Industry representatives, scientists and regulatory experts gathered in Brussels on July 14 as European regulators consider whether ashwagandha should undergo an Article 8 review—an EFSA process which could lead to restrictions, label requirements or a ban if safety concerns are identified.
The meeting, organized by Kerry Group and hosted by Member of the European Parliament Sean Kelly, marked the formal launch of Safeguard Ashwagandha, an initiative that seeks to ensure that the extensive body of peer-reviewed safety data informs regulatory decisions.
Speakers included Dr. Thomas Brendler, adjunct assistant professor of pharmaceutical sciences at the University of Illinois Chicago, and Dr. Mukesh Summan, global director of toxicology at Kerry Group, who reviewed clinical evidence supporting ashwagandha’s safety and benefits.
Having heard their evidence, MEP Kelly told delegates he believed any EFSA assessment of ashwagandha could be completed relatively quickly thanks to the strength of the data compiled by industry.
“I think there will be positives from this in due course,” he said, noting the ideal timing of the meeting. “If there is a vacuum of factual information then emotions can be whipped up through campaigns in the media and social media, and there could be a movement very quickly to ban ashwagandha. Having a discussion like this is vitally important.”
With the drive for regulatory harmonization in Europe, he highlighted that decisions should be made at the European level rather than through fragmented approaches across Member States, as has been the case thus far, with Denmark implementing a ban and several other countries now considering prohibition. As such, a Europe-wide opinion could set a precedent across the globe.
“If something is done at European level, it tends to become the global standard,” he said. “Europe has the highest standards in the world when it comes to safety and we need to guard that rigorously. With your evidence and clinical trials, you have plenty of examples of safety of the product.”
In his view, bans are often based on emotion rather than evidence, whereas the industry’s substantial body of research provides the foundation for EFSA to reach a rational and informed opinion through a robust assessment.
A review of that substantial body of evidence, presented by Dr. Brendler, covers 131 clinical trial reports and toxicological assessments. It determined that safety concerns raised by authorities were not supported by the available evidence.
“I think we are actually in a good spot as far as ashwagandha is concerned,” Dr. Brendler said during his presentation. “The data we have at our fingertips is sound and should be sufficient for regulators to come to an informed decision on consumer safety and benefits. Our job is to get this data to the regulators and, if we achieve that, I think we stand a good chance.”
Benefits of European assessment
Discussing the potential risks to industry should an Article 8 procedure be initiated, Monica Gispert Sararols, president of the Spanish Association of Food Supplements (Afepadi), warned that the opening of a review process alone could have significant consequences for the sector.
“These products have a long shelf life of around three years, so companies have to start trying to predict what is going to happen,” she said. “For companies, it extremely disruptive, so we have to be careful even with the initiation of these assessments because consumers start to question and companies start making decisions.”
Marianna Domolki, regulatory principal scientist at Kerry, highlighted that the introduction of bans in some Member States is already causing confusion for consumers.
“They don’t know why one member state would find it risky and another would not,” she noted. “As much as the industry might look at Article 8 as a risky tool because it could result in prohibition, in some respects it’s our chance to provide the information for EFSA to come up with what is a safe dose.”
In this scenario, if EFSA determines that ashwagandha is safe, any Member State with an existing ban may need to lift it.
Best outcome for consumer safety, evolving concerns with the science
Participants also expressed concern that banning ashwagandha could undermine consumer safety, potentially driving use of alternative ingredients that may be less controlled and supported by less robust evidence.
“I believe a ban on ashwagandha will not solve the problem because the consumer will move toward other adaptogens,” said Stefano Colicchia, director of regulatory and quality pharma & nutraceuticals, EMEA, at ingredient supplier Barentz. “If consumers aren’t able to find ashwagandha in brick and mortar stores, they will go online to find replacements, which will undermine trust and safety.
MEP Kelly agreed that prohibition could lead to the emergence of a black market and may ultimately pose greater risk to consumer safety than targeted measures such as dose limits or labeling requirements.
Also at issue is that thinking has not evolved with the evolving science since the German Federal Institute of Risk first raised safety concerns in 2013, with subsequent assessments simply echoing the same concerns.
“What baffled me was this laundry list of concerns never changed,” Dr. Brendler said. “It was carried all the way until the most recent recommendation for an Article 8 procedure.”
Meanwhile, the scientific evidence has grown substantially over the last decade, and regulators may not have adequately accounted for the latest available data.
Discussing his own review of individual toxicity case reports, Dr. Brendler said it was difficult to decipher causality in any case because the damage reported is “all over the place” with no clear signal of ashwagandha as the cause.
“What we are likely looking at is idiosyncratic cases that could occur with any ingredient, be it botanical or otherwise,” he said. “Additionally, co-morbidities and co-pharmacies are not being considered, which could put the culprit quite in a different place, not with ashwagandha as the cause.”
Criteria for quality
According to Dr. Summan of Kerry, the focus should be on ensuring quality across the market as “not all extracts are created equal”. To achieve this, clear criteria for what constitutes high quality ashwagandha extracts must first be established.
This criteria would include clinical and scientific evidence demonstrating efficacy and safety; robust quality control measures, including testing for heavy metals, contaminants and allergens; comprehensive chemical characterization to identify bioactive compounds, authenticate ingredients and ensure batch-to-batch consistency; and safety data derived from OECD-compliant studies, genotoxicity assessments and sub-chronic toxicity tests.
Kerry, for one, has conducted a safety study indicating safety of its Sensoril root and leaf extract at 19 times the standard daily dose and believes that studies of this type can help ensure product quality and consumer safety.
“At Kerry, we are supportive of an Article 8 review as we believe that EFSA will conduct a science-led evidence based review based on the body of data and ignore misinformation,” Dr. Summan said.
Protecting ashwagandha and its benefits, establishing safety profile
Blake Ebersole, co-founding member of the Ashwagandha Standards Alliance, a newly-formed US-based coalition also seeking to protect ashwagandha, joined the meeting virtually and highlighted questions about whether plant part—root, leaf or stem—could be the source of safety concerns.
“While it’s true that some ashwagandha products are mislabeled as to plant part in order to reach a number on the label, regulations already require accurate plant part and potency labels,” he said. “What we are dealing with is not a question of safety but a question of quality, standards and proper labeling.”
As such, he added, the Ashwagandha Standards Alliance is dedicated to lobbying governments to ensure they do not “confuse the need for consistent standards with alarmist irrational responses which conflict with evidence and approvals in other nations.”
Dr. Brendler further noted that regulators want to see evidence establishing safe dosing and duration of use for the herb. This requires identifying a common basis across the different preparations available on the market, which has been aided by industry’s willingness to share information about the composition of their extracts.
“This is important information to elucidate what the consumer is ingesting and with that data at hand from the majority of the industry we could derive that dosing recommendations pretty much aligned with what the Ayurvedic Pharmacopoeia establishes,” he said.
His review concluded that this remained the case even after applying a commonly used 100-fold safety factor (FDA, 2007).
Finn Murray, owner of Health stores Ireland, questioned why there has been little discussion or focus on the risk-benefit cost ratio and the human health costs associated with banning ashwagandha.
“There’s a missing piece in advocating for the clear benefits of this herb,” he said. “EFSA has started to look at risk-benefit analyses…so this notion of assessing risk without looking at the positive human health element—reduction of disease and reduce public health costs—I’d like to see that part of the discussion opened up.”
Delegates agreed, and Dr. Brendler noted that his review outlined 12 scientifically-supported benefits of ashwagandha, with sleep-related benefits supported by the strongest body of evidence.
