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This 12-week, randomized, double-blind, placebo-controlled pilot study investigated the efficacy of a formulation containing collagen type II, glucosamine hydrochloride and chondroitin sulfate, in alleviating knee OA symptoms in subjects with mild to moderate knee pain. Fifty-four participants were enrolled, with 52 completing the study. Participants were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), performance-based physical function tests and global assessment tests. Results indicated significant improvements in the verum group compared to placebo. KOOS subscales showed improvements in symptoms (8.16%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), sport\/recreation (25.25%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), and quality of life (27.66%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Stiffness improved by 14.68% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) in the verum group. Both groups exhibited significant pain reduction (KOOS pain,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01 for verum and placebo, respectively). Performance-based measures, such as the Chair Stand test, improved significantly in both groups, though other metrics showed no significant differences. The verum group exhibited a linear improvement over 12 weeks, contrasting with the placebo group\u2019s initial response and subsequent plateau. SF-36 Physical Component scores improved in both groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), but mental health scores remained unchanged. Global assessment favoured the verum group, with more participants reporting OA improvement and recommending the product (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Biomarkers hsCRP and COMP showed no significant changes, likely due to sample variability. While the study did not achieve its primary endpoint, the nutritional formulation demonstrated an excellent safety profile and encouraging improvements in patient-reported symptoms and quality of life, warranting larger confirmatory trials.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Registration number:<\/jats:bold>\n                    DRKS00029563 05\/10\/2022\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-11723-2","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T17:46:05Z","timestamp":1752601565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of cartilage-supporting nutritional supplementation on knee osteoarthritis symptoms and quality of life in a 12-week randomized double-blind placebo-controlled pilot study"],"prefix":"10.1038","volume":"15","author":[{"given":"Johannes-Paul","family":"Fladerer-Grollitsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Kompek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Menzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Sch\u00f6n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"11723_CR1","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1016\/j.joca.2015.03.036","volume":"23","author":"VB Kraus","year":"2015","unstructured":"Kraus, V. B., Blanco, F. J., Englund, M., Karsdal, M. A. & Lohmander, L. S. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthr. Cartil. 23, 1233\u20131241. https:\/\/doi.org\/10.1016\/j.joca.2015.03.036 (2015).","journal-title":"Osteoarthr. Cartil."},{"key":"11723_CR2","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/art.1780290816","volume":"29","author":"R Altman","year":"1986","unstructured":"Altman, R. et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American rheumatism association. 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The study was registered in the German Clinical Trials Register (DRKS00029563).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Institutional review board statement"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent Statement"}}],"article-number":"25625"}}