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A rat model tested multiple HA molecular weights to identify the most effective form for alleviating OA, followed by a clinical trial to confirm its benefit. In rats, HA lowered joint swelling, increased HA levels in serum and synovial fluid, reduced pro-inflammatory cytokines, and decreased MMPs, iNOS, and COX-2, especially for high-MW HA.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/role-of-oral-hyaluronic-acid-for-joint-health-insights-from-rat-models-and-clinical-trials/408039/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/role-of-oral-hyaluronic-acid-for-joint-health-insights-from-rat-models-and-clinical-trials/408039.png","ImageObject",300,407,{"name":92,"@type":93},"Mary Man","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main research question about hyaluronic acid in this study?","Question",{"text":113,"@type":114},"The study investigates whether oral hyaluronic acid can improve joint health in osteoarthritis and how different molecular weights affect its efficacy.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was the molecular weight of HA evaluated?",{"text":118,"@type":114},"Different HA molecular weights were tested in a rat OA model to identify the form most effective at alleviating OA, which was then carried into a clinical trial.",{"name":120,"@type":111,"acceptedAnswer":121},"What did the clinical trial show about symptoms and outcomes?",{"text":122,"@type":114},"The clinical trial indicated that HA significantly decreased pain, stiffness, and physical function based on WOMAC scores, with no significant impact on blood and urine indices.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},408039,1790739923,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":41,"preview_page_count":4},7421720224475,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","OPEN ACCESS  \nEDITED BY  \nChunyou Wan,  \nTianjin University, China  \nREVIEWED BY  \nLukas Kubala,  \nInstitute of Biophysics, Academy of Sciences of the Czech Republic, Czechia Saraswathy Nagendran,  \nMithibai College of Arts, India  \n*CORRESPONDENCE  \nJunying Bai  \n [baijunying@swu.edu.cn](baijunying@swu.edu.cn)[ ](baijunying@swu.edu.cn)Shumao Cui  \n [cuishumao@jiangnan.edu.cn](cuishumao@jiangnan.edu.cn)[ ](cuishumao@jiangnan.edu.cn)Haining Shi  \n [shihn@bloomagebiotech.com](shihn@bloomagebiotech.com)[ ](shihn@bloomagebiotech.com)RECEIVED 23 August 2025 REVISED 03 November 2025 ACCEPTED 13 November 2025 PUBLISHED 17 December 2025  \nCITATION  \nWang B, Wang F, Zhang T, Bai J, Cui S and Shi H (2025) Role of oral hyaluronic acid for joint health: insights from rat models and clinical trials.  \nFront. Nutr. 12:1691328 .  \ndoi: 10.3389/fnut.2025.1691328  \nCOPYRIGHT  \n© 2025 Wang, Wang, Zhang, Bai, Cui and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nTYPE Original Research PUBLISHED 17 December 2025 DOI 10.3389/fnut.2025.1691328  \nRole of oral hyaluronic acid for joint health: insights from rat models and clinical trials  \nBotao Wang 1, Fengli Wang 1, Tianmeng Zhang 1,2, Junying Bai3*, Shumao Cui4* and Haining Shi 1*  \n1Bloomage Biotechnology Co., Ltd., Jinan, China, 2Key Laboratory of Industrial Biotechnology, Ministry of Education and School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China, 3Citrus Research Institute, Southwest University, Chongqing, China, 4State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China  \nBackground: Early studies have demonstrated the significant potential of hyaluronic acid (HA) in alleviating osteoarthritis (OA); however, the relationship between different molecular weights (MWs) and efficacy remains unclear. Methods: The rat model was used to evaluate the effects of different MWs of HA on OA and to identify the MW that was most effective in alleviating OA. Based on this, a clinical trial was conducted to verify the selected HA’s clinical efficacy. Results: The results showed that HA significantly reduced joint swelling in rats, dramatically increased HA content in the serum and joint synovial fluid, decreased serum and joint synovial fluid levels of pro-inflammatory cytokines, and reduced the expression of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) when compared with the OA group, especially high-MW HA. Importantly, these protective roles may be attributed to the immune regulation of HA. Clinical trial results indicated that HA significantly decreased pain, stiffness, and physical function of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and had no significant impact on blood and urine indices.  \nConclusion: Our findings suggest that oral supplementation with HA can reduce the progression of arthritis, pain, and cartilage damage, and can be anew strategy to relieve joint discomfort.  \nKEYWORDS  \nhyaluronic acid, osteoarthritis, different molecular weights, clinical trial, nutrition  \n1 Introduction  \nOsteoarthritis (OA) is one of the most common forms of arthritis and a leading cause of global disability ( 1–3). Current strategies focus on alleviating the symptoms of OA, including Taylor spatial frame, and non-steroidal anti-inflammatory drugs (4, 5), etc. Comprehensive application of high tibial osteotomy, chronic distraction tissue regeneration technology, and computer-assisted external fixation technology showed a pro","cbCaihpVL0qqUM0i","https://ap.wps.com/l/cbCaihpVL0qqUM0i","pdf",6909578,12,"English","# Background\n# Methods\n## Animal model assessment\n## Clinical trial verification\n# Results\n## Effects on inflammation and biomarkers\n## Effects on WOMAC pain and function\n# Conclusion\n# Keywords","[{\"question\":\"What is the main research question about hyaluronic acid in this study?\",\"answer\":\"The study investigates whether oral hyaluronic acid can improve joint health in osteoarthritis and how different molecular weights affect its efficacy.\"},{\"question\":\"How was the molecular weight of HA evaluated?\",\"answer\":\"Different HA molecular weights were tested in a rat OA model to identify the form most effective at alleviating OA, which was then carried into a clinical trial.\"},{\"question\":\"What did the clinical trial show about symptoms and outcomes?\",\"answer\":\"The clinical trial indicated that HA significantly decreased pain, stiffness, and physical function based on WOMAC scores, with no significant impact on blood and urine indices.\"}]","Role of oral hyaluronic acid for joint health: insights from rat models and clinical trials | PDF",1790577892]