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

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.

Acute and Repeated Ashwagandha Supplementation Improves Markers of Cognitive Function and Mood

“…These findings are consistent with results from Chandrasekhar et al [ 6 ], who reported that ashwagandha supplementation (2 × 300 mg/d for 60 days) in individuals with a history of stress and anxiety had no clinically significant effects on clinical blood parameters or reported side effects. Additionally, results support findings from Smith and coworkers [ 18 ], who reported that 2 × 200 mg/d of ashwagandha root extract supplementation for 12 weeks in overweight men and women between the ages of 40–75 years experiencing high levels of fatigue and stress did not significantly affect blood glucose, HbA1c, cell blood counts, markers liver function, markers of renal function, or perceptions of side effects. Current findings also support other studies reporting that ashwagandha supplementation (500–700 mg/d for 2–8 weeks) in adults was well-tolerated and did not result in perceptions of side effects [ 33 , 64 , 70 , 71 ].…”

“…Ashwagandha has been reported to possess antioxidant [ 9 , 14 , 15 , 16 ], anti-inflammatory [ 9 , 11 , 12 ], neuroprotective [ 8 , 10 , 15 , 23 , 24 , 25 , 26 ], endocrinological [ 17 , 18 , 19 , 20 , 21 ], and immune-modulatory properties [ 10 , 22 ] that influence cognition [ 1 , 23 , 25 , 31 ]. Preliminary human clinical trials indicate that ashwagandha supplementation may have therapeutic benefits in individuals with medically managed bipolar disease [ 32 ], mild cognitive impairment [ 33 ], and chronic stress [ 7 ].…”

“…Since ashwagandha has antioxidant [ 9 , 14 , 15 , 16 ], endocrine [ 17 , 18 , 19 , 20 , 21 ], immune [ 10 , 22 ], and anti-inflammatory effects [ 9 , 11 , 12 ], there has been interest in determining the effects of ashwagandha supplementation on markers of health and safety. In this study, we assessed the effects of 30 days of ashwagandha supplementation on a comprehensive panel of whole blood and serum health markers and perceptions about the frequency and severity of common side effects.…”

“…Ashwagandha ( Withania somnifera ) is a plant used in Ayurvedic medicine for over 3000 years as a naturally occurring adaptogen to help manage stress, anxiety, and inflammation [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Ashwagandha has antioxidant properties [ 9 , 14 , 15 , 16 ], influences endocrine function [ 17 , 18 , 19 , 20 , 21 ], and has immunomodulatory effects [ 10 , 22 ]. Ashwagandha supplementation has been reported to attenuate cognitive decline associated with inflammation [ 9 , 11 , 12 ] and neurodegeneration [ 8 , 10 , 15 , 23 , 24 , 25 , 26 ].…”

Herbal-based Nutraceuticals in Management of Lifestyle Diseases: Experience from Indian Population

“…2). 16 A randomized controlled trial demonstrated that Ashwagandha root extract supplementation significantly re- Antioxidant; Anti-inflammatory duced stress, anxiety, and depression symptoms in individuals with chronic stress, highlighting its potential as a natural stress-management remedy. 17 A recent review explored the potential of Ashwagandha for managing stress and anxiety.…”