This safety assessment is made in the light of the questionable conclusions of a Danish risk assessment of ashwagandha (May 2020 (DTU DOCX. no. 19/1030299). A risk assessment that uncritically also forms the basis for the HoA report June 2024 and a Dutch risk assessment RIVM2024-0029.
The following statement shows that the Danish risk assessment for ashwagandha is not applicable to KSM66.
Background: The Danish Food Safety Authority, together with DTU (Technical University of Denmark), has published a "Risk Assessment of Ashwagandha". The report concludes that ashwagandha root can negatively affect sex and thyroid hormone.
This conclusion is mainly based on the fact that DTU uncritically assumed that root, leaf and stem contain the same active substances and that results from studies on leaf and stem can therefore be applied to root.
DTU's failure to understand the difference between different plant parts is confirmed in the introduction to the report where they write
"DTU has included experimental studies that have been performed with plant parts other than the root, as they have common ingredients. Withanolides and alkaloids are also found in other plant parts and experimental studies with plant parts other than the root can therefore help to shed light on possible effects of the root. "
The conclusions of the report are particularly noteworthy because DTU has not been able to demonstrate any negative effects of ashwagandha root on either sex or thyroid hormone. Of the 8 studies on root (4 animals and 4 humans) referred to by DTU regarding the effect on sex hormone, seven show increased/normalized values, while one animal study shows reduced willingness to mate after a dose 300 times higher than the normal dose. The unwillingness to mate is, according to the author of the article, probably caused by the sedative effect of the high dose - not due to negative effects of sex hormone(Ilayperuma2002).
What DTU has shown instead, by referring to studies on leaves, stem and berries or the whole plant, is that these plant parts, in high doses, can have a negative impact on both sex hormones and on the liver. A known fact because above-ground parts contain high levels of withaferin A and withanone. Substances that are very potent (cytotoxic), and have a completely different side effect profile compared to roots.
https://doi.org/10.1016/j.jaim.2018.12.008
https://pubmed.ncbi.nlm.nih.gov/34345852
For the above reasons, it is always the root that has been used internally. One of the most common uses of Ashwagandharot is increased sexual desire and function. As a result, Ashwagandharot increases the body's resistance to stress, which indirectly contributes to the normalization of sex hormone levels. Topical parts of Ashwagandha have never been used in these areas - as they have partly the opposite effect - which DTU disregarded.
To clarify that only root should be used in food supplements/tea, the Indian Ministry of Health has published an official report advising against the use of plant parts other than root (2021).
https://ayush.gov.in/resources/pdf/quality_standards/advisory-on-aswagandha.pdf
Dr. Senia Johanson PhD Pharmacognosy, Uppsala University comments on DTU's choice of methodology as follows (Safety evaluation on the root part vs.the entire plant/ aerial parts, March 2023):
"To determine the safety and efficacy of a herbal dietary supplement, it is important to conduct the safety assessment on the specific part of the plant used, in this case the root, which DTU disregarded. This is essential because the content of several substances, such as alkaloids, withanone and withaferin A, vary considerably between the root, leaf, stem and berries of ashwagandha."
Medfiles, a specialist in regulatory affairs, clinical trials and drug safety https://medfilesgroup.com/sammanställde published a report "Clarification on the differences in content of Withania somnifera (ashwagandha) roots and leaves" inMarch 2025. This report has been submitted to the European Commission.
The conclusion of the report, which is based on an analysis by Alkemist Labs, Inc USA (Dec 2024), is summarized as follows:https://www.alkemist.com/
"Both HPTLC and HPLC techniques were used to analyze the differences in composition between root and leaf in the same plant. The report shows that the amount of withaferin A (cytotoxic) and withanolide A (primary bioactive withanolide) differs significantly between leaf and root.
Figure 2 shows that the content of withaferin A is much higher in leaves while withanolide A has a significantly higher concentration in root. In addition, a large difference in the amount of total flavonol glycosides was observed between the two plant parts.
Green Chemistry: KSM66 is the only ashwagandha extracted using "Green Chemistry", an environmentally friendly method that took 14 years to develop. The method is based on a 3000-year-old tradition using only milk and water. The raw material consists exclusively of organic Ashwagandha root from our own certified farms. Ixoreal, the company behind KSM66, thus has 100% control from seed to finished extract.
The milk and water technique allows both water-soluble and fat-soluble substances to be extracted. The result is a full spectrum extract containing the same active substances, in the same natural ratio as in the dried whole root. KSM66 is thus an exact replica of the preparation form used traditionally for more than 3000 years.
Withanone and Withaferin are not present in KSM66: KSM66 is the only commercially available ashwagandha root extract standardized on 6 withanolides. Each batch is checked for purity and active substances. The levels of Withanone (liver retardant) and withaferin A (cytotoxic) are below measurable values.
2.5 billion daily doses/year: KSM66 is the most widely used ashwagandha extract in the world and is found in over 4000 different products outside India. The annual use of KSM66 outside India is approximately 2.5 billion daily doses. No serious side effects have been reported.
1 million packs in Sweden: KSM66 was launched in Sweden in the fall of 2017 and has since been Sweden's best-selling herbal dietary supplement. The success is equally evident in Finland, where KSM66 was launched in 2018, and in Norway, where KSM66 was launched in 2019. In these three countries, around 400,000 packs are sold annually, corresponding to around 24 million daily doses per year. No serious side effects have been noted.
- 25 published clinical studies, one approved for publication. All studies are in healthy, stressed men and women aged 15-75 years. 25 of these are double-blind, placebo-controlled and randomized.
- 13 clinical studies under review in healthy, stressed men and women aged 15-75 years (11 under peer review, 2 internal review).12 of the studies are double-blind, placebo-controlled and randomized
29 of the clinical studies have been published/completed after DTU made its report.
- 15 preclinical/toxicology studies have been conducted of which 10 are published, 2 accepted for publication and 3 under review. The majority of the studies were performed at a dose equivalent to 200 times the normal dose (2000 mg/kg body weight). Acute toxicity, mutagenicity, long-term effects and reproduction have been studied.
All are published after DTU made its report
- In addition, 20 double-blind, placebo-controlled studies are ongoing.
- 12-month safety study: The study was conducted under the direction of a US CRO and is published in Phytotherapy Research. The study included participants from the US, Italy and India.
https://onlinelibrary.wiley.com/doi/10.1002/ptr.70096
Study summary: 191 people received 600 mg KSM66/day for 12 months. A large number of liver, kidney and thyroid values were monitored during the study. No clinically significant differences between baseline and endpoint were noted. However, both cortisol and testosterone levels normalized. 7 out of 10 experienced a clinically significant improvement in quality of life, among other things.
- Global safety study: The study included 1000 men and women aged 15-65 years. The study was conducted under the direction of a US CRO and included people from five continents. The study is under review and published as a preprint.
https://doi.org/10.6084/m9.figshare.27302223.v1
The authors of the study conclude that KSM66/Ashwagandha root extract is well tolerated and safe for adults to use (over 15 years). The adverse event rate in the KSM66 group was 5.6% versus 9.2% in the placebo group. All side effects were mild and transient.
- High-dose safety study with 2000mg/day: 86 subjects, men and women aged 18-65. Dose 2000 mg KSM66 per day (just over 6 capsules) for 12 weeks. No clinically relevant effects on renal, hepatic, hematologic and thyroid functions were noted. The study is under review and published as preprint.
https://doi.org/10.6084/m9.figshare.27330000.v2
The frequency of adverse events: In total, nearly 4000 people were included in the studies. In the KSM66 group, 3.81% of adverse events were recorded and in the placebo group 4.77%. All side effects were mild and transient.
Sex hormone: 13 studies have evaluated the effect on sex hormone in men and women. All studies show normalized/improved values of sex hormone, sperm motility, etc. All values are within the normal range after intake of KSM66.
8 of the studies have been published, one accepted for publication, 3 under per review and one under internal review.
11 of the studies are published/completed after the DTU report.
Liver function: 13 studies have evaluated liver function.
All studies show that KSM66 does not adversely affect any liver values. 8 of the studies are published, 7 under per review and one under internal review.
All are published/completed after the DTU report.
Thyroid: 5 studies have evaluated the effect on the thyroid. 2 in subclinical hypothyroidism and 3 in normal thyroid. KSM66 does not affect a healthy thyroid but has a mild normalizing effect in subclinical hypothyroidism - a result of normalized cortisol levels. 3 of the studies are published, 2 are under review.
4 of the studies were done after the DTU report.
1. 90-day toxicology study in 100 Wistar Albino rats (2023)
KSM66 was given at doses up to 2000 mg/kg body weight (200 times the normal dose) per day for 90 days (one tenth of the rat's life expectancy).
Results: No changes were observed in the test animals in relation to the control group in terms of body weight, hematology or biochemical parameters. There were also no changes compared to control in thyroid hormones or liver values.
The study is published in Toxicology Reports.
https://www.sciencedirect.com/science/article/pii/S2214750023000963?via%3Dihub
2. Reproduction study on 92 Wistar Albino rats (2025)
40 male rats were divided into 4 groups and fed with 0, 500, 1000, 2000mg KSM66/kg body weight per day. Dosing started 24 days before mating and continued throughout mating.
52 female rats were divided into equivalent groups and given identical doses of KSM66 for 63 days starting before mating and throughout gestation and lactation.
Results: No abnormal clinical signs of toxicity were observed in either the adult rats or their offspring during the study.No significant changes were observed in body weight, food consumption, oestrus, mating behavior, weight, anogenital distance, hormone levels, organ weight, or histopathology in the treatment groups compared to the control group. No statistically significant changes were observed in the TSH and T4 levels of the males, females or their offspring compared to the control group.
The study is published in Frontiers of Pharmacology.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1572025/full
1. Expert opinion on "Expert Opinion on the Safety Evaluation Studies with Ashwagandha (Withania somnifera) Root Extract KSM-66 as a Food Supplement" by Professor Matti Johannes Viluksela, Ph.D., DABT, ERT. Nov 2024
2. Safety assessment "Summary of safety data on KSM-66® Ashwagandha including comments on DTU National Food Institute's risk assessment report of ashwagandha/Withania somnifera" by Pia Karjalainen, M.Sc., Senior Regulatory Affairs Expert, and Mari Lyyra, M.Sc.,Head of Operations, Medfiles Ltd. DEC 2024
3. Ashwagandha safety with special focus on liver. Professor Emeritus Dr. Åke Nilsson Lund University. May2024
Professor MattiJohannes Viluksela, Ph.D conclusion is:
"There are sufficient safety evaluation studies (both preclinical and clinical) to indicate the safety of KSM-66. Overall, the safety evaluation of the ashwagandha extract KSM-66 is based on (1) experience from the long history of use of traditional water extracts of ashwagandha roots and (2) quality control of the production of KSM-66, (3) preclinical safety evaluation studies on KSM-66, and (4) assessment of safety parameters in clinical trials with KSM-66."
- KSM66 has been included in a total of 39 clinical studies and 15 preclinical studies, of which 38 have been published or approved for publication while 16 are under review - in addition, 20 clinical studies are ongoing.
All journals are PubMed approved, which means that they are scientifically reviewed (peer-reviewed) and meet international standards.
- Nearly 4,000 men and women aged between 15 and 75 years were included in the studies, which together showed that the risk of experiencing an adverse reaction to KSM66 is comparable to placebo. All side effects have been mild and transient.
The majority of the clinical and preclinical studies did not exist in 2020 when DTU published its report.
In the report, DTU asks:
1. reproduction studies where animals were given ashwagandha continuously from mating to lactation
2. 90-day safety studies in animals.
3. long-term human study.
All these studies have now been completed at KSM66 - and published.
- In addition, Ixoreal has conducted a global, multicenter study of 1000 individuals and a high-dose study.
- KSM66 has been on the US market since 2013. 2.5 billion daily doses are consumed annually in 62 countries, 650 million of which are in Europe - making KSM66 one of the world's most widely used herbal supplements.
- In Sweden, more than 60 million daily doses have been sold since its launch in October 2017. No serious side effects have been reported with KSM66 in Sweden or in any other market.
- KSM66 is also one of the most certified food supplements in the world with 48 third-party certifications for traceability, environmental responsibility, safety and control. Certifications preferably issued by American, Korean and European certification bodies.
Conclusion: Malmö Stad miljöförvaltning has reviewed the safety documentation on KSM66 and based on this has concluded that there are no restrictions on KSM66.
Malmö 2025-10-21
Tom Johnsson, Founder, CEO, Quality Manager
MedicineGarden AB, tom@medicinegarden.se, 0705-94 91 95
The above is fact-checked by
Chief Physician, PhD Stefan Branth, Specialist in Internal Diseases and Clinical Nutrition, branthdr@gmail.com
All reports are available on request.
