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Randomized Controlled Trial
. 2023 Nov;37(11):1091-1104.
doi: 10.1177/02698811231200023. Epub 2023 Sep 23.

Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial

Stephen J Smith  1   2 , Adrian L Lopresti  1   2 , Timothy J Fairchild  2
Affiliations
Randomized Controlled Trial

Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial

Stephen J Smith et al. J Psychopharmacol. 2023 Nov.

Abstract

Background: Stress is a state of homeostasis in the body being challenged, resulting in a systemic response. It has become more prevalent in recent years and affects mental and physical health.

Aims: Evaluate the effects of ashwagandha on stress, fatigue, and sex hormones in overweight or mildly obese men and women with self-reported stress and fatigue.

Methods: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40-75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily.

Results/outcomes: Supplementation with ashwagandha was associated with a significant reduction in stress levels based on the Perceived Stress Scale (primary outcome); however, the improvements were not significantly different to the placebo group (p = 0.867). Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group (p = 0.016), and participants taking ashwagandha also experienced a significant increase in heart rate variability (p = 0.003). However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of free testosterone (p = 0.048) and luteinizing hormone (p = 0.002) compared to the placebo group.

Conclusions/interpretation: The results of this study suggest that in overweight middle-to-older age adults experiencing high stress and fatigue, compared to the placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects. This may be via its impact on the autonomic nervous system. However, further research is required to expand on these current findings.

Keywords: Ashwagandha; Withania somnifera; fatigue; hormones; stress; testosterone.

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Conflict of interest statement

Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ALL is the managing director of Clinical Research Australia, a contract research organization that has received research funding from nutraceutical companies. ALL has also received presentation honoraria from nutraceutical companies. SJS is an employee of Clinical Research Australia and declares no other conflicts of interest. TJF declares no conflicts of interest.

Figures

Figure 1.
Figure 1.
Study design. CFS: Chalder Fatigue Scale; PROMIS-29: Patient-Reported Outcomes Measurements Information System—29; PSS: Perceived Stress Scale.
See this image and copyright information in PMC

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