{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:01:15Z","timestamp":1790226075816,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T00:00:00Z","timestamp":1567036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"gnosis","award":["8810\/02112017"],"award-info":[{"award-number":["8810\/02112017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Osteoarthritis (OA) is the most common form of arthritis in the world and is characterized by pain, various disabilities and loss of quality of life. Chondroitin sulfate (CS) is recommended as first-line therapy. CS of non-animal origin is of great interest for safety and sustainability reasons. This study aims to investigate the anti-inflammatory effects, anti-pain and ability-enhancement of a short-term supplementation with non-animal CS in overweight subjects with OA. In a randomized, double-blind, placebo-controlled pilot study, 60 overweight adults with symptomatic OA were allocated to consume 600 mg of non-animal CS (n = 30) or a placebo (n = 30) daily for 12 consecutive weeks. The assessment of knee-pain, quality of life, related inflammation markers and body composition was performed at 0, 4 and 12 weeks. The Tegner Lysholm Knee Scoring (TLKS) scale of the experimental group showed a statistically significant increase (+10.64 points; confidence interval (95% confidence interval (CI) 5.57; 15.70; p &lt; 0.01), while the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score decreased (\u221212.24 points; CI 95% \u221216.01; \u22128.38; p &lt; 0.01). The results also showed a decrease in the C-reactive protein (CRP) level (\u22120.14 mg\/dL, CI 95% \u22120.26; \u22120.04; p &lt; 0.01) and erythrocyte sedimentation rate (ESR) level (\u22125.01 mm\/h, CI 95% \u22129.18; \u22120.84, p &lt; 0.01) as well as the visual analogue scale (VAS) score in both knees. In conclusion, this pilot study demonstrates the effectiveness of non-animal CS supplementation in overweight subjects with knee OA in improving knee function, pain and inflammation markers.<\/jats:p>","DOI":"10.3390\/nu11092027","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T11:26:22Z","timestamp":1567077982000},"page":"2027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effectiveness of Non-Animal Chondroitin Sulfate Supplementation in the Treatment of Moderate Knee Osteoarthritis in a Group of Overweight Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8336-4851","authenticated-orcid":false,"given":"Mariangela","family":"Rondanelli","sequence":"first","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Braschi","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizialla Persona \u2018\u2018Istituto Santa Margherita\u2019\u2019, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1088-6648","authenticated-orcid":false,"given":"Clara","family":"Gasparri","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizialla Persona \u2018\u2018Istituto Santa Margherita\u2019\u2019, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Nichetti","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizialla Persona \u2018\u2018Istituto Santa Margherita\u2019\u2019, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Anna","family":"Faliva","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizialla Persona \u2018\u2018Istituto Santa Margherita\u2019\u2019, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-1787","authenticated-orcid":false,"given":"Gabriella","family":"Peroni","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizialla Persona \u2018\u2018Istituto Santa Margherita\u2019\u2019, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7693-4542","authenticated-orcid":false,"given":"Maurizio","family":"Naso","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizialla Persona \u2018\u2018Istituto Santa Margherita\u2019\u2019, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Iannello","sequence":"additional","affiliation":[{"name":"General Management, Azienda di Servizialla Persona Istituto Santa Margherita, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6413-9253","authenticated-orcid":false,"given":"Daniele","family":"Spadaccini","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizialla Persona \u2018\u2018Istituto Santa Margherita\u2019\u2019, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f2","family":"Miraglia","sequence":"additional","affiliation":[{"name":"Clinical &amp; Pre-clinical Development, Gnosis SpA, 20121 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Putignano","sequence":"additional","affiliation":[{"name":"SP Diabetic Outpatient Clinic, ASST Monza, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2720-1473","authenticated-orcid":false,"given":"Tariq A.","family":"Alalwan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Bahrain, Sakhir Campus P. O. Box 32038, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Perna","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Bahrain, Sakhir Campus P. O. Box 32038, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","first-page":"131","article-title":"Appropriateness of clinical and organizational criteria for intra-articular injectiontherapies in osteoarthritis. A Delphi method consensus initiative among experts in Italy","volume":"51","author":"Paoloni","year":"2015","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_3","first-page":"169","article-title":"Epidemiology and risk factors in osteoarthritis: Literature review data from \u201cOASIS\u201d study","volume":"56","author":"Gulli","year":"2011","journal-title":"Reumatismo"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.joca.2014.11.019","article-title":"Current evidence on risk factors for knee osteoarthritis in older adults: A systematic review and meta-analysis","volume":"23","author":"Silverwood","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Grotle, M., Hagen, K.B., Natvig, B., Dahl, F.A., and Kvien, T.K. (2008). Obesity and osteoarthritis in knee, hip and\/or hand: An epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet. Disord., 9.","DOI":"10.1186\/1471-2474-9-132"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.joca.2009.08.010","article-title":"Risk factors for onset of osteoarthritis of the knee in older adults: A systematic review and meta-analysis","volume":"18","author":"Blagojevic","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.maturitas.2016.04.006","article-title":"Obesity and osteoarthritis","volume":"89","author":"Kulkarni","year":"2016","journal-title":"Maturitas"},{"key":"ref_8","first-page":"201","article-title":"Obesity As a Risk Factor for Osteoarthritis: Mechanical Versus Metabolic","volume":"87","author":"Eaton","year":"2004","journal-title":"Med. Health R. I."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"586","DOI":"10.2174\/138945010791011857","article-title":"Obesity and inflammation\u2014Targets for OA therapy","volume":"11","author":"Iannone","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1016\/j.semarthrit.2017.07.002","article-title":"International endorsement of the ESCEO algorithm for management of knee osteoarthritis in clinical practice","volume":"47","author":"Cooper","year":"2017","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1136\/ard.2003.011742","article-title":"EULAR Recommendations 2003: An evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT)","volume":"62","author":"Jordan","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.joca.2014.01.003","article-title":"OARSI guidelines for the non-surgical management of knee osteoarthritis","volume":"22","author":"McAlindon","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.maturitas.2014.04.015","article-title":"What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis?","volume":"78","author":"Henrotin","year":"2014","journal-title":"Maturitas"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.joca.2010.02.017","article-title":"Modulation of inflammation by chondroitin sulfate","volume":"18","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1111\/j.1582-4934.2009.00826.x","article-title":"Immunomodulatory and anti-inflammatory effects of chondroitin sulphate","volume":"13","author":"Montell","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","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":"ref_17","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.atherosclerosis.2015.12.016","article-title":"Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity","volume":"245","author":"Rosas","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Stabler, T.V., Montell, E., Verg\u00e9s, J., Huebner, J.L., and Kraus, V.B. (2017). Chondroitin Sulfate Inhibits Monocyte Chemoattractant Protein-1 Release From 3T3-L1 Adipocytes: A New Treatment Opportunity for Obesity-Related Inflammation?. Biomark. Insights, 12.","DOI":"10.1177\/1177271917726964"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/ard.2008.106930","article-title":"Association between weight or body mass index and hand osteoarthritis: A systematic review","volume":"69","author":"Yusuf","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000366285","article-title":"Effect of nonanimal high- and low-molecular-mass chondroitin sulfates produced by a biotechnological process in an animal model of polyarthritis","volume":"94","author":"Ponist","year":"2014","journal-title":"Pharmacology"},{"key":"ref_21","first-page":"CD005614","article-title":"Chondroitin for osteoarthritis","volume":"1","author":"Singh","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.fct.2016.04.013","article-title":"Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability","volume":"93","author":"Miraglia","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.carbpol.2012.06.009","article-title":"Residual keratan sulfate in chondroitin sulfate formulations for oral administration","volume":"90","author":"Pomin","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ab.2013.11.028","article-title":"Selective removal of keratan sulfate in chondroitin sulfate samples by sequential precipitation with ethanol","volume":"448","author":"Galeotti","year":"2014","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1007\/s00253-010-2677-1","article-title":"Production of chondroitin sulfate and chondroitin","volume":"87","author":"Schiraldi","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/cpdd.587","article-title":"Oral Bioavailability and Pharmacokinetics of Nonanimal Chondroitin Sulfate and Its Constituents in Healthy Male Volunteers","volume":"8","author":"Volpi","year":"2018","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_27","first-page":"1833","article-title":"Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee","volume":"15","author":"Bellamy","year":"1988","journal-title":"J. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1177\/036354658201000306","article-title":"Evaluation of knee ligament surgery results with special emphasis on use of a scoring scale","volume":"10","author":"Lysholm","year":"1982","journal-title":"Am. J. Sports Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/nur.4770130405","article-title":"A critical review of visual analogue scales in the measurement of clinical phenomena","volume":"13","author":"Wewers","year":"1990","journal-title":"Res. Nurs. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/00005650-199303000-00006","article-title":"The MOS 36-item short-form health survey (Sf-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs","volume":"31","author":"McHorney","year":"1993","journal-title":"Med. Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/oxfordjournals.aje.a009520","article-title":"Epidemiology of Sarcopenia among the Elderly in New Mexico","volume":"147","author":"Baumgartner","year":"1998","journal-title":"Am. J. Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1038\/nutd.2016.38","article-title":"Validity of visceral adiposity estimates from DXA against MRI in Kuwaiti men and women","volume":"7","author":"Mohammad","year":"2017","journal-title":"Nutr. Diabetes"},{"key":"ref_33","first-page":"523","article-title":"A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee","volume":"30","author":"Cohen","year":"2003","journal-title":"J. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s12325-019-00921-w","article-title":"Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials","volume":"36","author":"Honvo","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1211\/jpp.61.10.0002","article-title":"Quality of different chondroitin sulfate preparations in relation to their therapeutic activity","volume":"61","author":"Volpi","year":"2009","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.semarthrit.2015.11.010","article-title":"A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting","volume":"45","author":"Cooper","year":"2016","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1177\/0004563215610142","article-title":"Elevated erythrocyte sedimentation rate and high-sensitivity C-reactive protein in osteoarthritis of the knee: Relationship with clinical findings and radiographic severity","volume":"53","author":"Hanada","year":"2016","journal-title":"Ann. Clin. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1136\/annrheumdis-2013-204494","article-title":"Circulating C reactive protein in osteoarthritis: A systematic review and meta-analysis","volume":"74","author":"Jin","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.joca.2008.06.008","article-title":"Anti-inflammatory activity of chondroitin sulfate","volume":"16","author":"Iovu","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.diabres.2004.11.007","article-title":"Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-\u03b1 and IL-6","volume":"69","author":"Park","year":"2005","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1136\/annrheumdis-2014-206792","article-title":"Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: A multicentre, randomised, double-blind, non-inferiority trial versus celecoxib","volume":"75","author":"Hochberg","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa052771","article-title":"Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis","volume":"354","author":"Clegg","year":"2006","journal-title":"N. Engl. J. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/9\/2027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:14:59Z","timestamp":1760188499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/9\/2027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,29]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["nu11092027"],"URL":"https:\/\/doi.org\/10.3390\/nu11092027","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,29]]}}}