{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:12:10Z","timestamp":1779340330148,"version":"3.51.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>Ashwagandha, adaptogenic herb traditionally used to enhance resilience to stress and promote overall well-being. Although its safety at conventional doses is well established, evidence regarding the safety of higher doses in healthy adults remains limited. The present study aimed to evaluate the safety and tolerability of Ashwagandha root extract (ARE) administered at a dose of 2000\u202fmg\/day in healthy adults over 12\u202fweeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a prospective, single-arm, non-comparative clinical study conducted in healthy adults aged 18\u201365\u202fyears. Participants received ARE 500\u202fmg capsules (total daily dose of 2000\u202fmg) orally for 12\u202fweeks. Primary safety outcomes included laboratory evaluations of renal, hepatic, and thyroid parameters. Secondary safety outcomes included clinical assessment of adverse events and changes in quality of life assessed using the SF-36 questionnaire.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over 12\u202fweeks, minor changes (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05) occurred in serum bilirubin, alkaline phosphatase, creatinine, transaminases, blood urea, and thyroid parameters in PP dataset (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f124) who completed study. All values remained within reference ranges and were clinically insignificant, with most values slightly reduced except a small increase in alkaline phosphatase. No serious or clinically significant changes were noted. In ITT dataset (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f145) most participants (85.5%) experienced no adverse events, with mild nausea being the most common at 5.5%. Quality of life (SF-36 scores) demonstrated improvement (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05) after 12\u202fweeks in the SF-36 domains of physical functioning, role limitations due to physical health, social functioning, and pain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>High-dose Ashwagandha root extract (2000\u202fmg\/day) was well tolerated and demonstrated a favourable safety profile in healthy adults over 12\u202fweeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>https:\/\/ctri.nic.in\/Clinicaltrials\/pmaindet2.php?EncHid=ODE3NTk=&amp;amp;Enc=&amp;amp;userName=<\/jats:uri>\n                      , Identifier (CTRI\/2023\/04\/051607).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1823678","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:50:57Z","timestamp":1779339057000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and tolerability of Ashwagandha (Withania somnifera) root extract in healthy adults: a prospective, non-comparative study"],"prefix":"10.3389","volume":"13","author":[{"given":"Navya","family":"Movva","sequence":"first","affiliation":[{"name":"Department of Pharmacology, D. Y Patil University School of Medicine","place":["Navi Mumbai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaysing","family":"Salve","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Prakruti Care Hospital","place":["Thane, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khokan","family":"Debnath","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Prakruti Care Hospital","place":["Thane, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishali","family":"Thakare","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, D. Y Patil University School of Medicine","place":["Navi Mumbai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Langade","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, D. Y Patil University School of Medicine","place":["Navi Mumbai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.3390\/pharmaceutics15041057","article-title":"Ashwagandha (Withania somnifera)\u2014current research on the health-promoting activities: a narrative review","volume":"15","author":"Mikulska","year":"2023","journal-title":"Pharmaceutics"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"102642","DOI":"10.1016\/j.ctim.2020.102642","article-title":"Safety of Ashwagandha root extract: a randomized, placebo-controlled study in healthy volunteers","volume":"57","author":"Verma","year":"2021","journal-title":"Complement Ther Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S0378-8741(98)00107-X","article-title":"Antistressor effect of Withania somnifera","volume":"64","author":"Archana","year":"1998","journal-title":"J Ethnopharmacol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.4103\/0253-7176.106022","article-title":"A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root in reducing stress and anxiety in adults","volume":"34","author":"Chandrasekhar","year":"2012","journal-title":"Indian J Psychol Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e5797","DOI":"10.7759\/cureus.5797","article-title":"Efficacy and safety of Ashwagandha (Withania somnifera) root extract in insomnia and anxiety: a double-blind, randomized, placebo-controlled study","volume":"11","author":"Langade","year":"2019","journal-title":"Cureus"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.3390\/molecules14072373","article-title":"Steroidal lactones from Withania somnifera, an ancient plant for novel medicine","volume":"14","author":"Mirjalili","year":"2009","journal-title":"Molecules"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"442","DOI":"10.32383\/farmpol\/127824","article-title":"Ashwagandha (Withania somnifera L.)\u2014the plant with proven health-promoting properties","volume":"76","author":"Po\u0142umackanycz","year":"2020","journal-title":"Farm Pol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"320","DOI":"10.4297\/najms.2011.3320","article-title":"Immune enhancing effects of WB365, a novel combination of Ashwagandha (Withania somnifera) and Maitake (Grifola frondosa) extracts","volume":"3","author":"Vetvicka","year":"2011","journal-title":"North Am J Med Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/1472-6882-11-65","article-title":"High catechin concentrations detected in Withania somnifera (Ashwagandha) by high performance liquid chromatography analysis","volume":"11","author":"Alam","year":"2011","journal-title":"BMC Complement Altern Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1007\/s11101-017-9504-6","article-title":"Withania somnifera (Linn.) Dunal: a review of chemical and pharmacological diversity","volume":"16","author":"Kalra","year":"2017","journal-title":"Phytochem Rev"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"623795","DOI":"10.3389\/fphar.2021.623795","article-title":"Withania somnifera (L.) Dunal: opportunity for clinical repurposing in COVID-19 management","volume":"12","author":"Saggam","year":"2021","journal-title":"Front Pharmacol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"576962","DOI":"10.1093\/ecam\/nep138","article-title":"Withania somnifera improves semen quality in stress-related male fertility","volume":"2011","author":"Mahdi","year":"2011","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1177\/1534735412464551","article-title":"Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy-induced fatigue and quality of life in breast cancer patients","volume":"12","author":"Biswal","year":"2013","journal-title":"Integr Cancer Ther"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/19390211.2020.1741484","article-title":"Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects","volume":"18","author":"Mandlik","year":"2021","journal-title":"J Diet Suppl"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"113157","DOI":"10.1016\/j.jep.2020.113157","article-title":"Withania somnifera (L.) Dunal\u2014modern perspectives of an ancient Rasayana from Ayurveda","volume":"264","author":"Mukherjee","year":"2021","journal-title":"J Ethnopharmacol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"208","DOI":"10.4314\/ajtcam.v8i5S.9","article-title":"An overview on Ashwagandha: a Rasayana (rejuvenator) of Ayurveda","volume":"8","author":"Singh","year":"2011","journal-title":"Afr J Tradit Complement Altern Med"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12970-015-0104-9","article-title":"Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial","volume":"12","author":"Wankhede","year":"2015","journal-title":"J Int Soc Sports Nutr"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1080\/19390211.2017.1284970","article-title":"Efficacy and safety of Ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions","volume":"14","author":"Choudhary","year":"2017","journal-title":"J Diet Suppl."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"11852","DOI":"10.3390\/ijerph191911852","article-title":"Effects of acute Ashwagandha ingestion on cognitive function","volume":"19","author":"Xing","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.ejca.2009.01.034","article-title":"Immune modulation and apoptosis induction: two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera","volume":"45","author":"Malik","year":"2009","journal-title":"Eur J Cancer"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.jep.2016.07.080","article-title":"Network ethnopharmacological evaluation of the immunomodulatory activity of Withania somnifera","volume":"197","author":"Chandran","year":"2017","journal-title":"J Ethnopharmacol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"112768","DOI":"10.1016\/j.jep.2020.112768","article-title":"Safety and clinical effectiveness of Withania somnifera (Linn.) Dunal root in human ailments","volume":"255","author":"Tandon","year":"2020","journal-title":"J Ethnopharmacol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/j.pnpbp.2007.09.011","article-title":"Withania somnifera: an Indian ginseng","volume":"32","author":"Kulkarni","year":"2008","journal-title":"Prog NeuroPsychopharmacol Biol Psychiatry"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"148","DOI":"10.4103\/ijar.ijar_192_24","article-title":"Ashwagandha under fire: a critical scientific analysis of regulatory decisions","volume":"5","author":"Chernigoy","year":"2024","journal-title":"Int J Ayurveda Res"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"100859","DOI":"10.1016\/j.jaim.2023.100859","article-title":"Clinical safety and tolerability evaluation of Withania somnifera (L.) Dunal (Ashwagandha) root extract in healthy human volunteers","volume":"15","author":"Vaidya","year":"2024","journal-title":"J Ayurveda Integr Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1767865","DOI":"10.3389\/fgwh.2026.1767865","article-title":"Efficacy and safety of Ashwagandha (Withania somnifera) root extract in pregnant women: a prospective, randomized, comparative, open-label, 12-week study","volume":"7","author":"Ajgaonkar","year":"2026","journal-title":"Front Glob Womens Health"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.25122\/jml-2025-0147","article-title":"Efficacy and safety of Ashwagandha (Withania somnifera) root extract on stress and weight management in adults: a prospective, randomized, double-blind, placebo-controlled study","volume":"18","author":"Pakhale","year":"2025","journal-title":"J Med Life"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s11136-014-0785-6","article-title":"A methodological review of the short form health survey 36 (SF-36) and its derivatives among breast cancer survivors","volume":"24","author":"Treanor","year":"2015","journal-title":"Qual Life Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e30787","DOI":"10.7759\/cureus.30787","article-title":"Efficacy and safety of Ashwagandha (Withania somnifera) root extract for improvement of sexual health in healthy women: a prospective, randomized, placebo-controlled study","volume":"14","author":"Ajgaonkar","year":"2022","journal-title":"Cureus."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e7083","DOI":"10.7759\/cureus.7083","article-title":"Efficacy and tolerability of Ashwagandha root extract in the elderly for improvement of general well-being and sleep: a prospective, randomized, double-blind, placebo-controlled study","volume":"16","author":"Kelgane","year":"2020","journal-title":"Cureus"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e0257843","DOI":"10.1371\/journal.pone.0257843","article-title":"Effect of Ashwagandha (Withania somnifera) extract on sleep: a systematic review and meta-analysis","volume":"16","author":"Cheah","year":"2021","journal-title":"PLoS One"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e6466","DOI":"10.7759\/cureus.6466","article-title":"Adaptogenic and anxiolytic effects of Ashwagandha root extract in healthy adults: a double-blind, randomized, placebo-controlled clinical study","volume":"11","author":"Salve","year":"2019","journal-title":"Cureus."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"113276","DOI":"10.1016\/j.jep.2020.113276","article-title":"Clinical evaluation of the pharmacological impact of Ashwagandha root extract on sleep in healthy volunteers and insomnia patients: a double-blind, randomized, parallel-group, placebo-controlled study","volume":"264","author":"Langade","year":"2021","journal-title":"J Ethnopharmacol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ptr.70096","article-title":"Safety of 12-month administration of Ashwagandha (Withania somnifera) standardized root extract in healthy adults: a prospective, observational study","author":"Salve","year":"2025","journal-title":"Phytother Res"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e1556","DOI":"10.1002\/vms3.1556","article-title":"Effects of Ashwagandha (Withania somnifera) root extract on aging-related changes in healthy geriatric dogs: a randomized, double-blinded, placebo-controlled study","volume":"10","author":"Bharani","year":"2024","journal-title":"Vet Med Sci"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"13","DOI":"10.5214\/ans.0972.7531.200106","article-title":"Withania somnifera root extract extends lifespan of Caenorhabditis elegans","volume":"20","author":"Kumar","year":"2013","journal-title":"Ann Neurosci"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1823678\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:51:08Z","timestamp":1779339068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1823678\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":36,"alternative-id":["10.3389\/fnut.2026.1823678"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1823678","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"article-number":"1823678"}}