{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:31:56Z","timestamp":1786422716955,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"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<\/jats:title>\n                    <jats:p>Knee osteoarthritis (OA) is a common cause of pain and disability without a cure. Glucosamine is widely used as a symptomatic treatment owing to its safety, yet its clinical efficacy remains uncertain amid mixed trial results and conflicting guidelines. This umbrella review synthesized evidence from published systematic reviews and meta-analyses on the effectiveness and safety of glucosamine in knee OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We searched MEDLINE (via PubMed), Embase, Web of Science, and the Cochrane Library up to November 2025. Eligible studies were systematic reviews or meta-analyses of randomized trials in adults with knee OA comparing glucosamine (any formulation) with placebo or other non-surgical comparators and reporting pain, physical function, or joint structure. Two reviewers independently screened, extracted data, and assessed quality (AMSTAR-2). Key outcomes were pain (visual analog scale [VAS] and WOMAC [Western Ontario and McMaster Universities Osteoarthritis Index]), functional measures, joint space narrowing (JSN), and adverse events. Overlap among shared primary trials was quantified using the corrected covered area, and the resulting dependence was addressed using robust variance estimation to pool standardized mean differences (SMDs), with\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05 considered significant. Effect sizes were interpreted against minimal clinically important difference (MCID) thresholds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nineteen reviews were included (most low or critically low quality). Glucosamine produced a small but statistically significant reduction in VAS pain (SMD\u202f\u2212\u202f0.36,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.02), whereas WOMAC pain showed no significant difference. Functional outcomes (WOMAC total and function) showed no significant improvement. Glucosamine was associated with significant slowing of JSN progression (SMD\u202f\u2212\u202f0.32,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.01), though this signal derived mainly from long-duration sulfate trials. The magnitude of the significant effects was at or below accepted MCID thresholds. Adverse event rates did not differ from placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Glucosamine demonstrated at most minimal-to-modest efficacy for knee OA, yielding a small pain reduction and possible slowing of radiographic progression but no clear functional benefit, with effects at or below the threshold of clinical importance. Given the low quality of evidence, extensive overlap among reviews, and the predominantly out-of-pocket nature of glucosamine use, these findings should be interpreted with caution and weighed against cost in shared decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier (CRD420251207513).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1806413","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:20:51Z","timestamp":1786422051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucosamine for knee osteoarthritis: an umbrella review"],"prefix":"10.3389","volume":"13","author":[{"given":"Yanfei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center","place":["Baton Rouge, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Shen","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center","place":["Baton Rouge, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Hu","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center","place":["Baton Rouge, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengdi","family":"Lu","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center","place":["Baton Rouge, LA, United States"]},{"name":"Department of Orthopaedics, Shanghai Sixth People\u2019s Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/BF03327356","article-title":"Epidemiology of osteoarthritis: prevalence, risk factors and functional impact","volume":"15","author":"Corti","year":"2003","journal-title":"Aging Clin Exp Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/S0140-6736(12)61729-2","article-title":"Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990\u20132010: a systematic analysis for the global burden of disease study 2010","volume":"380","author":"Vos","year":"2012","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1136\/annrheumdis-2013-204763","article-title":"The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study","volume":"73","author":"Cross","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/1759720X20975927","article-title":"Glucosamine sulphate: an umbrella review of health outcomes","volume":"12","author":"Veronese","year":"2020","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"7444","DOI":"10.3390\/jcm13237444","article-title":"Comparative efficacy of glucosamine-based combination therapies in alleviating knee osteoarthritis pain: a systematic review and network meta-analysis","volume":"13","author":"Sumsuzzman","year":"2024","journal-title":"J Clin Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3390\/pharmacy11040117","article-title":"Effectiveness and safety of glucosamine in osteoarthritis: a systematic review","volume":"11","author":"Vo","year":"2023","journal-title":"Pharmacy (Basel)"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"c4675","DOI":"10.1136\/bmj.c4675","article-title":"Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis","volume":"341","author":"Wandel","year":"2010","journal-title":"BMJ"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0140-6736(00)03610-2","article-title":"Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial","volume":"357","author":"Reginster","year":"2001","journal-title":"Lancet"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.rdc.2022.03.009","article-title":"Osteoarthritis treatment guidelines from six professional societies: similarities and differences","volume":"48","author":"Overton","year":"2022","journal-title":"Rheum Dis Clin N Am"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/acr.21596","article-title":"American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee","volume":"64","author":"Hochberg","year":"2012","journal-title":"Arthritis Care Res (Hoboken)."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/art.41142","article-title":"2019 American College of Rheumatology\/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee","volume":"72","author":"Kolasinski","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthr Cartil"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.semarthrit.2019.04.008","article-title":"An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO)","volume":"49","author":"Bruy\u00e8re","year":"2019","journal-title":"Semin Arthritis Rheum"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1097\/XEB.0000000000000055","article-title":"Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach","volume":"13","author":"Aromataris","year":"2015","journal-title":"Int J Evid Based Healthc"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"10","author":"Page","year":"2020","journal-title":"Syst Rev"},{"key":"ref16","volume-title":"Cochrane Handbook for systematic Reviews of Interventions Cochrane Handbook for systematic Reviews of Interventions","author":"Julian","year":"2023"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.jclinepi.2013.11.007","article-title":"Systematic review finds overlapping reviews were not mentioned in every other overview","volume":"67","author":"Pieper","year":"2014","journal-title":"J Clin Epidemiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/jrsm.5","article-title":"Robust variance estimation in meta-regression with dependent effect size estimates","volume":"1","author":"Hedges","year":"2010","journal-title":"Res Synth Methods"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1037\/met0000011","article-title":"Small sample adjustments for robust variance estimation with meta-regression","volume":"20","author":"Tipton","year":"2015","journal-title":"Psychol Methods"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1136\/ard.2004.022905","article-title":"Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement","volume":"64","author":"Tubach","year":"2005","journal-title":"Ann Rheum Dis"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1136\/ard.2004.023028","article-title":"Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state","volume":"64","author":"Tubach","year":"2005","journal-title":"Ann Rheum Dis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1002\/1529-0131(200108)45:4<384::AID-ART352>3.0.CO;2-0","article-title":"Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities","volume":"45","author":"Angst","year":"2001","journal-title":"Arthritis Rheum"},{"key":"ref23","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen","year":"1988"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"j4008","DOI":"10.1136\/bmj.j4008","article-title":"AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both","volume":"358","author":"Shea","year":"2017","journal-title":"BMJ"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1136\/bjsports-2016-097333","article-title":"Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis","volume":"52","author":"Liu","year":"2018","journal-title":"Br J Sports Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1007\/s00296-018-4077-2","article-title":"Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials","volume":"38","author":"Simental-Mend\u00eda","year":"2018","journal-title":"Rheumatol Int"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s00296-009-0969-5","article-title":"Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis","volume":"30","author":"Lee","year":"2010","journal-title":"Rheumatol Int"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s13018-018-0871-5","article-title":"Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials","volume":"13","author":"Zhu","year":"2018","journal-title":"J Orthop Surg Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"331","DOI":"10.3390\/medicina61020331","article-title":"Effectiveness and safety of SYSADOAs used in eastern and Western regions for the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials\u2014SYSADOAs are effective and safe for knee OA","volume":"61","author":"Park","year":"2025","journal-title":"Medicina"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1007\/s10067-018-4106-2","article-title":"Effects of glucosamine in patients with osteoarthritis of the knee: a systematic review and meta-analysis","volume":"37","author":"Ogata","year":"2018","journal-title":"Clin Rheumatol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/ijcp.12115","article-title":"Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomized, double-blind, placebo-controlled trials","volume":"67","author":"Wu","year":"2013","journal-title":"Int J Clin Pract"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1007\/s10787-024-01460-9","article-title":"Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis","volume":"32","author":"Rabade","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1136\/annrheumdis-2017-211149","article-title":"Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trial bank","volume":"76","author":"Runhaar","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1002\/acr.22376","article-title":"Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials","volume":"66","author":"Eriksen","year":"2014","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"2564","DOI":"10.1001\/jama.2018.19319","article-title":"Association of pharmacological treatments with long-term pain control in patients with knee osteoarthritis: a systematic review and meta-analysis","volume":"320","author":"Gregori","year":"2018","journal-title":"JAMA"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s40266-019-00662-z","article-title":"Safety of symptomatic slow-acting drugs for osteoarthritis: outcomes of a systematic review and meta-analysis","volume":"36","author":"Honvo","year":"2019","journal-title":"Drugs Aging"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1001\/archinte.163.13.1514","article-title":"Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis","volume":"163","author":"Richy","year":"2003","journal-title":"Arch Intern Med"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1177\/0363546514533777","article-title":"Chondroprotection and the prevention of osteoarthritis progression of the knee: a systematic review of treatment agents","volume":"43","author":"Gallagher","year":"2015","journal-title":"Am J Sports Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.joca.2011.01.007","article-title":"The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature","volume":"19","author":"Dostrovsky","year":"2011","journal-title":"Osteoarthr Cartil"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta13520","article-title":"The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation","volume":"13","author":"Black","year":"2009","journal-title":"Health Technol Assess"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s12891-019-2525-0","article-title":"Osteoarthritis: a systematic review of long-term safety implications for knee osteoarthritis","volume":"20","author":"Charlesworth","year":"2019","journal-title":"BMC Musculoskelet Disord"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e25S402","DOI":"10.54448\/ijn25S402","article-title":"Major clinical outcomes and nutraceutical treatments of knee osteoarthritis: a systematic review","volume":"18","author":"Morais","year":"2025","journal-title":"Int J Nutrol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1185\/03007995.2016.1154521","article-title":"A review of glucosamine for knee osteoarthritis: why patented crystalline glucosamine sulfate should be differentiated from other glucosamines to maximize clinical outcomes","volume":"32","author":"Kucharz","year":"2016","journal-title":"Curr Med Res Opin"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.joca.2020.10.004","article-title":"Visual analogue scale has higher assay sensitivity than WOMAC pain in detecting between-group differences in treatment effects: a meta-epidemiological study","volume":"29","author":"da Costa","year":"2021","journal-title":"Osteoarthr Cartil"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1007\/s00296-018-4077-2","article-title":"Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis","volume":"38","author":"Simental-Mend\u00eda","year":"2018","journal-title":"Rheumatol Int"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1001\/archinte.162.18.2113","article-title":"Glucosamine sulphate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled study","volume":"162","author":"Pavelk\u00e1","year":"2002","journal-title":"Arch Intern Med"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/1471-2474-9-116","article-title":"The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature","volume":"9","author":"Bedson","year":"2008","journal-title":"BMC Musculoskelet Disord"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.joca.2007.06.011","article-title":"Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials","volume":"16","author":"Bruy\u00e8re","year":"2008","journal-title":"Osteoarthr Cartil"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1806413\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:20:53Z","timestamp":1786422053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1806413\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":48,"alternative-id":["10.3389\/fnut.2026.1806413"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1806413","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"article-number":"1806413"}}