Immunomodulatory Effect of Withania somnifera (Ashwagandha) Extract—A Randomized, Double-Blind, Placebo Controlled Trial with an Open Label Extension on Healthy Participants

Ajit Tharakan,Himanshu Shukla,Santhosh Koshy,Lekha George,Matthan Tharakan,Irin Rosanna Benny

doi:10.3390/jcm10163644

Abstract

The immunomodulatory effect of Withania somnifera (WS) extract was tested in healthy adults. In this randomized placebo-controlled double-blinded study, subjects were allocated either 60 mg WS extract or placebo. It consists of a blinded 30-day period and an open-label extension study of another 30 days with crossover of only placebo to test. After the 30-day blinded study period, the WS test group reported significant increase (p < 0.05) in Ig’s (IgA, IgM, IgG, IgG2, IgG3 and IgG4), Cytokines (IFN-γ, IL4), TBNK (CD45+, CD3+, CD4+, CD8+, CD19+, NK cells) whereas in the placebo group TBNK cells showed significant decrease (p < 0.05) and Ig’s and cytokines showed no change (p > 0.05). In the extension period on day 60, the subjects on placebo who were crossed over to the WS test group showed significant increase (p < 0.05) in Ig’s, cytokines and TBNK cells and the subjects who continued on the WS group showed a further significant improvement (p < 0.05) in Ig’s, cytokines and TBNK cells. There were no adverse events reported in the study. WS extract significantly improved the immune profile of healthy subjects by modulating the innate and adaptive immune systems. Boosting the immune system of people at risk of infection and during widespread infections can be targeted with WS extract.

Highlights

The mammalian immune system consists of three levels of defense: the physical barrier, the innate immune system, and the adaptive immune system [1]
The Withania somnifera (WS) extract used in our study showed a significant increase in CD3+, CD4+, CD8+, CD19+, and natural killer (NK) cells with 30 days of treatment
Future studies to address these limitations will help confirm these findings. This pilot, randomized, and controlled clinical study demonstrates for the first time that the leaf and root extract of WS standardized with withanolide glycosides possesses potent immune-stimulatory properties

Summary

Introduction

The mammalian immune system consists of three levels of defense: the physical barrier, the innate immune system, and the adaptive immune system [1]. Immunomodulators can be broadly classified into immunostimulants and immunosuppressants. Immunostimulants enhance the defense mechanisms and are used to prevent infections and cancer while immunosuppressants suppress the immune system and prevent autoimmune response and graft rejections. Immunomodulators of plant origin are a promising field of research and many potential candidates have been identified. Ashwagandha (Withania somnifera or WS) which is mentioned in the Rasayana group of medications in the Ayurveda tradition of India has been extensively investigated as an immunomodulatory agent. The components in WS mainly withanolide glycosides exert their immunomodulatory action by mobilizing and activating macrophages and induce proliferation in murine splenocytes [2]

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