Written by Angeline A. De Leon, Staff Writer. Study findings suggest that ashwagandha’s stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis.

ashwagandha - botanicalsAshwagandha (Withania somnifera (L.) Dunal) is one of the most well-known herbs in Ayurvedic medicine, noted for its ability to bolster muscular strength and endurance and support general health 1. A wealth of studies support the anti-inflammatory, anti-oxidant, and immunomodulatory properties of ashwagandha 1,2, as well as its anxiolytic and antidepressant activities 3,4, as demonstrated in animal models of stress. More recent randomized, double-blind trials in humans also suggest that ashwagandha can modulate stress and anxiety 5,6, reducing subjective reports of stress, as well as cortisol (stress hormone) levels, serum C-reactive protein (CRP, biomarker of inflammation), pulse rates, and blood pressure in individuals with chronic stress 7. The cortisol-lowering, mood-enhancing effects of the medicinal herb have also been demonstrated in chronically stressed, overweight adults 8. Despite clear evidence of ashwagandha’s anxiolytic effects, its mechanisms of action are still under investigation and its efficacy over a longer study duration untested. Thus, in a 2019 trial 9published in Medicine, investigators sought to determine the effects and pharmacological actions of ashwagandha in adults with chronic stress over a 60-day trial period.

A total of 60 healthy individuals (aged 18-65 years) with self-report chronic stress (based on the Hamilton Anxiety Rating Scale, HAM-A) were enrolled in a randomized, double-blind, placebo-controlled trial. Subjects were randomized to ingest 240 mg of an ashwagandha extract (standardized to contain 35% withanolide glycosides) or placebo once daily for 15 days. At baseline and Day 60, morning blood samples were collected to assess dehydroepiandrosterone sulfate (DHEA-S, steroid hormone produced by adrenal glands), cortisol levels, and testosterone, and the self-report Depression, Anxiety, and Stress Scale-21 (DASS-21) was administered along with the HAM-A. On Days 15, 30, and 45, mood scales were re-administered, and on Day 30, cortisol and DHEA-S levels were measured.

In the ashwagandha group, HAM-A scores showed a significant reduction, relative to those of the placebo group, from baseline to Day 60 (from 10.27 +/- 0.59 to 6.07 +/- 0.38) (F4, 232= 2.55, p = 0.040). Ashwagandha supplementation, in comparison to placebo, also significantly reduced morning cortisol levels (from 14.15 +/- 0.94 to 10.84 +/- 1.04 mcg/dL) (F2, 116= 8.95, p < 0.001) and DHEA-S (from 218.93 +/- 28.93 to 201.08 +/- 27.41 mcg/dL) (F2, 116= 5.86, p = 0.004) from baseline to Day 60. Gender-wise analysis of testosterone levels revealed a statistically significant 11.4% increase in the testosterone levels of men (but not women) in the ashwagandha group (p = 0.038) over time, however, this change in hormone levels was not significant relative to placebo (p = 0.158).

Based on study findings, researchers conclude that daily intake of ashwagandha extract over the course of 60 days leads to significant improvements in emotional functioning, as seen through changes in mood scores as well as through reductions in biomarkers of stress. Coincident with an apparent positive (but not statistically significant) trend towards increasing testosterone concentrations, the decrease in cortisol and DHEA-S levels in the active treatment group suggests that the mechanisms associated with ashwagandha’s stress-relieving effects may involve a moderation of the hypothalamus-pituitary-adrenal axis (HPA), the central neuroendocrine system involved in the body’s stress response. Results of the current investigation shed light on the potential mechanisms underlying ashwagandha’s therapeutic efficacy and confirm its anxiolytic effects over a longer follow-up period. Potential study limitations should be considered, including the recruitment of a relatively limited sample size and the failure to account for individual dietary habits, economic conditions, and other lifestyle factors that could potentially impact therapeutic outcome. Future investigations are needed to more closely examine the link between changes in hormone levels and symptomology during ashwagandha supplementation.

Source: Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract. Medicine 2019;98:37(e17186).

© 2019 the Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Posted November 12, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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