In 2020, the Technical University of Denmark (DTU) Food Institute carried out a risk assessment of ashwagandha for the Danish Veterinary and Food Administration (DVFA or Fødevarestyrelsen in Danish).
Building on a previous negative assessment in 2008, DTU noted some studies that had shown harmful effects to thyroid and sexual function as a result of eating unspecified extracts of the root and extracts of other parts of the plant. It concluded it could not establish a safe lower limit for intake for the root or extract of the root and, as a result, ashwagandha was banned in Denmark.
Some ashwagandha industry stakeholders have criticised the DTU report for failing to objectively evaluate the safety of this botanical and, with regulatory experts warning that ashwagandha is under growing scrutiny in the EU, they are now starting to speak out.
Failing to distinguish between roots and leaves
According to Tom Johnsson, co-founder and head of R&D at Swedish nutraceutical company MedicineGarden which supplies ashwagandha, the "key problem" with the Danish report was that the DTU Food Institute failed to differentiate between the leaves and the root – something that he says should be fundamental in a risk evaluation.
In the Ayurvedic tradition, the leaves or stem of the ashwagandha plant, which contain higher concentrations of withaferin A, withanone, and alkaloids compared to the root, are used topically to treat skin conditions. They are rarely used internally and only for very specific indications such as birth control or to treat certain cancers.
Johnsson said: “... when [DTU] tried to find out the ratio between different active ingredients in different parts of the plant they looked on small studies from different parts of India, Bangladesh and other countries and found very heterogenic results which made them conclude, ‘we cannot distinguish between the root, leaves, stem and berries.’
“The strange thing is that when you look carefully in the risk assessment - DTU have made a distinction. For instance, they estimate the content of withaferin A in root to 0.032% but in leaf to be 0.9-1%. That is a 30-time difference which should have given them a clear indication that the leaf and root have different properties.
“If DTU had made a conclusion saying that the aerial part of ashwagandha or unspecified root extract can have a risk at very high dosage, then they would have been correct,” Johnsson told Vitafoods Insights.
“But what they have done is take the conclusions for stems, leaves and berries and [conclude] that the root can harm thyroid or sexual hormones. That is absolutely wrong and contradicted by many new studies both in humans and in animal.
Johnsson added: “But what is as scary, is that other regulatory experts have uncritically believed the report without carefully examining the references and conclusions. Now, when the so-called safety risk with ashwagandha is described, it sounds like many regulatory [agencies] have come to the same conclusion – but that is wrong, everything springs from the same Danish report.”
Report failings? 'Cherry-picked' studies
The co-founder of Medicine Garden felt DTU Food Institute had “cherry-picked” which studies to include in its 2020 risk assessment to substantiate the negative conclusion it had already come to in 2008.
DTU also failed to fully report the conclusion of some studies included in the assessment, Johnsson said.
For instance, DTU referred to eight studies, (four animal studies and four human studies,) that evaluated the effect of ashwagandha root on sex hormones, seven of which showed normalised levels of sex hormones – “normalising” or “balancing” the body’s hormones is one of ashwagandha’s functional attributes – while one animal study from 2002 showed a reduced willingness to mate.
However, DTU did not report in its assessment that the authors of the 2002 animal study themselves concluded that this reduced willingness to mate was “not due to changes in testosterone levels or toxicity but may be attributed to [...] the sedative activities of the extract” (among other possible causes such as GABAergic or serotonergic activities).
Johnsson also questioned why DTU chose to only reference two studies conducted on the branded ashwagandha ingredient KSM-66 when, at the time, there were 10 published double blind studies available, including clinical studies, demonstrating its safety and effect.
World Ashwagandha Council report
Johnsson’s concerns over the robustness of the DTU assessment are shared by, the wider ashwagandha industry.
This year, the World Ashwagandha Council and Ixoreal Biomed, supplier of KSM-66 ashwagandha, produced a 74-page evaluation of the 2020 DTU Food Institute’s assessment.
Signed by Dr Girish Tillu, executive director of the World Ashwagandha Council; Dr JB Gupta, its secretary; and Dr Deepak Langade, professor and head of pharmacology at the D. Y. Patil School of Medicine, the report urged DTU to conduct a new safety evaluation on root extracts only.
“[This is] an important aspect since studies on other parts of the plants will most certainly lead to different conclusions on safety, which may be incorrect and seriously misleading.”
The World Ashwagandha Council report also noted that a large number of well-done studies have since been published regarding both efficacy and safety since 2020.
“This circumstance, together with the fact that DTU has ignored the evidence that there are significant differences between the root and other plant parts both in terms of both effect and safety, indicates that there are good reasons to redo the report.
“We understand that the spirit of the DTU report is to ensure the safety of people, and we agree with DTU that there can be safety concerns when aerial parts of ashwagandha are used internally and that it is important that root extracts should be well-defined and free from withaferin A, withanone, and alkaloids,” they wrote.
Extraction methods should also be taken into account
European registered toxicologist Matti Viluksela is professor emeritus at University of Eastern Finland and principal scientist and founder of Finnish consultancy Toxistence. He was commissioned by KSM-66 to produce an expert opinion on the implications of the Danish assessment for the supplier.
Viluksela also noted that DTU Food Institute had failed to differentiate between the composition of leaf and root extracts and between various methods and solvents used for extraction, which can result in different compositions. Water extraction is the traditional method while other methods are “more efficient” he noted. Methanol- and ethanol-extracted ashwagandha have slightly different profiles, for instance.
Viluksela concluded that the safety concerns raised by DTU Food Institute were not relevant for the ashwagandha extract KSM-66, because its composition is substantially different from those extracts included in DTU’s assessment and because sufficient safety studies, both nonclinical and clinical, existed indicating its safety.
Medicine Garden’s Tom Johnsson admitted that the landscape in 2008 for safety regulators was very different to today and there was little information on ashwagandha in Europe when DTU made its first assessment.
However, this was not the case in 2020, he said, and the authority could have “very easily” found information regarding the importance of distinguishing between the aerial plant and the roots. By 2020, for instance, the World Health Organization had published a monograph on the plant, and it also featured in the British Pharmacopoeia and United States Pharmacopeia.
Medicine Garden has tried to approach the DVFA many times, but it has refused to engage with the company because Medicine Garden does not have a commercial entity registered in Denmark. Vitafoods Insights also contacted the DVFA and DTU for comment but did not receive a response.
Malmö-headquartered MedicineGarden, whose portfolio includes other branded nutraceutical ingredients such as triGUT lactic acid complex and curaMIN (BCM95), plans to start doing business in Denmark, which will require the DVFA to look at the safety evaluations.
In its home country of Sweden, Johnsson said the company has had “good dialogue” with the health authorities there. In September 2022, the Swedish Food Agency announced that the Danish risk assessment could also be applied in Sweden but that each municipality would decide on individual cases.
“They have seen that there is so much substance in the safety evaluation that we have been presenting, they have decided not to ask us for more information. They haven't given us a direct approval that it's safe, but they have been very clear in the communication that they see the differences between different extracts.”
MedicineGarden: ‘A well-defined, standardised root extract is safe’
As for next steps and a possible resolution, MedicineGarden is looking to the recently formed World Ashwagandha Council, established by India’s Ministry of AYUSH (ayurveda, yoga, naturopathy, Unani, siddha and homeopathy), to enter into dialogue with Danish authorities and challenge its position.
It is also considering filing a legal complaint with the Swedish health authorities although Johnsson said he hoped the issue would be resolved between the Danish authorities and the World Ashwagandha Council before.
“Our goal with the discussion with DTU and Swedish health authorities is that they come to the logical conclusion: as long as you have a well-defined root extract that is standardised, it is safe [whether] it's ethanol, methanol, or water-extracted,” Johnsson said.
“Water is better in our opinion because it resembles the root 100% [...] but as long as you use a standardised root extract, with the natural relations between actives [...] it's still ok.”
In 2021, the Ministry of AYUSH issued official guidance that advised against using ashwagandha leaves in Ayurvedic formulations.
However, ashwagandha products that blend root extracts and leaves (which are much cheaper than the root) do exist on the market – and, as such, could continue to cause problems for ashwagandha suppliers of root extract who try to distance themselves from such products.
Asked if he thought EU regulatory authorities may, in the future, ban ashwagandha leaves and rule that only root extract can be sold, as is currently the case in Poland, Johnsson said this may be the case.
Such a scenario would benefit root extract suppliers and could remove the possibility of consumer confusion regarding the safety of different parts of the plant.
Another scenario, Johnsson added, could be that authorities approve root-leaf blended extracts on a case-by-case basis but only if the manufacturer can provide the safety data to demonstrate it has removed the problematic actives from the leaves.