Safety and Tolerability of <scp> <i>Withania somnifera</i> </scp> Root Extract in Healthy Male Participants: A Pilot Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

<i>Withania somnifera</i> (WS), also known as Ashwagandha in Ayurveda, is valued for its anti-inflammatory, antioxidant, adaptogenic, and memory-enhancing properties. This study assessed the safety of standardized Ashwagandha root extract in healthy adult participants over 180 days. A randomized, placebo-controlled, double-blind trial was conducted on 40 healthy adult participants (50-70 years), randomized 1:1 to receive 200 mg WS extract or placebo capsules twice daily for 180 days. Each WS capsule contained ≥ 5.00 mg of withanolides, standardized by HPLC-PDA per USP-NF monograph. Safety outcomes were assessed at screening and day 180. Hematological, hepatic, renal, and lipid profiles remained within normal ranges with no clinically significant changes compared to screening. Testosterone levels significantly increased (15.7%) in male participants in the WS group. Thyroid hormone levels, inflammatory marker (CRP), and NT-pro BNP levels showed no adverse changes. CRP decreased by 51.1%, and NT-pro BNP by 28.70% in the WS. Slight improvement in immunological markers (CD3, CD4, CD8) was also noted. The vital signs remained stable, with no clinical abnormalities detected on chest X-ray or ECG. Anthropometric parameters were not clinically changed after treatment. Taken together, the study concluded that WS root extract capsules (200 mg twice daily for 6 months) were well-tolerated and safe, with no adverse effects reported. This double-blind, placebo-controlled study with extended follow-up provides a comprehensive evaluation of the long-term safety profile of WS supplementation. <b>Trial Registration:</b> Clinical Trial Registry-India (CTRI) approval number: CTRI/2023/11/059395.