In a recent systematic review published in the journal Nutrients, researchers collated and investigated available literature testing the cortisol-associated function of Withania somnifera. Colloquially called 'Ashwagandha' in India, the plant's medicinal values have been assumed for hundreds if not thousands of years. However, a systematic review of the literature reveals only nine studies about the plant extracts' anti-stress properties (mainly anti-cortisol), none of which were long-term. Nonetheless, this study highlights that for short durations of time, W. somnifera extracts used under medical supervision have a suppressive impact on cortisol hormone secretions, presenting the plant as a natural, cost-effective, and side-effect-free alternative to conventional chemical clinical interventions.
Study: Effects of Withania somnifera on Cortisol Levels in Stressed Human Subjects: A Systematic Review. Image Credit: Azay photography / Shutterstock
Stress and the need for safe interventions
Stress and its associated mental health comorbidities, including anxiety and depression, are a growing concern in the world today. Research has identified that almost 40% of humans are suffering from the effects of prolonged stress, 31% and 33% of which develop into anxiety or depression, respectively. The ongoing coronavirus disease 2019 (COVID-19) has severely exacerbated this already worrisome trend, with the World Health Organization estimating a 25% increase in baseline stress levels globally as a consequence of the pandemic.
Stress is usually clinically measured in humans by evaluating the cortisol hormone level in a person's circulating blood plasma. Medical research has established that an increase or decrease in an individual's cortisol levels can form a reliable proxy for short-term stress, therefore making it the test of choice to monitor patients undergoing anti-stress drug therapy.
Conventionally, chemicals used to treat stress include tranquilizers, beta-blockers, and selective serotonin reuptake inhibitors (SSRIs), some of which are extremely expensive and inaccessible to socioeconomically deprived patients. A growing body of literature further highlights that these chemicals, while effective in treating stress and mental disorders, have a high risk of side effects and dependency on their prolonged use. Clubbed with the growing global popularization of self-administered 'safe' natural herbal medicines, this presents an urgent need for the discovery of novel naturally-derived therapeutics that can be recommended to the public following their rigorous clinical testing.
Withania somnifera (WS) is a medicinal plant in the Solanaceae family. Called 'Ashwagandha' in the ancient Indian language of Sanskrit, 'Indian ginseng' in Ayurveda and traditional Chinese medicine, and 'Winter cherry' in the West, this plant is native to India, the Middle East, and parts of Africa. WS has been considered a medicinal plant in traditional medicine, with records of its use in India going back 2500 years. The plant's extracts have been used to treat a number of unrelated diseases, including arthritis, insomnia, tuberculosis (TB), asthma, male infertility, and anxiety.
Scientific research has verified several traditional applications of WS extracts, including male infertility and improved thyroid regulation. However, while evidence exists for the positive effects of WS impacts on stress and cortisol levels, the mechanisms governing this interaction remain unknown, with little to no literature exploring the long-term effects of WS extract consumption or the potential for side effects.
About the study
In the present study, researchers systematically reviewed all available scientific literature on the associations between WS interventions and stress outcomes. They collated publications from five scientific repositories, which were filtered and analyzed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Methodologies and the review were registered with the database of prospectively registered systematic reviews in health and social care (PROSPERO).
Data collection comprised perusing PubMed, EMBASE, Scopus, Google Scholar, and CENTRAL from database initiation till 16 May 2023. More than 4788 articles were included in the title and abstract screening, only nine of which passed full-text screening and were included in the review. Data extractions from these nine studies were conducted manually by a single reviewer to prevent reviewer bias.
Eight included studies were found to be short-term, double-blind studies following similar methodologies, while the ninth was a controlled trial with a crossover study design. In all studies, participants were healthy at study onset, and the outcome of interest was changes in cortisol levels (saliva or blood plasma) before and after WS extract administration.
Corroborating previous work, the consumption of WS extracts for between 30 and 112 days resulted in measurable and significant reductions in cortisol levels in study participants. However, the long-term effects of WS extracts, or the potential domino effect of reduced cortisol and adrenal hormone secretions, remain unknown. None of the included studies investigated the mechanisms underpinning the corticosteroid-suppressing ability of WS extracts.
Interestingly, only one of the included studies referenced that the traditional use of WS extracts in Ayurveda involved a complex combination of both Ashwagandha and other medicinal herbs, unlike the 'only WS consumption' paradigm of self-administration marketed today. Furthermore, the WS extract concentrations used in the included studies were orders of magnitude (grams) higher than that included in most over-the-counter self-help drugs (milligrams at most), prompting studies to identify ideal consumption dosages.