4. Discussion
aggression, depression, toxicity, anxiety
INFLAMMATION
In this randomized double-blind, placebo-controlled study, consumption of 500 mg ARE (Shagandha) with 5 mg piperine for 60 days significantly improved the stress and anxiety symptoms in individuals with mild to moderate stress and anxiety, The Stress (PSS) and anxiety (GAD-7) scores improved in all the participants taking ARE while only 40% and 20% of the participants showed an improvement in stress and anxiety respectively in placebo. The quality of life of the participants improved significantly with ARE supplementation.The anti-stress and anxiolytic activity of ashwagandha has been evaluated earlier in healthy participants, individuals with obesity-related stress, work stress, and stress associated with anxiety in different clinical studies.It is well-documented that anxiety affects cognitive performance,To understand the possible mechanism of ARE action, we evaluated salivary cortisol, as a stress marker. Salivary cortisol is known to be a valuable indicator of the hypothalamic-pituitary-adrenocortical axis activity, and its concentration was found to be directly proportional to the biologically active serum unbound cortisol concentration.Serotonin (5-hydroxytryptamine, 5-HT) is a major neurotransmitter that plays a role in the maintenance of circadian rhythm, appetite, aggression, sensorimotor activity, mood, cognition, learning, and memory.Dopamine is another central nervous system neurotransmitter that is involved in reducing depression. The association of dopamine with stress is complex as stress-induced elevations in cortisol levels have been directly correlated with amphetamine-induced dopamine release and administration of corticotrophin-releasing hormone was found to result in dopamine release.Stress-induced production of nitric oxide in the hippocampus can negatively alter adaptation to stress and can induce cellular toxicity by generating free radicals.Apart from these pathways, Ashwagandha supplementation was shown to reduce serum dehydroepiandrosterone sulfate in stressed adults.A few limitations of the study are worth mentioning. The study was carried out in healthy adults, with mild to moderate stress in southern India. Future studies in different ethnic populations with different degrees of anxiety and stress would be helpful. The present study examined the effect of ARE for 60 days in a relatively small population of 54 participants. Studies in a larger population and longer duration of supplementation and follow-up after termination will also help to understand the sustained effects of ARE in relieving stress and anxiety. The physiological response to stress and anxiety involved multiple, interdependent pathways. Future studies including the effect of ARE on the HPA axis, inflammation, and other hormones would delineate the mechanism of action of the supplement.