Chemistry conundrum: U.S. experts weigh in on European ashwagandha concerns

A growing number of European Member States have banned or are considering a ban on ashwagandha-containing products​ due to alleged potential negative impacts on human hormones put forth in a highly criticized risk assessment report from the Technical University of Denmark (DTU).

The recent editorial, written by ​the heads of the National Center for Natural Products Research (NCNPR) at the University of Mississippi—a U.S. Food and Drug Administration (FDA) center of excellence for botanical research—expressed concern about the information used to inform the controversial determinations. 

“In an ideal world, regulatory decisions are based on technically sound, critically reviewed and reproducible scientific data,” they wrote. “This is not always the case in actuality; indeed, it might not always be possible with botanical research.”

Dearth of verification of raw materials

The editorial highlighted several issues with scientific data referenced in the DTU report on ashwagandha’s quality and safety attributes—notably the dearth of information on verification of the botanical raw materials used in studies, preparation of the test materials and utilization of plant parts other than ashwagandha roots.

It explained that the characteristic phytochemicals, or ‘quality markers’ vary significantly depending on whether they are extracted from the roots or other plant parts (i.e., leaves, twigs and stems), making standardization of the extraction process the essential primary step prior to conducting preclinical and clinical studies.

“In the absence of such critical information, it is impossible to accurately reproduce the safety and efficacy attributes of ashwagandha or any other botanical material,” they wrote. “Concurrently, we acknowledge that the academic research system encourages the rapid publication of scientific results for various reasons. Unfortunately, this calls into question the scientific robustness of some of the published research on ashwagandha… Consequently, this may negatively influence or skew decision-making by regulators.”

The editorial also examined the issues with the references that triggered DTU’s concerns about ashwagandha’s impact on thyroid function, spermatogenesis, liver toxicity, herb-drug interactions and other biological effects, including its purported effect as an abortifacient agent.

"We did not see solid evidence to come up with a decision that would ban ashwagandha," Ikhlas Khan, PhD, director at NCNPR, shared in an article published on the University of Mississippi website. "There is not much scientific evidence to prove that it is a dangerous thing."

Amar Chittiboyina, PhD, assistant director at NCNPR, added: "Some might say, 'Well, who are you to judge?' The NCNPR has a strong track record of in-depth scientific expertise, lending credibility to [its] work in botanical dietary supplement research."

No documented provenance

Drs. Khan and Chittiboyina noted that as with many dietary supplements, consumption of excessively large doses of ashwagandha may pose significant adverse effects but that a scientific report explicitly identifying ashwagandha for induction of abortions has yet to be made. 

They added that the statement by the World Health Organization that the 'root has been used as an abortifacient' has no documented provenance, but that despite this, it has been reported in the technical literature without independent citation.

“This precautionary statement is suspected to have been derived from a part of the Ayurvedic medical system," they wrote. “Contrary to this statement, some published data suggest that ashwagandha is safe during pregnancy and can boost the health of women pre-and post-birth (Dongre et al., 2015). Simultaneously, one should also consider the long history of ashwagandha (Ayurvedic multi-herb tonic formulation Chyawanprash) usage by a multimillion population for centuries prior to the implementation of regulations based on questionable scientific data.”

The editorial also highlighted that most of the purported adverse effects of ashwagandha observed in animal models directly contradict the long history of usage in Ayurvedic medicine.

“Although some of the scientific findings are suggestive of safety concerns of ashwagandha, a lack of quality controls and characterization, the use of extracts from wrong plant parts, testing at concentrations significantly exceeding the traditional levels, and differential species or part-specific biological effects all combine to call into question concerns related to male fertility, sex hormones and reproduction,” Drs. Khan and Chittiboyina concluded.

As next step, they suggested that experts or expert committees conduct a review of available literature to identify questionable or non-relevant studies and provide enhanced scientific guidance to regulators.

Ashwagandha drives herbals market in the U.S.

At this year's Oxford International Conference on the Science of Botanicals (ICSB)​, an annual conference organized by NCNPR, Bill Giebler, director of content and insights at the Nutrition Business Journal​, presented the latest data on supplement sales.

He said that the herbs and botanicals segment is both strong in terms of growth and dollar sales, historically “doing the same thing that the industry is doing but doing it a little bit better” and currently expanding at 4.4%. 

Ashwagandha appeared as a top driver of growth, alongside echinacea, elderberry, ginger, aloe, gingko biloba, maca, fenugreek, horny goat weed and ginseng.

Source:  ​Journal of Ethnopharmacology​
doi: 10.1016/j.jep.2024.117871​
“Current issues in phytomedicine research - Conundrum on the chemistry of ashwagandha and its biological effects”
Authors: Amar Chittiboyina and Ikhlas Khan