the crude plant drug, and later, the cellular structures of the plant as observed with a compound microscope, were the primary analytical tools used for quality evaluation. As analytical chemistry and the manufacture of synthetic drugs advanced, the science of pharmacognosy evolved into the field of pharmaceutical biology with an emphasis on natural products chemistry, molecular biology, and biotechnology. The modern pharmacognosist, rather than applying the skills of classical botanical pharmacognosy to ensure the identity, quality, purity, and integrity of plant drugs, which were being replaced by chemical drugs, were employed to search for novel compounds that could be exploited as drugs for commercial purposes. This change in scientific focus paralleled the changes in the medical profession described previously. According to a 1941 article in the magazine Science, “The desertion of the study of vegetable drugs soon became almost complete…at the present time researches dealing with plant medicinals are relatively rare and are becoming more so. Today is the heyday for organic synthetic chemicals.” (Griggs 1981).
The warp and woof of ancient and modern medical thought
Evolving medical theories similarly had significant impact on traditional healing modalities. The focus on the germ theory in Western medicine as a primary cause of pathology paralleled earlier medical philosophies of China’s Zhang Ji (Zhang Zhong Jing; ~150–210 CE) in his Shang Han Za Bing Lun (Shang Han Lun; Treatise on Cold Damage Disorders) that recognized pathogenic factors as a cause of epidemics. Germs and their destruction through the subsequent advent of antibiotics, an incredible life-saving but one-sided facet of disease treatment, became the primary focus of 20th century medicine that employed a militaristic strategy to search and destroy disease, a strategy that has persisted. This is in stark contrast to the vitalistic principles of Chinese and Ayurvedic medicine, whose primary focus was and is on the health of the host. The earliest text of TCM, the Neijing Suwen (475 BCE–221 CE) records; “Uneducated practitioners behave very aggressively, believing they can launch an attack. Before the old disease has ended, a new disease emerges in addition.” (Unschuld and Tessenow 2011). The myriad of serious negative side effects that are an inherent part of modern iatrogenesis provide ample evidence of the consequences of aggressive treatments.
According to traditional systems of healing, a healthy host, it is reasoned, is less susceptible to external pathogenic influences and has the greatest chance of health restoration, for example, from chronic degenerative diseases, for which modern medical constructs have little to offer. This realization was articulated in the historical TCM literature of Chinese herbalist and acupuncturist Li Dongyuan (1180–1252 CE). Li broke from the earlier traditions of the Shang Han Lun that focused on external pathogenic factors as the cause of disease and noted that if a person’s core health, as embodied in the health of the spleen and stomach (earth engendering school), is strong they will have resistance from external invasion no matter how strong the pathogen (Yang and Li 2002). This was a revolutionary concept in medical history that has yet to be practically applied in Western medicine. Most importantly, these two concepts, the Shang Han and Earth Engendering traditions, along with several other principle philosophies (e.g., yin-yang, four levels, seven emotions, and eight principles) reflect a system that embraces a myriad of medical philosophies that are applied according to the needs of an individual patient. This is in stark contrast to the single-minded focus of western medicine on a pathogen.
As modern pharmaceuticals increased in isolation, potency, and pharmacological exactness, herbal medicines largely vanished from use in Western countries. Conversely, Ayurvedic and traditional Chinese medicine remained relatively strong up until the 20th century. There were periods in the history of China and India (e.g., while under British rule) when traditional medical practices were formally discouraged in favor of European medicine. However, for example, after decades of influence of western medical theories in China, traditional Chinese medicine practitioners began to identify deficiencies in western theories and argued that traditional Chinese medicine had much to offer the totality of medical care and began a process of integrating Western and traditional Chinese medical theories (Chen 1999) that continues today. Subsequently, as of a 2005 survey conducted by the WHO, 1242 herbal medicines were listed on China’s essential drug list (WHO 2005). Similarly, after the end of British rule in India, Ayurveda once again regained its popularity and today, there are more hospitals of Ayurvedic care than there are conventional Western medical hospitals and the government actively supports the development of Ayurveda, as does the Chinese government for TCM. There are approximately 960 plants species used by the Indian herbal industry (Sahoo et al. 2010).
Herbal medicine in Europe experienced a resurgence for more practical reasons; after World War I, a number of drug patents, such as aspirin and heroin, were lost to the Allied Forces under the Treaty of Versailles (Jeffreys 2005). Similarly, during World War II, much of the infrastructure for drug development was destroyed in major cities throughout Europe. This forced many, most notably Germans, to once again look at traditional herbal medicines and began a trend of cultural use and research that has persisted to the present day.
While herbal medicine in the US survived in pockets of minority groups (African Americans and Caucasians from the rural south, certain Christian sects, Mormons, Native Americans, etc.), a true resurgence did not occur in the US until the 1960’s with the back to nature ‘hippy’ movements occurring then. This movement was overlaid with experimental use of a variety of hallucinogens, a number of which were of plant origin (e.g., Psilocybe, Datura, Lophora, Cannabis). At the same time, America was introduced to all the isms of the rest of the world such as Buddhism, Confucianism, Daoism, Hinduism, Shamanism. All of these philosophies emphasize an individual’s relationship within the context of the greater world as well as one’s responsibility to the world. This was in contrast to the dominant Christian constructs that suggest that “man has dominion over the earth”, a philosophy rejected my many as new thoughts from the east and from Native Americans were introduced. Regarding traditional medicine, these emerging philosophies partially established the foundation of nature being the primary healer and the recognition or belief that humans and plants have co-evolved and, because of that, plants were the optimal form of medicine for human health; a philosophy firmly held by many herbalists and natural health care practitioners today.