Efficacy and safety of Ashwagandha (Withania somnifera) root extract on stress and weight management in adults: a prospective, randomized, double-blind, placebo-controlled study

Abstract

The relationship between excess body weight and stress significantly impacts overall health. The current study evaluated the efficacy and safety of Ashwagandha (Withania somnifera) root extract (ARE) in altering stress biomarkers and its role in weight management. In this prospective, randomized, double-blind, placebo-controlled study, 100 participants (age: 19-65 years) were randomized to receive either ARE 300 mg twice daily (n = 50) or an identical placebo (PL, n = 50) for 24 weeks. The primary efficacy endpoints were changes in body weight and body mass index (BMI). Secondary endpoints included evaluation of stress (Perceived Stress Scale, PSS), quality of life (Short Form-12 Quality of Life Scale), subjective satisfaction (Subjective Satisfaction Scale, SSS), and food cravings (Food Cravings Questionnaire-Trait, FCQ-T). Clinical safety was assessed based on treatment-emergent adverse events (TEAEs) and laboratory parameters, including complete blood count, renal function tests, liver function tests, lipid profile, thyroid function tests, and glycemic parameters (plasma glucose and glycated hemoglobin). Efficacy was analyzed in 91 patients. ARE administration resulted in a significant reduction in body weight (-8.46 ± 3.86 kg; P < 0.0001) and BMI (-3.31 ± 1.57 kg/m²; P < 0.0001) compared to the PL (-2.41 ± 2.07 kg and -0.93 ± 0.79 kg/m² for body weight and BMI, respectively). Compared with PL, ARE showed significant improvements (P < 0.05) in PSS, SF-12, SSS, and FCQ-T scores. A total of seven participants with ARE and six with PL reported mild adverse events (nausea, abdominal pain, and drowsiness), which were resolved without any intervention. Ashwagandha root extract may offer a safe and beneficial approach for stress reduction and weight management.

Keywords: AEs, adverse events; ANOVA, analysis of variance; ARE, Ashwagandha root extract; BMI, body mass index; CA2, carbonic anhydrase II; CA3, carbonic anhydrase III; CBC, complete blood count; CLIA, chemiluminescent immunoassay; CONSORT, Consolidated Standards of Reporting Trials; CTRI, Clinical Trials Registry of India; FCQ-T, Food Cravings Questionnaire-Trait; GLM, General Linear Model; HPA, hypothalamic-pituitary-adrenal axis; ICH-GCP, International Council for Harmonisation Good Clinical Practice; IEC, Institutional Ethics Committee; LFT, liver function tests; MCS, Mental Component Summary; PCS, Physical Component Summary; PL, placebo; PSS, Perceived Stress Scale; RCT, randomized controlled trial; SD, standard deviation; SSS, Subjective Satisfaction Scale; T3, triiodothyronine; T4, thyroxine; TEAEs, treatment-emergent adverse events; Withania somnifera; overweight; psychological; safety; stress.