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

Abstract

Ashwagandha (Withania somnifera) has been recognized for enhancing physical strength, mental well-being, and overall vitality. Despite its long-standing use across generations, some clinical reports have noted occasional adverse events. This study compared the safety and tolerability of Ashwagandha Root Extract (ARE) in healthy adults. This was a prospective, multicenter, multinational, randomized, double-blinded, placebo-controlled study (n = 1002; 18 to 65 years). Participants with reported stress and anxiety were randomly assigned to receive either 600 mg/day (two divided doses) of ARE (n = 498) or a placebo (PL, n = 504) orally for 8 weeks. The primary outcome was the safety profile assessed through laboratory parameters and adverse events (AEs), while tolerability was assessed by the participants on a 7-point Likert scale of Global Assessment of Tolerability to Therapy. Demographic and baseline characteristics were similar between groups. No serious adverse events were reported; a total of 74 AEs (7.4%) were documented, with 46 events (9.2%) in the PL group and 28 events (5.6%) in the ARE group. The most common AEs include nausea (3.2% in PL vs. 2.0% in ARE), dry mouth (1.4% in both groups), and headache (2.2% in PL vs. 0.2% in ARE). Laboratory evaluations showed no significant changes in liver function tests, renal function markers, or hematological parameters between the ARE and PL groups. Both groups maintained normal ranges for key biomarkers, including aspartate aminotransferase, alanine aminotransferase, creatinine, and hemoglobin levels throughout the study duration. Tolerability ratings showed no statistically significant difference between the groups (p = 0.487), and most of the participants rated the ARE therapy as "Good" or "Excellent." ARE is well-tolerated and safe in adults with stress and anxiety. These results support the use of Ashwagandha root extract as a viable non-pharmacological treatment, warranting further exploration of its long-term effects in diverse populations.

Keywords: Withania somnifera; Ashwagandha; anxiety; safety; stress.