High-Dose Ashwagandha Root Extract Demonstrates Safety and Tolerability in Clinical Trial

A new clinical trial published in Frontiers in Nutrition has established a favorable safety and tolerability profile for Ashwagandha (Withania somnifera) root extract at a high dose of 2,000 mg/day.¹ This amount is greater than the commonly studied therapeutic dose of 600 mg/day, notes Ixoreal Biomed Inc., stating that this study marks the highest dose safety evaluation of a standardized ashwagandha extract.² The prospective, single-arm, non-comparative study monitored healthy adults over a 12-week period to evaluate the impact of this increased dosage on primary organ systems.

Traditionally, the adaptogenic herb is used to increase stress resilience and improve overall wellbeing, the study explains.

Key Clinical Results and Findings

The study evaluated an intent-to-treat (ITT) population of 145 healthy male and female participants aged 18–65, with 124 individuals completing the full 12-week protocol. Participants received 500 mg capsules of a standardized ashwagandha root extract (KSM-66, manufactured by Ixoreal Biomed Inc.) taken orally twice daily, resulting in a total daily dose of 2,000 mg.

The primary safety outcomes focused on comprehensive laboratory monitoring of hepatic, renal, and thyroid functions. Blood samples collected at baseline, week 4, week 8, and week 12 revealed that all laboratory parameters remained within normal reference limits.

• Hepatic Parameters: Statistically significant decreases from baseline occurred in total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST/SGOT), and alanine aminotransferase (ALT/SGPT). A small but statistically significant increase was noted in alkaline phosphatase. However, no clinically meaningful changes were observed, and all values remained within established reference ranges.
• Renal Parameters: Serum creatinine and blood urea nitrogen (BUN) both demonstrated statistically significant reductions from baseline to week 12, remaining fully within normal clinical limits.
• Thyroid Profile: Small but statistically significant decreases were observed in thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), with no indicators of clinical dysfunction.

No serious adverse events were reported during the study and none of the findings indicated hepatic, renal, or thyroid dysfunction. Within the safety population, 85.5% of participants experienced no adverse events at all. 21 participants (14.5%) experienced at least one adverse event. The reported side effects were mild, transient, and resolved without medical intervention, with mild nausea being the most common (5.5%), followed by abdominal pain (3.4%), drowsiness (2.1%), and dizziness (2.1%). No participants withdrew from the trial due to safety concerns.

Secondary exploratory outcomes assessed quality of life (QoL) via the SF-36 questionnaire. The per-protocol population exhibited statistically significant improvements in physical functioning, role limitations due to physical health, social functioning, and pain. Subgroup analyses indicated that women experienced greater quality-of-life enhancements compared to men. However, Ixoreal Biomed also noted that the secondary results should not be considered evidence of treatment effect because the study was not designed to measure efficacy of the extract.

The researchers note that limitations to the observational study include a lack of direct comparison from a placebo, and that the findings establish a foundation for long-term and efficacy studies.

Implications for the Nutraceutical Industry

These findings offer utility for the dietary supplement market. As consumer demand for functional botanicals drives the formulation of concentrated extracts, creating robust safety data at higher exposure levels becomes essential.

Kartikeya Baldwa, CEO of Ixoreal Biomed Inc., noted that this study builds on existing safety data. "KSM-66 Ashwagandha has an established safety record at the standard 600 mg/day dose across multiple rigorous clinical trials,” he explains. “This study takes that evidence meaningfully further. Even at 2,000 mg/day over a 12-week period, KSM-66 was well tolerated, with no clinically significant changes observed in liver, kidney, or thyroid function in this group of healthy adults. For brands and formulators evaluating high-potency formats, these are encouraging safety data.” The company also highlighted that the extract is the subject of more than 100 studies across stress, sleep, cognition, endurance, and hormonal health.

This article was created with assistance from AI. The content has been reviewed and edited by Erin McEvoy, Associate Editor. For more information on the extent and nature of AI usage, please contact us.

References

1. Movva N, Salve J, Debnath K, Thakare V, Langade D. Safety and tolerability of Ashwagandha (Withania somnifera) root extract in healthy adults: a prospective, non-comparative study. Front Nutr. 2026;13:1823678. doi:10.3389/fnut.2026.1823678
2. Ixoreal Biomed Inc. KSM-66 Ashwagandha shows favorable safety and tolerability at 2,000 mg/day in first high-dose clinical study, new peer-reviewed data show. Press release provided via email June 8, 2026. Accessed June 9, 2026.