Published in Phytotherapy Research, the randomized, double-blind, placebo-controlled trial involved 1,002 adults and concluded Ixoreal Biomed Inc’s KSM-66 root extract was well tolerated over eight weeks, based on laboratory measures of liver function, renal function and haematological parameters.
No serious adverse events were reported in either group and most participants rated tolerability as excellent or good.
Investing in safety
The research comes at a time when the safety of ashwagandha is being called into question by authorities across Europe and India.
Concerns raised by regulators relate to thyroid effects, liver injury reports, reproductive effects and variable extract quality, prompting a ban in Denmark, attempted restrictions in India, and an ongoing discussion about potential EU-wide measures.
Kartikeya Baldwa, chief executive officer at Ixoreal Biomed Inc, told NutraIngredients his company has spent tens of millions of dollars documenting the safety of KSM-66 Ashwagandha across more than 15 clinical studies measuring liver function, thyroid hormones, sex hormones, kidney function and hematology.
“Scale is the point of this study,” he said. “Safety questions about ashwagandha have been argued largely on small studies and individual case reports. This trial adds one of the largest controlled datasets in the category, and what it records is high participant-rated tolerability, no serious adverse events, and no clinically significant shift in liver, renal or haematological markers.”
The company additionally has a 12-month long-term safety study as well as a high-dose 12-week study at 2,000 mg/day, indicating safety at more than three times the recommended dosage.
“Several of these were built around safety as the primary endpoint rather than measuring it alongside an efficacy question,” added Baldwa. “These beside the complete battery of toxicological studies, as per EFSA guidelines, make KSM-66 ashwagandha root extract one of the most studied ashwagandha extracts for safety.”
Discussing the regulatory uncertainty, Baldwa added: “We are confident that with the given body of wide evidence on the safety, ashwagandha root will remain legal across the globe.”
Dr. Thomas Brendler, botanical product expert and consultant and founder of Plantaphile, has been collating the body of evidence to support ashwagandha’s safety, recently presenting his initial analysis in a meeting at the European Parliament.
He said this KSM-66 study provides “an important puzzle piece” as it fills a gap in the safety evidence for the herb.
Noting that his own investigations indicate well-documented preparations of ashwagandha in the marketplace do not show clear safety superiority or inferiority, he argued the KSM-66 study is “largely applicable for a broad spectrum of clinically tested ashwagandha preparations”.
Well tolerated intervention
Conducted by researchers from universities and research institutes in India and Portugal and the US, the large scale KSM-66 study enrolled 1,002 adults aged 18 to 65 at clinical sites in India, the United States, Australia, Portugal and Africa.
Participants received either 600 mg/day of KSM-66 Ashwagandha root extract, given as 300 mg twice daily, or a matched placebo. Every participant completed the study.
The primary outcome was safety, assessed through change in laboratory parameters from baseline to week eight through adverse event monitoring. Tolerability was assessed as a secondary outcome, rated by participants on the seven-point Global Assessment of Tolerability to Therapy scale. The authors reported both the adverse event data and the tolerability ratings indicate the extract was as well tolerated as placebo.
Liver function markers, including aspartate aminotransferase and alanine aminotransferase, remained within normal physiological ranges in both groups, as did creatinine and haematological parameters including white and red blood cell counts, haemoglobin, haematocrit and platelet count.
Noted study limitations include its relatively short duration and the limited representation from non-Indian populations which may affect the generalizability of the findings across diverse ethnic groups.
Source: Phytotherapy Research. doi: https://doi.org/10.1002/ptr.70315. “Safety of 8-Week Administration With Ashwagandha (Withania somnifera) Root Extract in Adults With Stress and Anxiety: Findings From a Prospective, Randomized, Multi-Center, Double-Blinded, Placebo-Controlled Study.” Authors: K. Pakhale, et al.
