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Building the next era of the natural health industry on solid, evidence-based foundations is an exciting prospect. For naturally sourced medicines to be fully integrated into mainstream health care, it must be recognized that evidence for variable, chemically complex natural medicines is product specific. This is particularly true for botanical-based formulations and so-called phytomedicines. Barriers to identifying “specific evidence” products† and the consequences of these barriers are examined. A pathway to link published clinical evidence to products on the market today is presented, and products that have been independently assessed through this pathway are named. Further changes are underway that will provide increased transparency, support informed choice, and underpin a sustainable future for the natural health industry.
On a cold morning in June 1999 at an herbal medicine conference in Lismore, Australia, Professor Varro E. Tyler, PhD (1926–2001), painted a picture of a science-based future for the natural medicine sector. Built on views he expressed in Rational Phytotherapy: A Physicians’ Guide to Herbal Medicine, 3rd ed. (Springer, 1998),1†† which he wrote with German scientists Volker Schulz, MD, and Rudolf Hänsel, PhD, Tyler spoke about scientific evidence for specific herbal medicine products in various popular health categories (e.g., digestion, cough/cold, sleep, etc.).
After Tyler’s talk, Mark Blumenthal, the founder and executive director of the American Botanical Council (ABC), described how the future offered the potential for integration of evidence-based herbal medicine products into mainstream clinical practice. (Blumenthal is the editor of the fifth edition of the book, now called Rational Phytotherapy: A Reference Guide for Physicians and Pharmacists[Springer, 2004], which is still in print.2)
The conference, called “Herbal Medicine into the New Millennium,” coincided with the announcement of a new natural medicine research and commercial hub called “Cellulose Valley” — an initiative to build a technology park at Southern Cross University in New South Wales to support the medicinal plant and natural health industry. The plan for Cellulose Valley ultimately was not successful, but what about the vision of Tyler and Blumenthal?
The natural health industry is at an important inflection point. The size and level of acceptance of the natural health movement suggest that the next phase may be full integration into mainstream health care. Many barriers to long-term progress need to be overcome. Building a future that is based on transparency around supply chains, product quality, and reproducibility is needed. Informed product choice based on specific scientific and clinical evidence can also help maintain and enhance the sector’s growth and benefits for public health.
Evidence Is Product Specific
An evidence-based vision for the natural health sector
Tyler described Rational Phytotherapy as “the first qualitatively complete, science-based herbal resource in English.”1 Written primarily for physicians and other health care professionals, the book provided a guide to product choices and was indicative of new mainstream acceptance of specific evidence on natural health products. Tyler stated his belief that Rational Phytotherapy “will have a considerable impact on the therapeutic use of botanicals in the English-speaking world.”1
Since the book was first published, many members of the natural medicine community have recognized that evidence for natural health products should be product specific. ABC, for example, links herbal medicine studies to the specific product(s) used, including manufacturer names and product details (e.g., extract standardization, concentration, etc.) when possible. However, the vision for a global, specific evidence-based botanical dietary supplement industry has not yet materialized.
Addressing chemical variability of finished products
Finished herbal products from different manufacturers are not interchangeable due to variability in the ingredients’ chemical composition. Accordingly, clinical trial evidence should be considered product specific.
For example, the chemical variability of products among batches and brands of ginkgo (Ginkgo biloba, Ginkgoacae) leaf extract has been shown using nuclear magnetic resonance (NMR) spectroscopic data. A study published in 2021 found that products containing EGb 761®* — the world’s most clinically tested ginkgo extract, according to the manufacturer (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) — had high batch-to-batch consistency. However, several apparently similar products from other manufacturers, despite complying with specifications listed in regional pharmacopeias, were shown to be highly variable.3
Commercial formulations of turmeric (Curcuma longa, Zingiberaceae), another commonly used herbal ingredient, have also been shown to vary substantially, both among different products and within product batches. A 2019 review of 11 different turmeric formulations showed a high degree of variability in curcumin bioavailability. Researchers reported that three products exhibited bioavailability that was more than 100 times higher than reference (pure, unformulated) curcumin.4
The variability of products and batches, even of registered phytomedicines in Germany, a highly regulated market, may be very high. According to one study published in 2001,‡ five batches of eight different St. John’s wort (Hypericum perforatum, Hypericaceae) products that were purchased in Germany varied considerably in concentrations of two constituents: hypericin and hyperforin. Notably, the study found large differences in hyperforin content even among batches of the same brand. However, one product, Remotiv® (also known as Ze117**; Max Zeller Söhne AG; Romanshorn, Switzerland), which is manufactured to contain negligible amounts of hyperforin, had consistent levels of this compound.5 The levels and variability of hyperforin found in the other brands is concerning, as the constituent is known to interact with conventional pharmaceutical drugs.6,7
Functional or clinical benefits of finished products are not consistent
Product variability also impacts the biological effects of natural medicines.
In a study of three different finished products made from ginkgo leaf extract in 12 male volunteers, only one, Ginkgold®* (Nature’s Way; Green Bay, Wisconsin; made from EGb 761), showed superiority to placebo and a dose response. This is despite the fact that the labels of all three products state that they are standardized to 24% ginkgo flavone glycosides.8 Further evidence of the potential impacts of ginkgo product variability was shown in a 2018 animal study, which found differing functional effects of six different “ginkgo extract” products on neuronal networks in mice.9
Successful clinical trial results sometimes are not reproduced, potentially due to changes in the product, among many other reasons. Two studies by a researcher who used the same supplier — but apparently different specifications — of a finished product containing kava* (Piper methysticum, Piperaceae) in participants diagnosed with generalized anxiety disorder had different results. In the first trial, significantly more participants were classified as remitted compared to placebo, but the second trial demonstrated no significant differences. In the second trial, the kava product* had a non-significantly lower number of participants classified as remitted compared to placebo. This might be explained due to significant differences in the intervention used in these two studies, as the participant populations were similar.10,11 On the other hand, studies assessing anxiety tend to have a lower reproducibility in the treatment outcome due to the inherent complexity of the condition, according to an expert reviewer of this article. Introducing product variability further complicates the interpretation of such studies.
The need for recognition that evidence is product specific in the natural medicine sector extends to probiotics. In a 2018 review of 228 trials of probiotic products, the authors concluded:
Strong evidence was found supporting the hypothesis that the efficacy of probiotics is both strain-specific and disease-specific. Clinical guidelines and meta-analyses need to recognize the importance of reporting outcomes by both specific strain(s) of probiotics and the type of disease. The clinical relevance of these findings indicates that health-care providers need to take these two factors into consideration when recommending the appropriate probiotic for their patient.12
Herbal CONSORT guidelines and Cochrane Collaboration acknowledge evidence of product specificity
Meta-analyses and systematic reviews are considered to provide the highest level of evidence, particularly for chemically well-defined medicines, such as single-chemical entities with equivalent bioavailability. However, in the natural medicine field, pooling the results of different products in a review and drawing conclusions is potentially problematic and often listed as one of the study limitations by the authors.
High variability among products and within batches can lead to unreliable conclusions in systematic reviews and meta-analyses. Pooling high-quality botanical products with low-quality ones may make positive findings less likely. Even a positive systematic review may be of limited value for a specific evidence-based natural health sector since the inclusion of variable formulations of a specific substance can lead to the mistaken impression that all products containing that substance can deliver the documented clinical benefits. Therefore, a positive review may lead to the purchase and use of unrelated products based on this misperception of their apparent similarity. It also may incentivize other manufacturers to enter the herbal supplement market with a different formulation of the same botanical that makes the same health-related claims as the clinically tested product without proper substantiation.
In 2003, 17 international experts began a process to improve the reporting of herbal medicine interventions in randomized, controlled clinical studies. They recognized that variation in herbal medicines is high, and therefore evidence is product specific. They also noted that very few published trials include the information necessary to identify the specific intervention used. To address this lack of transparency, the authors published the CONSORT (Consolidated Standards of Reporting Trials) extension for herbal interventions in 2016, which provides guidelines for reporting randomized, controlled trials of botanical medicines.13 Their thorough checklist of the precise details of the intervention used is still considered state of the art for the sector. They also noted that variation in herbal products used in different trials “precludes” pooling data in systematic reviews and meta-analyses since “invalid inferences may result from the combined data.”13
Recognizing this challenge, two sizable Cochrane Reviews published in 2008 and 2014, respectively, have pointed out that evidence is product specific:
St. John’s wort products available on the market vary to a great extent. The results of this review apply only to the preparations tested in the studies included.14
Echinacea preparations available on the market differ greatly as different types (species) and parts (herb, root or both) of the plant are used, different manufacturing methods (drying, alcoholic extraction or pressing out the juice from fresh plants) are used and sometimes also other herbs are added.15
Specific evidence requirements in regulatory guidelines
The acknowledgment of evidence being product specific is directly or indirectly referenced by regulators and the World Health Organization (WHO).
The European Medicines Agency (EMA) states:
Because herbal substances/preparations are complex mixtures of constituents, e.g., herbal extracts produced by different manufacturers are never identical, the following aspects must be considered: Assessment of comparability must include details of composition, available data on the specification of the preparation and information on the manufacturing process. The specification and manufacturing process is particularly important in those cases where bibliographic data on highly purified extracts are presented or where a new method of preparation of an extract is used.16
Even the Therapeutic Goods Administration (TGA) in Australia, which does not assess the specific clinical evidence for products and does not require that products have premarketing approval or follow WHO guidelines on Good Agricultural and Collection Practices (GACPs), states: “The evidence must relate to the whole medicine [i.e., the finished product], the same active constituent(s) with a similar dosage regimen, dose form and route of administration to the medicine for which a claim is being made.”17
Unfortunately, outside of certain markets where regulators assess these aspects, there is no transparency or an independent review process for global herbal medicinal products to ensure that finished products have specific clinical evidence and health benefits that are consistently reproducible.
Barriers to Progress
Naming complexity for medicinal plants
For medicinal plants, using correct names is a huge challenge in scientific research and the interpretation of that research. The names of raw herbal materials are not consistent in published scientific literature, and this creates confusion and a lack of transparency about the specific evidence.
The American Herbal Products Association (AHPA), a natural products industry organization, published a list of medicinal plants used in the United States in the first and second editions of Herbs of Commerce (1992 and 2000).18,19 It sought to standardize the use of vernacular (common) names for these plants for the US industry. Nevertheless, there have been many taxonomic advances and name changes in recent decades, and standardizing how names are used in different contexts, by different peoples and cultures, is a daunting task. (AHPA is planning to release the updated third edition of Herbs of Commerce in 2023.)
Extensively studied medicinal plants have on average 14 synonyms, with some species’ common names exhibiting high complexity. For example, the name “ginseng” is associated with 170 common or pharmacopeial names and 58 scientific names, according to the Royal Botanic Gardens, Kew, in the United Kingdom.20 This means that, unless standardized, authors and editors of scientific papers might use different names to describe the “same substance.” Not only is this a barrier to transparency about the efficacy of specific products used, but it also can lead to a high degree of confusion in adverse reaction reporting, as the identity of the substance in the implicated botanical product may not be clear. Kew has worked for many years with the WHO, the US Food and Drug Administration (FDA), and others to improve the understanding of the many synonyms for medicinal plants around the world.
Misidentification and adulteration of ingredients
According to the nonprofit conservation organization TRAFFIC, between 60% and 90% of medicinal and aromatic plants (MAPs) in commerce are wild collected.21 This means that, despite the many experienced and skilled wild collectors, identification of original plant materials is susceptible to human error. This represents a potentially significant risk in supply chains and value networks of medicinal plants. Depending on the quality of training and experience throughout the value networks, including the application of appropriate identity testing at certain (and, in some cases, required) stages of the supply chain, accidental misidentification of plant materials may occur. Unknowingly, herbal ingredients may not be the species ordered by manufacturers. Another challenge is that medicinal plants usually have specific times in their growing stages when they have optimized levels of biologically active constituents. Properly qualified and trained collectors can help ensure that plants are harvested at the optimal time and the correct plant parts are used.
Accidental misidentification of medicinal plants is not the only problem. There are financial incentives for unethical players in the supply chain to substitute easier-to-collect or lower-cost plant materials and therefore intentionally adulterate the products. The ABC-American Herbal Pharmacopoeia (AHP)-National Center for Natural Products Research (NCNPR) Botanical Adulterants Prevention Program (BAPP) has been leading a campaign to assist in the prevention of accidental or deliberate adulteration of MAPs by reporting on types of adulteration in the marketplace and assessing the fitness for purpose and viability of analytical methods for authenticating botanical ingredients. Since 2011, BAPP has investigated adulteration issues related to more than 25 different popular botanical ingredients.22 It also has created a self-regulatory tool (a standard operating procedure, or SOP) to assist botanical industry companies in removing adulterated ingredients — if the level of adulteration renders the material an “irreparably defective article” — from global botanical supply chains.23
Disruption in global supply chains caused by the COVID-19 pandemic and other instabilities in international trade, including an uncontrolled inflationary cycle at the time of this writing, are expected to exacerbate these problems.
Regulatory heterogeneity and regulatory change
Natural health products are regulated differently from market to market.24 The same product could be considered a dietary supplement, a traditional or complementary medicine, a medical device, or a prescription or non-prescription medicine depending on the regulatory requirements of the specific national market, the intended use of the product, and other factors. This complex, heterogeneous regulatory environment presents a significant cost to the industry. It also creates little common ground for harmonization and standard setting. A lack of mutual recognition of regulatory approaches among countries means that a uniform global standard for reproducibility of products and scientific evidence to support claims is currently not in place. More than this, it reinforces “thinking in silos,” which is a barrier to change for all stakeholders.
At a global level, introduction of regulatory change to provide a solution to identifying products with specific evidence seems a distant hope. Market access already has been granted to hundreds of thousands of products, and enforcing requirements for specific evidence to support claims on these products would likely be highly disruptive. Many regulatory authorities have a risk-based approach, and mechanisms for the exchange of pharmacovigilance information are better established than those for efficacy and benefit claims. With safety as the primary aspect of concern for regulators, it may be that removal of a product from the market due to lack of specific evidence of reproducibility and clinical effectiveness has the potential to result in the loss of relatively safe and potentially beneficial products. Such regulatory action might punish some members of the industry for not investing in scientific research, which has been disincentivized by the regulatory environment by permitting the borrowing of evidence for claims.
Regulators operate in an environment of many competing stakeholders and under extreme political and media scrutiny. Any regulatory changes often require lengthy and expensive consultation processes. Since 1999, the global botanical industry has expanded dramatically, and scientific evidence for medicinal plant ingredients and finished products has exploded. Regulatory change typically lags behind scientific developments, particularly due to lack of international harmonization or mutual recognition. It seems unlikely that a global regulatory change to help consumers find natural health products with specific evidence will take place anytime soon.
Lack of transparency in reporting specific evidence in
scientific and popular media
Unfortunately, the level of precision about herbal interventions described in the CONSORT herbal extension is rarely if ever reported in published clinical trials. In a recent literature search, none of the thousands of PubMed records of randomized controlled trials (RCTs), which included some well-researched herbal medicines, included all the information listed in the CONSORT guidelines.25 In fact, most trials did not name the product used at all. This means that even if one has the time and knowledge to search the scientific literature, it is still not possible, without contacting the authors, to identify the specific product used.
Popular media also rarely identify the specific commercial brand of clinically tested products when describing clinical studies. If a successful trial is reported, it may not be clear to readers that the results are product specific. In a well-meant but counterproductive attempt to appear independent, researchers, journalists, and editors actively seek to avoid identifying the specific product used. This situation can cause consumers to seek any product containing the perceived “same substance,” which results in the use of unrelated products and a financial benefit to those companies. If this were the case for wine, another complex and naturally sourced product, then publicizing the winner of a wine award could cause an increase of sales of everything containing grapes. In this author’s opinion, it is a dysfunctional market where clinical research-based innovators fund the claims of their competitors, and consumers are unknowingly misled about the benefits of the product they are taking.
Race to the Bottom — Commoditization
Evidence for the lack of science underpinning the market can be seen with the growing commoditization of the sector, as widely available products are commonly considered interchangeable with each other. The scale of this commoditization can be understood when studying the extensive Therapeutic Research Center (TRC) Healthcare’s Natural Medicines database.26 This database contains evidence-based information on more than 250,000 dietary supplements, natural medicines, and integrative therapies. Natural Medicines captures the information on labels of commercial products available in the United States and is a content provider for the Dietary Supplement Label Database (DSLD) of the US National Institutes of Health (NIH). In June 2022, the Natural Medicines database had records of 7,260 products containing DHA (an omega-3 fatty acid), 5,514 products containing ginkgo, and 4,550 products containing glucosamine in the US market.
In such a crowded environment where scientific evidence is difficult or impossible to link to a specific product, a price war can result, with corresponding increased pressure on manufacturers to purchase and sell ingredients of lower quality. Lower-priced products, often with broader distribution, commonly replace premium evidence-based products, potentially delivering less reliable health benefits. This occurred, for example, in Australia with the herb bacopa (Bacopa monnieri, Plantaginaceae). Initial success of the bacopa-containing product KeenMind™,* based on randomized controlled studies, dropped as it was substituted by commodity competitors. A few years later, the combined market for bacopa-containing products was a fraction of the size, presumably because consumers were not satisfied with the products’ effects. It took 10 more years for the herb, and KeenMind, to regain the sales lost.
If further evidence is needed that the herbal medicine sector in this generation is not built entirely on science, we can see this in HerbalGram’s 2021 Herb Market Report of the top-selling herbal dietary supplements in the United States.27 Extensively studied herbs such as ginkgo, St. John’s wort, black cohosh (Actaea racemosa, Ranunculaceae), bacopa, valerian (Valeriana officinalis, Caprifoliaceae),and Asian ginseng (Panax ginseng, Araliaceae), for example, were not among the 10 top-selling herbs of 2021. This suggests that either the commercially successful products of today are built on weak scientific ground with respect to their clinically documented benefits, or there is a failure to communicate their public health potential. Neither scenario is healthy for the sector.
In a struggle to differentiate and expand product marketing claims, and due to the lack of recognition that evidence is product specific, companies have been encouraged to incorporate multiple ingredients to make claims. These combinations, despite their potential efficacy, dramatically increase the complexity of the products and might introduce negative interactions or synergies among ingredients. Additionally, as there are cost constraints and a limit to the number or size of tablets, capsules, etc., that consumers and patients are willing to take in a day, there is pressure to reduce the daily dose of individual ingredients to subtherapeutic levels. Unless the benefits of specific finished products are documented adequately in published clinical trials, and/or unless they contain adequate levels of clinically tested ingredients in a therapeutically equivalent form, these combination products may deliver less consistent results.
Finding Specific Products Used in Published Clinical Trials
Building on Rational Phytotherapy,2 The Handbook of Clinically Tested Herbal Remedies, edited by Marilyn Barrett, PhD, was published in 2004 (Haworth Herbal Press).28 The purpose of this extensive two-volume book is to “provide consumers and health care professionals with a means to distinguish those herbal products that have the backing of clinical evidence to substantiate claims of efficacy.” This seminal work helped establish the principle of connecting products on the shelf to the scientific evidence that supports them. Since then, clinical research has increased substantially but also a need to further understand the quality, specifications, and reproducibility of the products.
More recently, a research project to identify the products used in clinical trials was launched in August 2020. The Natural Health Science Foundation (NHSF; doing business as Empowered By Evidence, a nonprofit organization described in the next section) is performing this work in collaboration with Monash University in Melbourne, Australia. The EBE-led project used the CONSORT herbal extension checklist to capture the identity of herbal interventions in clinical trials. Since then, the project has reviewed published clinical trials on PubMed on products containing 14 herbal medicinal substances, and the most recent assessment reviewed 1,000 clinical trials of omega-3-containing products.25 Although many thousands of clinical trials have been published, very few identify the actual commercial product used, and none fully describe the herbal intervention according to best practices of the CONSORT extension.13 (Details of the product data captured in the project can be found in the footnote below.‡‡)
Therefore, finding the names of specific products used in clinical trials is not easy and beyond the reach of consumers and busy health care professionals. Even if they are provided in a published study, the research often was conducted years ago, and it is not guaranteed that products of the same name that are available today are equivalent to the product used in the clinical trials.
EBE and Product Accreditation
Independence and transparency
In 2014, a group of international researchers, stakeholders, and companies that have invested in clinical research formed the NHSF to encourage more clinical research and the recognition of “specific evidence” products and to promote their use in natural self-care and health care. Doing business as EBE, this organization began work to educate the industry and the marketplace that evidence is product specific. This has involved the launch of course materials explaining how variability in natural health products is controlled and why it is important to control it.
Given the lack of transparency about which products have specific evidence of efficacy and reproducibility, EBE developed an independent, transparent, and robust process to inform choice based on product-level scientific evidence. In June 2018, at the international conference Phytopharm, held near Zurich, Switzerland, Professor Theo Dingermann, PhD, of Goethe University Frankfurt, announced a draft process to the industry and research sector. After an open public consultation, potential improvements in the process were discussed with industry members and researchers at the Society for Medicinal Plant and Natural Product Research (GA) annual meeting in Innsbruck, Austria, in September 2019. In 2020 and 2021, pilot assessments were performed, and a governance and review team was established.29
The EBE accreditation process was formally opened in mid-December 2021 and closed for applications at the end of January 2022. A total of 14 applications from phytomedicinal product manufacturers around the world were received.30 This product accreditation is directed toward empowering consumers and health care professionals to make informed choices about products based on specific evidence.
Quality and equivalence assessment
Applicants are required to identify at least one clinical trial on their product. Most applicants, including all of those whose products were approved, provided more than one clinical trial. To provide a link between current batches of the product to the clinically studied batches, applicants had to show that they have sufficient control of the source material (i.e., the plant) to ensure a highly consistent product. These quality and equivalence specifications, standards, and processes are independently reviewed by qualified assessors. For herbal medicines, assessments are required at three levels: the raw plant material, extract (or active ingredient), and finished product. Applicants are required to follow GACPs or pass an equivalent independent assessment. Importantly, this requires proper botanical identification of the raw plant material (addressing adulteration concerns) and consideration of the sustainability and conservation of these important and sometimes threatened plants.
The quality of the submitted studies is independently assessed to determine the benefits the specific product has demonstrated. While specific claims are a matter for the regulations in the market in which the product is marketed, the efficacy review examines the scientific evidence in the published studies.
Most products submitted for consideration failed the initial assessment. Unsuccessful applicants were provided detailed reviews of the shortcomings in their submission and advice on how to correct these gaps. The most common reason for failure to meet the EBE standard was failure to demonstrate equivalence of the batch currently on the market to the clinically tested batch. Details of each application are strictly confidential.
These products are available under different names and from different suppliers in more than 30 countries worldwide. The assessment includes equivalence of all these brands to the clinically studied batches of these products. Full details of their brand names and distributors around the world are available on EBE’s website (www.EmpoweredByEvidence.org/ebe-database/).
Informed Choice and the Future
Improving naming consistency
The scientific team at the Royal Botanic Gardens, Kew, is addressing the most fundamental starting point, the naming of medicinal plants. Kew has developed the world’s first comprehensive index of common and scientific names of medicinal plants. Its online tool helps users identify the correct scientific names of medicinal plants. This free service, called the Medicinal Plant Names Services (MPNS, current version 12), covers 34,000 plants, is updated annually, and is available on Kew’s website.31
After a successful grant in 2021 from the Wellcome Trust, MPNS will be expanded further over the next few years. This initiative, called “Plants for Health,” seeks to further assist in accurately naming plants and to promote a common language around this crucial foundation of the science of herbal medicine.
Improving access to evidence
TRC Healthcare’s Natural Medicines database represents a substantial opportunity for the future of informed choice of products based on specific evidence. EBE-accredited products will be flagged in the Natural Medicines database, so that users can find products that are made reproducibly and have specific clinical trial evidence to support them.
Natural Medicines is the largest science-backed natural medicines and supplements database in the world. It has more than 1,400 natural medicine monographs with evidence-based content about safety and effectiveness. Its independent editorial team is supported by the oversight of hundreds of frontline and specialty clinicians, pharmacists, and nurses. The comprehensive evidence-based monographs are fully referenced, and the products used in the clinical trials are identified. Natural Medicines increasingly is looking to assist informed choice of specific evidence natural health products, which will have profound implications for informed choice.
Natural Medicines provides content for many leading health authorities, including the NIH and FDA in the United States and the United Kingdom’s National Health Service. It is a content provider for the DSLD database, Medline/PubMed, numerous hospital pharmacies, and other databases.
Empowered by Evidence — Next steps
EBE is processing more applications for accreditation. In addition to this, applicants whose products do not yet meet the standard are given guidance on how to improve the evidence for their products. It is encouraging that many of these improvements are related to product documentation and can be realized in a short time without substantial cost.
Information about EBE-accredited products and the process is available on EBE’s website. EBE plans to release additional educational content, including resources to support the industry in developing reproducible and additional clinically tested products.
Unfortunately, Blumenthal and Tyler’s vision of the impact of Rational Phytotherapy, which they described at the 1999 herbal medicine conference, has not been fully realized. Many scientific and clinical publications on botanical ingredients, finished dietary supplements, and phytomedicinal products do not recognize that evidence is product specific. This continues to undermine the scientific basis for informed natural health product selection and removes incentives for research. Moreover, the public health benefits of natural health products are less assured when scientific evidence does not guide product choice.
Many people believe in the sustainability and growth of the natural health sector, particularly phytomedicines, which a rigorous scientific and clinical foundation will help deliver. Anyone who wants to see a specific evidence-based future for the phytomedicine and dietary supplement industry is invited to join the movement to be “Empowered by Evidence!”
Nigel Pollard is chair of the board of directors of Empowered By Evidence, a New York-based nonprofit with a vision to bring specific evidence-based natural health products into mainstream health care. He also chairs several other organizations and has more than 22 years of chief executive experience. Pollard has a background in pharmaceuticals and 23 years of experience in the natural medicines industry, with a strong belief in the highest standards.
Pollard is the chair of the board of directors of several health care-related companies or consultancies, including Metavate Consulting, Key Pharmaceuticals, and Vine Digital. He is also an advisory board member of Altum International, a medicinal cannabis company. Pollard is the founder and former CEO of the natural products company Soho Flordis International.
† As the name suggests, a “specific evidence” product has scientific research (e.g., clinical trial evidence) on the finished natural health product. The product batch used in clinical research must also be equivalent to current batches.
†† Rational phytotherapy “employs various levels of empirical and scientific evidence with sound reasoning to determine the most appropriate ways to apply the benefits of herbs and phytomedicinal products to human health.”1
* This product has not been independently assessed by the nonprofit Empowered By Evidence (EBE; see “EBE and Product Accreditation” section for more information).
‡ Although the study is more than 20 years old, it can be inferred that registered phytomedicines that have maintained marketing authorizations in Germany are equivalent to past batches. This is because for this level of regulatory approval, any subsequent changes in the supply chain, manufacturing process, or composition of these products must be reported to the regulator. Hence, it is likely that the manufacturing process has not changed since the study, and variability may still be an issue in these products.
** This product has been independently assessed by EBE.
* This product has not been independently assessed by EBE.
‡‡ The data captured by the Monash University/NHSF team, derived from the CONSORT extension for herbal interventions, include: citation; first author; journal/book; publication year; create date; PMCID; NIHMS ID; doi link; eligibility status; reason for exclusion; strain or extract; brand name/extract code; name of company that owns the product; name of other potentially active ingredients in the product; website of company that owns the product (if available); country of clinical study; regulatory status in country of study; evidence of stability; method of authentication of raw material; qualitative testing; description of special testing/purity testing; finished dosage form/posology; finished product, standardization; and claim area studied.
- Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer Publishing; 1998.
- Schulz V, Hänsel R, Blumenthal M, Tyler VE, Telger TC (translator). Rational Phytotherapy: A Reference Guide for Physicians and Pharmacists. 5th ed. Berlin, Germany: Springer Publishing; 2004.
- Kulić Ž, Butterer A, Germer S. Comparing multiple batches of finished Ginkgo biloba products from international markets including EGb 761® by principal component analysis based on NMR spectroscopic data. Planta Med. 2021;87(15):PC4-4. Available at: www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0041-1736843. Accessed February 6, 2023.
- Jamwal R. Corrigendum to “Bioavailable curcumin formulations: A review of pharmacokinetic studies in healthy volunteers” [J. Integr. Med. 16(6) (2018) 367–374]. J Integr Med. 2019;17(4):310. doi: 10.1016/j.joim.2019.05.002. Available at: www.sciencedirect.com/science/article/pii/S2095496419300573?via%3Dihub. Accessed February 6, 2023.
- Wurglics M, Westerhoff K, Kaunzinger A, et al. Comparison of German St. John’s wort products according to hyperforin and total hypericin content. Journal of the American Pharmaceutical Association. 2001;41(4):560-566. doi: 10.1016/S1086-5802(16)31280-3. Available at: www.sciencedirect.com/science/article/abs/pii/S1086580216312803?via%3Dihub. Accessed February 6, 2023.
- Nicolussi S, Drewe J, Butterweck V, Meyer zu Schwabedissen HE. Clinical relevance of St. John’s wort drug interactions revisited. British Journal of Pharmacology. 2020;177(6):1212-1226. doi: 10.1111/bph.14936. Available at: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.14936. Accessed February 6, 2023.
- Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ. Understanding drug interactions with St John’s wort (Hypericum perforatum L.): Impact of hyperforin content. Journal of Pharmacy and Pharmacology. 2018;71(1):129-138. doi: 10.1111/jphp.12858. Available at: https://pubmed.ncbi.nlm.nih.gov/29411879/. Accessed February 6, 2023.
- Itil TM, Martorano D. Natural substances in psychiatry (Ginkgo biloba in dementia). Psychopharmacology Bulletin. 1995;31(1):147-158. Available at: https://pubmed.ncbi.nlm.nih.gov/7675979/. Accessed February 6, 2023.
- Bader BM, Jügelt K, Schultz L, Schroeder OH-U. Ginkgo biloba L. (Ginkgoaceae) leaf extract medications from different providers exhibit differential functional effects on mouse frontal cortex neuronal networks. Front Pharmacol. 2018;9. doi: 10.3389/fphar.2018.00848. Available at: www.frontiersin.org/articles/10.3389/fphar.2018.00848/full. Accessed February 6, 2023.
- Sarris J, Stough C, Bousman CA, et al. Kava in the treatment of generalized anxiety disorder: A double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013;33(5):643-648. doi: 10.1097/JCP.0b013e318291be67. Available at: https://pubmed.ncbi.nlm.nih.gov/23635869/. Accessed February 6, 2023.
- Sarris J, Byrne GJ, Bousman CA, et al. Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study. Aust NZ J Psychiatry. 2020;54(3):288-297. doi: 10.1177/0004867419891246. Available at: https://pubmed.ncbi.nlm.nih.gov/31813230/. Accessed February 6, 2023.
- McFarland LV, Evans CT, Goldstein EJC. Strain-specificity and disease-specificity of probiotic efficacy: A systematic review and meta-analysis. Front Med (Lausanne). 2018;5:124. doi: 10.3389/fmed.2018.00124. Available at: https://pubmed.ncbi.nlm.nih.gov/29868585/. Accessed February 6, 2023.
- Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. Reporting randomized, controlled trials of herbal interventions: An elaborated CONSORT statement. Ann Intern Med. 2006;144(5):364-367. doi: 10.7326/0003-4819-144-5-200603070-00013. Available at: https://pubmed.ncbi.nlm.nih.gov/16520478/. Accessed February 6, 2023.
- Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008;4:CD000448. doi: 10.1002/14651858.CD000448.pub3. Available at: https://pubmed.ncbi.nlm.nih.gov/18843608/. Accessed February 6, 2023.
- Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2014;2:CD000530. doi: 10.1002/14651858.CD000530.pub3. Available at: https://pubmed.ncbi.nlm.nih.gov/24554461/. Accessed February 6, 2023.
- Committee on Herbal Medicinal Products. Guideline on the assessment of clinical safety and efficacy in the preparation of EU herbal monographs for well-established and traditional herbal medicinal products. European Medicines Agency website. September 19, 2017. Available at: www.ema.europa.eu/en/documents/scientific-guideline/guideline-assessment-clinical-safety-efficacy-preparation-eu-herbal-monographs-well-established_en.pdf. Accessed February 6, 2023.
- Therapeutic Goods Administration. Listed medicines evidence guidelines: How to demonstrate the efficacy of listed medicines is acceptable. Version 4. Therapeutic Goods Administration website. June 2022. Available at www.tga.gov.au/sites/default/files/evidence-guidelines.pdf. Accessed February 6, 2023.
- Foster S, ed. Herbs of Commerce. Silver Spring, MD: American Herbal Products Association; 1992.
- McGuffin M, Kartesz J, Leung A, Tucker A. Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
- Medicinal Plant Names Services. Royal Botanic Gardens, Kew website. Available at: www.kew.org/science/our-science/science-services/medicinal-plant-names-services. Accessed February 6, 2023.
- Jenkins M, Timoshyna A, Cornthwaite M. Wild at Home: Exploring the Global Harvest, Trade and Use of Wild Plant Ingredients. Cambridge, UK: TRAFFIC International; 2018. Available at: www.traffic.org/site/assets/files/7339/wild-at-home.pdf. Accessed February 6, 2023.
- Blumenthal M, Gafner S, Foster S, Cardellina JH, Khan I, Upton R. Preventing adulteration and fraud in botanical ingredients in the international marketplace: The ABC-AHP-NCNPR Botanical Adulterants Prevention Program. Planta Med. 2019;85(18):1400. doi: 10.1055/s-0039-3399662. Available at: www.thieme-connect.com/products/ejournals/html/10.1055/s-0039-3399662. Accessed February 6, 2023.
- Adulterants Prevention Program releases Best Practices SOP on Disposal/Destruction of ‘Irreparably Defective Articles’ [press release]. Austin, TX: American Botanical Council; October 19, 2022. Available at: www.herbalgram.org/news/press-releases/2022/best-practices-sop-for-the-disposaldestruction-of-irreparably-defective-articles/. Accessed February 6, 2023.
- Thakkar S, Anklam E, Xu A, et al. Regulatory landscape of dietary supplements and herbal medicines from a global perspective. Regul Toxicol Pharmacol. 2020;114:104647. doi: 10.1016/j.yrtph.2020.104647. Available at: https://pubmed.ncbi.nlm.nih.gov/32305367/. Accessed February 6, 2023.
- Data on file. Empowered by Evidence website. Available at: www.empoweredbyevidence.org. Accessed February 16, 2023.
- Natural Medicine [database]. Therapeutic Research Center website. Available at: https://naturalmedicines.therapeuticresearch.com. Accessed February 27, 2023.
- Smith T, Resetar H, Morton C. US sales of herbal supplements increase by 9.7% in 2021. HerbalGram. 2022;136:42-69. Available at: www.herbalgram.org/resources/herbalgram/issues/136/table-of-contents/hg136-feat-hmr/. Accessed February 8, 2023.
- Barrett M. The Handbook of Clinically Tested Herbal Remedies. Vol. 1 and 2. Abingdon, UK: Haworth Herbal Press; 2015.
- Product accreditation. Natural Health Science Foundation website. Available at: https://nathealthscience.org/accreditation/. Accessed February 6, 2023.
- Pre-assessment for EBE product accreditation. Natural Health Science Foundation website. Available at: https://portal.nathealthscience.org/PreAssessment. Accessed February 6, 2023.
- Medicinal Plant Names Services [database]. Royal Botanic Gardens, Kew website. Available at: https://www.kew.org/science/our-science/science-services/medicinal-plant-names-services. Accessed February 27, 2023.