{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:50:48Z","timestamp":1789753848539,"version":"4.0.1"},"reference-count":78,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Standardised Ashwagandha root extract (SARE), characterised by its content of bioactive withanolides, is widely used for its antioxidant and adaptogenic properties; however, recent case reports have raised safety concerns, primarily involving non-standardised or multi-ingredient formulations. This systematic review evaluated the safety and tolerability of SARE in healthy adults, with a focus on clinical biomarkers and adverse event reporting. Methods: Randomised trials were identified through searches of PubMed, Web of Science and Google Scholar, published from 2010 to April 2026. Studies administering single-ingredient, standardised root-only extracts to generally healthy populations were included. Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Twenty-three studies with a total of 2317 participants met the inclusion criteria, with doses ranging from 125 to 600 mg\/day and intervention durations from a single dose to 180 days. Across studies, hepatic, renal, haematological, endocrine, and cardiovascular biomarkers remained within normal clinical ranges, with no clinically meaningful adverse alterations reported. Reductions in cortisol were consistently observed, while increases in testosterone remained within physiological ranges. No serious adverse events attributable to SARE were reported. Mild adverse events, including gastrointestinal discomfort, headache, and transient drowsiness, were infrequently reported and occurred in both intervention and comparator groups. Conclusions: SARE was well tolerated in healthy adults at the studied doses and durations. However, limited long-term data (&gt;180 days) and heterogeneity in study design and reporting warrant further large-scale, standardised trials to confirm safety across extended use and diverse populations. The review is registered in the PROSPERO database with ID CRD420261337116.<\/jats:p>","DOI":"10.3390\/ph19050725","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:06:21Z","timestamp":1777860381000},"page":"725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Back to the Roots: Safety and Tolerability of Standardised Ashwagandha (Withania somnifera) Root Extract in Healthy Adults\u2014A Systematic Review of Biomarkers and Adverse Events"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2811-925X","authenticated-orcid":false,"given":"Olivia C.","family":"Coope","sequence":"first","affiliation":[{"name":"Blanquerna School of Health Sciences, Ramon Llull University, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-8739","authenticated-orcid":false,"given":"Mark E. T.","family":"Willems","sequence":"additional","affiliation":[{"name":"School of Sport, Science and Engineering, University of Chichester, College Lane, Chichester PO19 6PE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Levington","sequence":"additional","affiliation":[{"name":"Strength and Nutrition Ltd., Brighton BN3 8PS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-3809","authenticated-orcid":false,"given":"Mark J.","family":"Tallon","sequence":"additional","affiliation":[{"name":"Legal Products Group Ltd., Ely CB7 4EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1804-2324","authenticated-orcid":false,"given":"Blanca","family":"Roman-Vi\u00f1as","sequence":"additional","affiliation":[{"name":"Department of Physical Activity and Sport Sciences, Psychology, Education and Sport Sciences, Blanquerna, Universitat Ramon Llull, 34 Cister, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2600-3512","authenticated-orcid":false,"given":"Tilly J.","family":"Spurr","sequence":"additional","affiliation":[{"name":"School of Sport, Science and Engineering, University of Chichester, College Lane, Chichester PO19 6PE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Djaoudene, O., Romano, A., Bradai, Y.D., Zebiri, F., Ouchene, A., Yousfi, Y., Amrane-Abider, M., Sahraoui-Remini, Y., and Madani, K. (2023). A Global Overview of Dietary Supplements: Regulation, Market Trends, Usage during the COVID-19 Pandemic, and Health Effects. Nutrients, 15.","DOI":"10.3390\/nu15153320"},{"key":"ref_2","unstructured":"Grand View Research (2025, March 29). Dietary Supplements Market Size and Share Report, 2030. Available online: https:\/\/www.grandviewresearch.com\/industry-analysis\/dietary-supplements-market-report."},{"key":"ref_3","first-page":"100592","article-title":"Common herbs for stress: The science and strategy of a botanical medicine approach to self-care","volume":"30","author":"Burns","year":"2023","journal-title":"J. Interprof. Educ. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Avigan, M.I., Mozersky, R.P., and Seeff, L.B. (2016). Scientific and Regulatory Perspectives in Herbal and Dietary Supplement Associated Hepatotoxicity in the United States. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030331"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"752","DOI":"10.21037\/hbsn-23-329","article-title":"Update on herbal and dietary supplement-induced liver injury: Current gaps and future directions","volume":"12","author":"Weber","year":"2023","journal-title":"HepatoBiliary Surg. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e63808","DOI":"10.2196\/63808","article-title":"Estimating Adverse Events Associated with Herbal Medicines Using Pharmacovigilance Databases: Systematic Review and Meta-Analysis","volume":"10","author":"Kongkaew","year":"2024","journal-title":"JMIR Public Health Surveill."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mikulska, P., Malinowska, M., Ignacyk, M., Szustowski, P., Nowak, J., Pesta, K., Szel\u0105g, M., Szklanny, D., Judasz, E., and Kaczmarek, G. (2023). Ashwagandha (Withania somnifera)\u2014Current Research on the Health-Promoting Activities: A Narrative Review. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041057"},{"key":"ref_8","first-page":"e55240","article-title":"Ayurvedic Herbal Medicines: A Literature Review of Their Applications in Female Reproductive Health","volume":"16","author":"Patibandla","year":"2024","journal-title":"Cureus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1177\/0300060517752022","article-title":"Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line","volume":"46","author":"Ahmed","year":"2018","journal-title":"J. Int. Med. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wici\u0144ski, M., Fajkiel-Madajczyk, A., S\u0142awatycki, J., Szambelan, M., Szyperski, P., Wojciechowski, P., W\u00f3jcicki, J., and Gawryjo\u0142ek, M. (2025). Ashwagandha (Withania somnifera) and Its Effects on Well-Being\u2014A Review. Nutrients, 17.","DOI":"10.3390\/nu17132143"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4964","DOI":"10.1007\/s12325-025-03292-7","article-title":"Superior Bioavailability of a Novel 1.5% Ashwagandha Formulation (ZenrootTM): A Randomized, Double-Blind, Single-Dose, Comparative, Oral Bioavailability Study in Healthy Adults","volume":"42","author":"Ramapalaniappan","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_12","first-page":"e96183","article-title":"Ashwagandha as an Adaptogenic Herb: A Comprehensive Review of Immunological and Neurological Effects","volume":"17","author":"Jamnekar","year":"2025","journal-title":"Cureus"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bonilla, D.A., Moreno, Y., Gho, C., Petro, J.L., Odriozola-Mart\u00ednez, A., and Kreider, R.B. (2021). Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis. J. Funct. Morphol. Kinesiol., 6.","DOI":"10.3390\/jfmk6010020"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.2174\/1570159X19666210712151556","article-title":"Effects of Withania somnifera (Ashwagandha) on stress and the stress-related neuropsychiatric disorders anxiety, depression, and insomnia","volume":"19","author":"Speers","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12986-025-00902-7","article-title":"Withania somnifera (Ashwagandha) supplementation: A review of its mechanisms, health benefits, and role in sports performance","volume":"22","author":"Sprengel","year":"2025","journal-title":"Nutr. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Salve, J., Kale, S., Prajapati, B.L., Sparavigna, A., Savant, M., Ademola, J., and Langade, D. (2025). Safety of 12-Months Administration of Ashwagandha (Withania somnifera) Standardized Root Extract in Healthy Adults: A Prospective, Observational Study. Phytother. Res.","DOI":"10.1002\/ptr.70096"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bokan, G., Glamo\u010danin, T., Mavija, Z., Vidovi\u0107, B., Stojanovi\u0107, A., Bj\u00f5rnsson, E., and Vu\u010di\u0107, V. (2023). Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. Pharmaceuticals, 16.","DOI":"10.3390\/ph16081129"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/liv.14393","article-title":"Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network","volume":"40","author":"Avula","year":"2020","journal-title":"Liver Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/19390211.2025.2514458","article-title":"Ashwagandha (Withania somnifera) Plant Extracts Affect the Cytochrome P450 System and Cytotoxicity of Primary Human Hepatocytes","volume":"22","author":"McDonald","year":"2025","journal-title":"J. Diet. Suppl."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ferreira, J.F., Ferreira, R.M., Maia, F., Fernandes, L.G., Le\u00e3o, C., and Pimenta, N. (2025). Biopsychological Effects of Ashwagandha (Withania somnifera) in Athletes and Healthy Individuals: An Overview of Reviews. Muscles, 4.","DOI":"10.3390\/muscles4030024"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s13668-023-00481-0","article-title":"Effects of Withania somnifera (Ashwagandha) on Hematological and Biochemical Markers, Hormonal Behavior, and Oxidant Response in Healthy Adults: A Systematic Review","volume":"12","author":"Afonso","year":"2023","journal-title":"Curr. Nutr. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1136\/emermed-2020-209567","article-title":"Population, Intervention, Comparison, Outcomes and Study (PICOS) Design as a Framework to Formulate Eligibility Criteria in Systematic Reviews","volume":"37","author":"Janati","year":"2020","journal-title":"Emerg. Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","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":"ref_25","doi-asserted-by":"crossref","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":"ref_26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4103\/0974-8520.169002","article-title":"Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults","volume":"36","author":"Choudhary","year":"2015","journal-title":"AYU (Int. Q. J. Res. Ayurveda)"},{"key":"ref_27","first-page":"e6466","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":"ref_28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.18203\/2319-2003.ijbcp20214831","article-title":"A comparative pharmacokinetics study of Ashwagandha (Withania somnifera) Root Extract sustained-release capsules: An open-label, randomized, two treatment, two-sequence, two period, single-dose crossover clinical study","volume":"11","author":"Alluri","year":"2021","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8254344","DOI":"10.1155\/2021\/8254344","article-title":"Efficacy and Safety of Ashwagandha Root Extract on Cognitive Functions in Healthy, Stressed Adults: A Randomized, Double-Blind, Placebo-Controlled Study","volume":"2021","author":"Gopukumar","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","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":"ref_31","doi-asserted-by":"crossref","first-page":"113929","DOI":"10.1016\/j.jep.2021.113929","article-title":"A double-blind, randomized, placebo-controlled trial on the effect of Ashwagandha (Withania somnifera Dunal.) root extract in improving cardiorespiratory endurance and recovery in healthy athletic adults","volume":"272","author":"Tiwari","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","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":"ref_33","doi-asserted-by":"crossref","first-page":"e741","DOI":"10.1002\/hsr2.741","article-title":"Effect of standardized root extract of ashwagandha (Withania somnifera) on well-being and sexual performance in adult males: A randomized controlled trial","volume":"5","author":"Chauhan","year":"2022","journal-title":"Health Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e71388","DOI":"10.1002\/fsn3.71388","article-title":"Safety and Tolerability of Withania somnifera Root Extract in Healthy Male Participants: A Pilot Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"14","author":"Vaidya","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Naik, K.S., Muralidhar, G., Rao, B.S., and Wankhade, K. (2024). An 8-Week Oral Therapy with Ashwagandha (Withania somnifera) Root Extract (600 mg\/day) Improves Frailty and Quality of Life in Elderly: A Prospective, Randomized, Placebo-Controlled, Efficacy and Safety Study. medRxiv.","DOI":"10.1101\/2024.10.15.24315515"},{"key":"ref_36","first-page":"e68940","article-title":"Evaluation of Withania somnifera (L.) Dunal (Ashwagandha) on Physical Performance, Biomarkers of Inflammation, and Muscle Status in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Study","volume":"16","author":"Raut","year":"2024","journal-title":"Cureus"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"335","DOI":"10.12688\/f1000research.130932.2","article-title":"Effects of Ashwagandha (Withania somnifera) standardized root extract on physical endurance and VO2max in healthy adults performing resistance training: An eight-week, prospective, randomized, double-blind, placebo-controlled study","volume":"12","author":"Verma","year":"2024","journal-title":"F1000Research"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1007\/s12325-025-03327-z","article-title":"A New Ashwagandha Formulation (ZenrootTM) Alleviates Stress and Anxiety Symptoms While Improving Mood and Sleep Quality: A Randomized, Double-Blind, Placebo-Controlled Clinical Study","volume":"42","author":"Mahadevan","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101155","DOI":"10.1016\/j.jaim.2025.101155","article-title":"Efficacy and safety of eight-week therapy with Ashwagandha root extract in improvement of sexual health in healthy men: Findings of a prospective, randomized, double-blind, placebo-controlled study","volume":"16","author":"Mutha","year":"2025","journal-title":"J. Ayurveda Integr. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2459467","DOI":"10.1080\/23311908.2025.2459467","article-title":"Efficacy and safety of ashwagandha root extract on sexual health in healthy women: Findings of a prospective, randomized, double-blind, placebo-controlled study","volume":"12","author":"Mutha","year":"2025","journal-title":"Cogent Psychol."},{"key":"ref_41","first-page":"88","article-title":"Efficacy of Ashwagandha Extract Formulation (ASVAMAN\u00ae) on Improvement of Energy and Endurance: A Randomized, Double-blind, Placebo-controlled Clinical Study in Healthy Adults","volume":"7","author":"Puttaswamy","year":"2025","journal-title":"Eur. J. Med. Health Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5114\/biolsport.2025.147453","article-title":"Effects of an 8-week high intensity interval training (HIIT) and ashwagandha supplementation on aerobic capacity, muscle oxygenation and haematological parameters in healthy men","volume":"42","author":"Klusiewicz","year":"2025","journal-title":"Biol. Sport"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Coope, O.C., Otaegui, E., Su\u00e1rez, M., Levington, A., Abad-Sangr\u00e0, M., Lloyd, B., Spurr, T.J., and Roman-Vi\u00f1as, B. (2026). Ashwagandha Root Extract Stabilises Physiological Stress Responses in Male and Female Team Sports Athletes During Pre-Season Training. Nutrients, 18.","DOI":"10.3390\/nu18020230"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Vani, I., Muralidhar, G., and Rao, B.S. (2026). A prospective, randomized, double-blind, placebo-controlled study on efficacy and safety of Ashwagandha root extract (Withania somnifera) for managing menopausal symptoms in women. Front. Reprod. Health, 7.","DOI":"10.3389\/frph.2025.1647721"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ferreira, J.F., Maia, F., Ferreira, R.M., Martinho, D.V., Fernandes, L.G., Le\u00e3o, C., and Pimenta, N. (2026). Effects of 8 days of Ashwagandha supplementation on strength, fatigue, soreness, and recovery in amateur handball players: A double-blind, randomized, placebo-controlled trial. Nutr. Health, Available online: https:\/\/journals.sagepub.com\/doi\/10.1177\/02601060261439102.","DOI":"10.1177\/02601060261439102"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pakhale, K., Salve, J., Ademola, J., Parraca, J., and Langade, D. (2026). Safety of 8-Week Administration with Ashwagandha (Withania somnifera) Root Extract in Adults with Stress and Anxiety: Findings from a Prospective, Randomized, Multi-Center, Double-Blinded, Placebo-Controlled Study. Phytother. Res., 1\u201311.","DOI":"10.1002\/ptr.70315"},{"key":"ref_47","first-page":"662","article-title":"The Meanings of Health and its Promotion","volume":"47","author":"Sartorius","year":"2006","journal-title":"Croat. Med. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_49","doi-asserted-by":"crossref","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":"ref_50","doi-asserted-by":"crossref","first-page":"e17186","DOI":"10.1097\/MD.0000000000017186","article-title":"An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study","volume":"98","author":"Lopresti","year":"2019","journal-title":"Medicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"250","DOI":"10.4103\/ijem.ijem_337_23","article-title":"A Comparison of 06:00 a.m. Versus 09:00 a.m. Serum Cortisol as a Basal Morning Cortisol in Guwahati, Assam: A Pilot Study","volume":"28","author":"Saikia","year":"2024","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3390\/ph3010188","article-title":"Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress\u2014Protective Activity","volume":"3","author":"Panossian","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1007\/s11064-009-9987-7","article-title":"Neuroprotective Effects of Withania somnifera Dunal.: A Possible Mechanism","volume":"34","author":"Bhatnagar","year":"2009","journal-title":"Neurochem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"112175","DOI":"10.1016\/j.biopha.2021.112175","article-title":"Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects","volume":"143","author":"Paul","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_55","first-page":"e23494","article-title":"Ashwagandha as a Unique Cause of Thyrotoxicosis Presenting with Supraventricular Tachycardia","volume":"14","author":"Kamal","year":"2022","journal-title":"Cureus"},{"key":"ref_56","first-page":"e55352","article-title":"Painless Thyroiditis by Withania somnifera (Ashwagandha)","volume":"16","author":"Hayashi","year":"2024","journal-title":"Cureus"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Jasi\u0144ska-Balwierz, A., Krypel, P., \u015awis\u0142owski, P., Rajfur, M., Balwierz, R., and Och\u0119dzan-Siod\u0142ak, W. (2025). Heavy Metal Contamination in Adaptogenic Herbal Dietary Supplements: Experimental, Assessment and Regulatory Safety Perspectives. Biology, 14.","DOI":"10.3390\/biology14111479"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e18962","DOI":"10.7717\/peerj.18962","article-title":"Association between toxic heavy metals and noncancerous thyroid disease: A scoping review","volume":"13","year":"2025","journal-title":"PeerJ"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1055\/s-0031-1300432","article-title":"Placebo\u2014Efficacy and Adverse Effects in Controlled Clinical Trials","volume":"49","author":"Weihrauch","year":"2011","journal-title":"Arzneimittelforschung"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Toews, I., Anglemyer, A., Nyirenda, J.L.Z., Alsaid, D., Balduzzi, S., Grummich, K., Schwingshackl, L., and Bero, L. (2024). Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials: A meta-epidemiological study. Cochrane Libr., 2024.","DOI":"10.1002\/14651858.MR000034.pub3"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00204-015-1521-x","article-title":"Hepatotoxicity of green tea: An update","volume":"89","author":"Mazzanti","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/hep.28813","article-title":"Liver injury from herbal and dietary supplements","volume":"65","author":"Navarro","year":"2016","journal-title":"Hepatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.2165\/11317010-000000000-00000","article-title":"Interactions Between Herbal Medicines and Prescribed Drugs","volume":"69","author":"Izzo","year":"2009","journal-title":"Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1592\/phco.31.5.490","article-title":"Is There a Risk of Bleeding Associated with StandardizedGinkgo bilobaExtract Therapy? A Systematic Review and Meta-analysis","volume":"31","author":"Kellermann","year":"2011","journal-title":"Pharmacotherapy"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wang, H., Chen, Y., Wang, L., Liu, Q., Yang, S., and Wang, C.-Q. (2023). Advancing herbal medicine: Enhancing product quality and safety through robust quality control practices. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1265178"},{"key":"ref_66","unstructured":"Heads of Food Safety Agencies (2026, March 28). First Report of the HoA Working Group \u201cFood Supplements.\u201d Bund.de. Available online: https:\/\/www.bvl.bund.de\/SharedDocs\/Downloads\/01_Lebensmittel\/Internationales\/Report_HoA_WG_FS-de.pdf."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Brendler, T., Al-Mondhiry, R., Lang, L., Marles, R., Tallon, M., and Raghu, A. (2025). Ashwagandha: Is It Safe? Part 1: A Regulatory Review. Phytother. Res., Available online: https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70151.","DOI":"10.1002\/ptr.70151"},{"key":"ref_68","unstructured":"Committee on Toxicity of Chemicals in Food, and Consumer Products and the Environment (COT) (2026, March 29). Potential Future Discussion Items\u2014Horizon Scanning, Available online: https:\/\/cot.food.gov.uk\/sites\/default\/files\/2026-01\/TOX-2026-%2004%20horizon%20scanning.pdf."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Williamson, E.M., and Brendler, T. (2025). Ashwagandha: Is It Safe? Part 2: A Preclinical Evidence Review. Phytother. Res.","DOI":"10.1002\/ptr.70090"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Brendler, T. (2025). Is Ashwagandha an Abortifacient?. Phytother. Res., Available online: https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70150.","DOI":"10.1002\/ptr.70150"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Tallon, M.J., Koturbash, I., and Blum, J.L. (2025). A Systematic and Ethnobotanical Review of Ashwagandha\u2019s (Withania somnifera) Teratogenic and Abortifacient Potentials. Phytother. Res., Available online: https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70079.","DOI":"10.1002\/ptr.70079"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Casiano-Manzano, S., Torres-Larrubia, M., Masa-Caballero, A., Jim\u00e9nez-Colmenarez, Z., Mart\u00edn-Noguerol, E., Fern\u00e1ndez-Bermejo, M., and Sol\u00eds-Mu\u00f1oz, P. (2023). Changing perspectives: Unveiling the risks of ashwagandha-induced hepatotoxicity. Rev. Esp. Enfermedades Dig.","DOI":"10.17235\/reed.2023.10080\/2023"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e37903","DOI":"10.1097\/MD.0000000000037903","article-title":"A comprehensive review on the hepatotoxicity of herbs used in the Indian (Ayush) systems of alternative medicine","volume":"103","author":"Philips","year":"2024","journal-title":"Medicine"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kumar, A., Sah, B.K., Ahmad, F., Jamwal, V., and Sahu, S.K. (2026). Potential Adverse Effects of Ashwagandha: A Critical Review of Preclinical and Clinical Evidence. Phytother. Res., Available online: https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70158.","DOI":"10.1002\/ptr.70158"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1111\/bcp.16371","article-title":"Establishing reference ranges for circulating biomarkers of drug-induced liver injury in healthy human volunteers","volume":"91","author":"Jorgensen","year":"2025","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","article-title":"Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100024","DOI":"10.1016\/j.dmd.2024.100024","article-title":"Evaluation of reversible cytochrome P450 inhibition by Withania somnifera leaf and root extracts","volume":"53","author":"Raichura","year":"2024","journal-title":"Drug Metab. Dispos."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3109\/01480545.2014.900073","article-title":"Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats","volume":"38","author":"Prabu","year":"2014","journal-title":"Drug Chem. Toxicol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/725\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:03:19Z","timestamp":1781157799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,2]]},"references-count":78,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ph19050725"],"URL":"https:\/\/doi.org\/10.3390\/ph19050725","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,2]]}}}