Randomized, Double-Blind, Crossover Study Comparing the Bioavailability of 4 Ashwagandha (Withania somnifera (L.) Dunal) Extracts in Healthy Adults Under Fasting Condition
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Purpose Withania somnifera (L.) Dunal, commonly known as ashwagandha, is a well-known plant in Ayurvedic medicine, widely valued for its therapeutic potential. Although numerous clinical studies have explored its diverse health benefits, limited data are available on the pharmacokinetics and comparative bioavailability of its key bioactive constituents in humans. This study aimed to evaluate and compare the oral bioavailability of four commercially standardized ashwagandha extracts under fasting conditions in healthy adults. Methods This randomized, double-blind, four-treatment, four-period, four-sequence, single dose, four-way crossover study was conducted in 16 healthy human volunteers. Participants received a single oral dose of one of four ashwagandha extracts, with varying compositions of 35% (WS-35) and 10% (WS-10) withanolide glycosides, 5% (WS-5) and 2.5% (WS-2.5) withanolides, each standardized to deliver 185 mg of total withanolides, Seventeen blood samples were collected over 24-hour period post dose. Plasma concentrations of Withanolide A, Withanoside IV, Withaferin A, and total withanolides were quantified and pharmacokinetic parameters were calculated. Findings WS-35 demonstrated significantly superior bioavailability compared to the other extracts. The AUC 0-t for total withanolides per gram of WS-35 was 118.28, 226.11 and 267.83 times better than WS-10, WS-5 and WS-2.5 respectively. WS-35 exhibited a significantly higher C-max, longer half-life, extended mean residence time and lower systemic clearance, attributable to its higher withanolide glycoside content. Implications These findings emphasize the critical role of withanolide glycosides in determining the pharmacokinetic performance of ashwagandha supplements. The enhanced bioavailability of WS-35 supports its preferential use in therapeutic applications and provides a strong rationale for further investigation into dose-response relationships and the long-term efficacy of standardized, high-bioavailability formulations. Trial registration CTRI/2020/10/028397 [Registered on: 13/10/2020] http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=42149&EncHid=&userName=CTRI/2020/10/028397
Source: Current Therapeutic Research
Authors: Priyank Rathi, Se-Kwon Kim
Institution: Hanyang University
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W4412458311