Superior Bioavailability of a Novel 1.5% Ashwagandha Formulation (Zenroot™): A Randomized, Double-Blind, Single-Dose, Comparative, Oral Bioavailability Study in Healthy Adults.

INTRODUCTION

Ashwagandha has multiple medicinal properties and is widely used as a supplement to address various health conditions including stress and anxiety. The bioavailability of Ashwagandha bioactives provide critical information on the biological effects in humans after oral supplementation.

METHODS

A randomized, double-blind, single-dose, cross-over comparative oral bioavailability study was conducted in 20 healthy, adult human subjects under fasting conditions. All subjects consumed single dose of ZEN 1.5 (Zenroot™ Ashwagandha 1.5% 125 mg), ASH 5 (Reference product 1-Ashwagandha 5% 600 mg) and ASH 10 (Reference product 2-Ashwagandha 10% 500 mg) as per a randomization schedule. Blood samples were collected at 0.00 h, and at 00.25, 00.50, 00.75, 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 09.00, 12.00, and 24.00 h post-dose. Total withanolides (consisting of withanoside IV, withanolide A, 12-deoxywithastramonolide, and withaferin A) were quantified in plasma using the LC-MS/MS method and pharmacokinetics parameters like area under the curve, AUC, C, T, t and test/reference (T/R) ratio for test product, ZEN 1.5, versus reference products, ASH 5 and ASH 10, were used for statistical comparisons.

RESULTS

Subjects in the ZEN 1.5 group showed significantly (P < 0.05) higher total withanolides concentration in plasma at all post-dose time points except 12.00 and 24.00 h compared to ASH 5. In addition, subjects in Ashwagandha ZEN 1.5 group showed significantly higher (P < 0.05) total withanolides concentration in plasma at 0.25, 1.00, 2.00, 3.0, and 4.00 h compared to ASH 10. Further, ZEN 1.5 showed significantly higher bioavailability for total withanolides compared to ASH 5 and ASH 10 with significantly higher (P < 0.05) C and AUC parameters, T/R ratio, and 90% CI. ZEN 1.5 at 125-mg dose showed 2.1-fold higher bioavailability compared to ASH 5 at 600 mg, and 1.3-fold higher bioavailability compared to ASH 10 at 500 mg. ZEN 1.5 was well tolerated during the study period.

CONCLUSION

A low dose of 125 mg of ZEN 1.5 showed greater total withanolides bioavailability compared to reference products. The C and AUC parameters were significantly higher than the 80-125% criteria established by the FDA for bioequivalence confirming superior bioavailability of ZEN 1.5. In addition, ZEN 1.5 was well tolerated by subjects throughout the study duration. Further studies are warranted for evaluating the health benefits of ZEN 1.5.

TRIAL REGISTRATION

CTRI/2022/11/047039.