Multicenter Trial Reports Safety Profile of KSM-66 Ashwagandha Over 8 Weeks

A trial published in Phytotherapy Research reports safety and tolerability data for KSM-66 Ashwagandha root extract in more than 1,000 adults, adding a large-sample dataset to the category.¹ The study was supplied by Ixoreal Biomed Inc., which highlighted the findings in a press release describing the trial as one of the largest prospective, placebo-controlled safety evaluations of an ashwagandha root extract conducted to date.²

“Scale is the point of this study,” stated Kartikeya Baldwa, Chief Executive Officer of Ixoreal Biomed Inc. “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 hematological markers.”

How Was the Study Designed?

The trial enrolled 1,002 adults aged 18 to 65 at 15 clinical sites across India, the United States, Australia, Portugal, and Africa. Participants received either 600 mg/day of KSM-66 Ashwagandha root extract, dosed as 300 mg twice daily, or a matched placebo, over 8 weeks. All participants completed the study and there were no losses to follow up.

The published study describes a prospective, multinational, multicenter, randomized, double-blind, placebo-controlled trial in adults with borderline to moderate stress and anxiety, defined by Hamilton Anxiety Rating Scale and Perceived Stress Scale criteria at screening. Of 1,286 individuals screened, 1,002 were randomized in a 1:1 ratio (498 to ashwagandha extract, 504 to placebo). Capsules were visually matched, and both participants and study personnel remained blinded throughout.

The primary outcome was safety, assessed through change in hematological and biochemical laboratory parameters from baseline to week 8, alongside monitoring for adverse events. Laboratory measures included white and red blood cell counts, hematocrit, hemoglobin, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine. Tolerability, a secondary outcome, was assessed using the Global Assessment of Tolerability to Therapy (GATT) scale.

What Did the Study Find?

Laboratory data were available for a subset of 892 participants. No statistically or clinically significant between-group differences were found in hematological or biochemical parameters, and values for both groups remained within normal physiological ranges at baseline and week 8.

No serious adverse events were reported in either arm. A total of 74 adverse events (7.4%) were reported, with 46 (9.2%) in the placebo group and 28 (5.6%) in the extract group. The most frequently reported events were nausea, dry mouth, and headache, all described as mild to moderate. On the GATT scale, 88.2% of participants receiving the extract and 89.1% of those receiving placebo rated the therapy as "Good" or "Excellent," with no statistically significant difference between groups.

What Are the Study's Limitations?

The study authors identified several limitations. The eight-week duration restricts conclusions about long-term safety. Paired laboratory data were incomplete for a portion of participants, and the panel relied on standard biochemical markers without more advanced biomarkers. The authors also noted that the primary statistical approach emphasized within-group changes from baseline rather than direct between-group comparisons, meaning causal claims about comparative safety should be made cautiously. Additionally, roughly 80% of participants were recruited in India, which the authors said may limit generalizability to other populations.

What Other Research Has Ixoreal Published Recently?

Ixoreal has also reported on SRI-81 Shatavari, a standardized root extract for perimenopausal support. An 8-week, randomized, double-blind, placebo-controlled trial in 80 women aged 40 to 55 found statistically significant improvements versus placebo in total Menopause Rating Scale score and all three subdomains, along with reduced hot-flash frequency and lower perceived stress.³ No adverse events, including changes in liver or kidney function, were reported.

References

1. Pakhale K, Salve J, Ademola J, Parraca J, Langade D. 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. Phytother Res. 2026;40(8):5005-5015. doi:10.1002/ptr.70315
2. Ixoreal Biomed Inc. One of the largest ashwagandha trials to date finds KSM-66 Ashwagandha well tolerated in 1,002 adults, with laboratory safety markers within normal range. September 1, 2026. Accessed September 9, 2026.
3. Mahajan S, Avad P, Langade J. Efficacy and safety of Shatavari (Asparagus racemosus) root extract for perimenopause: randomized, double-blind, placebo-controlled study. Int J Womens Health. 2025;17:4057-4073. doi:10.2147/IJWH.S544267