In a recent systematic review published within 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 a whole bunch if not 1000’s of years. Nonetheless, a scientific review of the literature reveals only nine studies concerning the plant extracts’ anti-stress properties (mainly anti-cortisol), none of which were long-term. Nonetheless, this study highlights that for brief 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 traditional 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 necessity for protected interventions

Stress and its associated mental health comorbidities, including anxiety and depression, are a growing concern on this planet today. Research has identified that nearly 40% of humans are affected by the consequences of prolonged stress, 31% and 33% of which turn into anxiety or depression, respectively. The continued 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 often clinically measured in humans by evaluating the cortisol hormone level in an individual’s circulating blood plasma. Medical research has established that a rise or decrease in a person’s cortisol levels can form a reliable proxy for short-term stress, due to this fact making it the test of selection to watch patients undergoing anti-stress drug therapy.

Conventionally, chemicals used to treat stress include tranquilizers, beta-blockers, and selective serotonin reuptake inhibitors (SSRIs), a few of that 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 uncomfortable side effects and dependency on their prolonged use. Clubbed with the growing global popularization of self-administered ‘protected’ natural herbal medicines, this presents an urgent need for the invention of novel naturally-derived therapeutics that could be really helpful to the general public following their rigorous clinical testing.

Withania somnifera (WS) is a medicinal plant within the Solanaceae family. Called ‘Ashwagandha’ in the traditional Indian language of Sanskrit, ‘Indian ginseng’ in Ayurveda and traditional Chinese medicine, and ‘Winter cherry’ within 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 numerous 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. Nonetheless, 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 uncomfortable side effects.

Concerning the study

In the current 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. Greater than 4788 articles were included within the title and abstract screening, only nine of which passed full-text screening and were included within the review. Data extractions from these nine studies were conducted manually by a single reviewer to forestall 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 final result of interest was changes in cortisol levels (saliva or blood plasma) before and after WS extract administration.

Study findings

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. Nonetheless, the long-term effects of WS extracts, or the potential domino effect of reduced cortisol and adrenal hormone secretions, remain unknown. Not one of the included studies investigated the mechanisms underpinning the corticosteroid-suppressing ability of WS extracts.

Interestingly, only one in all the included studies referenced that the normal use of WS extracts in Ayurveda involved a posh combination of each Ashwagandha and other medicinal herbs, unlike the ‘only WS consumption’ paradigm of self-administration marketed today. Moreover, the WS extract concentrations utilized 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 discover ideal consumption dosages.