HerbalEGram: Volume 16, Issue 12, December 2019

By Connor Yearsley

In October 2019, the American Herbal Pharmacopoeia (AHP) released a monograph containing quality control standards and a therapeutic compendium (as one document) for boneset (Eupatorium perfoliatum, Asteraceae) aerial parts.¹

AHP claims that this is the first formal monograph on boneset, which may be one of the most effective anti-influenza plants in the North American materia medica. The monograph’s development involved original, in-depth analyses of boneset’s chemistry, which confirmed the presence of potentially toxic pyrrolizidine alkaloids (PAs) in the plant. This suggests the need for a more rigorous risk-benefit assessment or the creation of PA-free preparations of boneset.

AHP monographs establish identification, purity, and quality standards for botanical raw materials and preparations. The therapeutic compendia provide a comprehensive review of pharmacological and safety data, including medical indications and evidence from clinical, animal, and in vitro studies; modern and traditional uses; pharmacokinetics; pharmacodynamics; and guidance for structure and function claims. The compendia also cover dosages, interactions, side effects, contraindications, toxicology, and more. This information can be used by individuals in the herbal community, from consumers and health practitioners to industry members like quality control personnel, purchasing agents, and dietary supplement manufacturers.

The boneset monograph was a collaboration among AHP and researchers at Westfälische Wilhelms-Universität in Münster, Germany. Chemical analyses of boneset were performed by Steven Colegate, PhD, Dale Gardner, PhD, and Kip Panter, PhD, of the United States Department of Agriculture’s (USDA’s) Poisonous Plant Research Laboratory and Joseph Betz, PhD, of the National Institutes of Health’s (NIH’s) Office of Dietary Supplements. In all, 12 authors contributed to the monograph, and 18 experts in the fields of herbal medicine, botany, chemistry, pharmacognosy, pharmacology, and boneset cultivation reviewed it before publication. Work on the monograph began in 2014.

According to Roy Upton, RH (AHG), DipAyu, president of AHP and editor of the monograph, AHP began developing the monograph due to boneset’s reported high degree of efficacy during flu epidemics of the 1800s and early 1900s. “Boneset is one of few herbs whose efficacy was compared against conventional treatments at the time, and it was clearly saving lives when conventional therapies of the day were failing,” Upton wrote (email, November 14, 2019). “It was also one of the most widely used herbs by herbal physicians and practitioners of the time for flu. Considering that flu is always a public health issue, the need for effective medicines is apparent. We thought more people should know about boneset.”

Besides AHP’s cannabis (Cannabis spp., Cannabaceae) monograph, which was published in 2014, the boneset monograph was the most difficult to develop, according to Upton. In 2015, far into the monograph’s development, researchers at the University of Mississippi unrelatedly reported the presence of potentially toxic PAs in boneset.² Though common in other Eupatorium species, these compounds had never before been reported in boneset specifically, Upton explained. But, the researchers analyzed only one sample, including the root, even though the flowering tops were most often used traditionally.

At AHP’s request, PA analytical experts at the USDA analyzed the flowering tops of three boneset samples and found a wide range of PA variability among them. AHP then gathered, pressed, and identified more than 40 boneset specimens and sent them to USDA analysts, along with blinded controls (both positive and negative) that included herbs known to possess potentially toxic PAs (e.g., comfrey [Symphytum spp., Boraginaceae] and coltsfoot [Tussilago farfara, Asteraceae]), herbs that contain non-toxic PAs (e.g., echinacea [Echinacea spp., Asteraceae]), and herbs not known and unlikely to contain PAs (e.g., stinging nettle [Urtica dioica, Urticaceae]), among others. Some commercial boneset tinctures also were included, and the analysts were told how to make an infusion and decoction at dosages consistent with traditional use, since, historically, boneset was prepared mostly as tea.

To AHP’s dismay, all authenticated boneset samples and the teas and tinctures tested positive for the potentially hepatotoxic PAs lycopsamine and intermedine. Though the observed concentrations of these PAs in boneset were very low, according to Upton, they still exceeded interim rules established for herbal medicinal products (HMPs) in the European Union (EU).

The monograph was delayed for about two years while AHP gathered the samples, conducted the analyses, interpreted the data, and published the results.³ AHP also immediately reported its findings through its Herbal QRS Bulletin, and some companies removed boneset from their products, even though the risk of hepatotoxicity is likely low in general, according to Upton. Plus, boneset often is used only for short periods of time. Still, some populations, such as fetuses, infants, and people with already-compromised livers, are potentially sensitive to these PAs. Also, because PAs are cleared through hepatic glutathione systems, clearance may be less efficient or may not occur if these systems are compromised.

Upton noted that commercial honey is one of the greatest exposure risks for potentially toxic PAs⁴ and typically contains much higher PA concentrations than boneset does, but the EU has not established PA limits for commercial foods like honey. PAs in honey may be a potential contributor of hepatic disease of unknown origin. Other evidence suggests that, over multiple millennia, humans have adapted to deal with exposure to the less toxic PAs.⁵ In any case, formal toxicology studies are needed to determine if the PA concentrations in boneset, given at the dosages typically administered, are toxic. AHP could have conducted animal toxicology studies to help determine this, but it chose not to deviate from its longstanding no-animal testing policy.

Because of the PA issue, AHP “had to wrestle with whether” to publish the monograph, but after consulting with some of its primary advisors and longtime members, “all agreed that it was important to publish this,” Upton wrote. “We hope that regulators will use the information in the monograph as a way to set rational limits for boneset and other herbs that contain low levels of these compounds.”

In an AHP press release about the monograph, Upton was quoted as saying: “Because of the high degree of efficacy that [past] physicians reported regarding boneset, it is not an herb that should be lost from the materia medica. Perhaps it should no longer be used in common herbal bitters formulas, which are consumed more freely and frequently, but if I had a flu, I would not count out boneset.”

The boneset monograph is the 40th monograph published by AHP since 1998. It is available for purchase through AHP’s website¹ and was made possible by the financial support of EuroPharma USA, Nature’s Way, NOW Foods, Planetary Herbals, and Traditional Medicinals.

About Boneset

Native to eastern North America, boneset is a clump-forming perennial in the sunflower (Asteraceae) family. It prefers shady, moist areas and reaches four to six feet tall, with flat-topped clusters of small, fluffy, white flowers.^1,6 Boneset provides nectar for butterflies like the white-M hairstreak and bronze copper butterfly.⁷ The species name perfoliatum means “through the foliage,” because the plant’s hairy stem appears to perforate the bases of its wrinkled, opposite, lance-shaped leaves. All parts of the plant are bitter.^1,6

Accounts vary on the origin of the name boneset. In the 1800s, the plant was used for “breakbone fever” (a name that refers primarily to dengue fever) and “intermittent fevers” (a telltale symptom of malaria). Both dengue and malaria can cause joint and bone pain. Boneset sometimes was used as a quinine substitute. Native American tribes have used boneset as an antipyretic and cold remedy. They also have soaked broken bones in boneset tea. Native American use of boneset led to its introduction into American allopathic, Eclectic, and Thomsonian medical practices. The Eclectic physicians used boneset as a diaphoretic (to induce perspiration) and emetic. Modern naturopaths and herbalists still use boneset for flu, cough, and pain, as well as for its laxative and diaphoretic effects.¹

Image credits:

Boneset monograph cover courtesy of AHP.

Boneset photos ©2019 Steven Foster.

References

1. AHP Monographs — Boneset Aerial Parts. American Herbal Pharmacopoeia website. Available at: herbal-ahp.org/online-ordering-boneset-aerial-parts/. Accessed December 10, 2019.
2. Avula B, Sagi S, Wang YH, Zweigenbaum J, Wang M, Khan IA. Characterization and screening of pyrrolizidine alkaloids and N-oxides from botanicals and dietary supplements using UHPLC-high resolution mass spectrometry. Food Chem. 2015;178:136-48.
3. Colegate SM, Upton R, Gardner DR, Panter KE, Betz JM. Potentially toxic pyrrolizidine alkaloids in Eupatorium perfoliatum and three related species. Implications for herbal use as boneset. Phytochem Anal. 2018;29(6):613-26.
4. Scientific Opinion on Pyrrolizidine alkaloids in food and feed. EFSA Journal. 2011;9(11):2406.
5. Habs M, Binder K, Krauss S, et al. A Balanced Risk-Benefit Analysis to Determine Human Risks Associated with Pyrrolizidine Alkaloids (PA)—The Case of Tea and Herbal Infusions. Nutrients. 2017;9(7):717.
6. Eupatorium perfoliatum. Missouri Botanical Garden website. Available at: www.missouribotanicalgarden.org/PlantFinder/PlantFinderDetails.aspx?taxonid=277187&isprofile=1&basic=Eupatorium%20perfoliatum. Accessed December 10, 2019.
7. Common Boneset. EOL website. Available at: eol.org/pages/475561/articles. Accessed December 10, 2019.