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ORIGINAL RESEARCH article

Front. Nutr.

Sec. Clinical Nutrition

This article is part of the Research TopicPrecision Diagnostics and Prevention in Bone and Joint Diseases: From Molecular Mechanisms to Clinical TranslationView all 4 articles

Role of Oral Hyaluronic Acid for Joint Health: Insights from Rat Models and Clinical Trials

Provisionally accepted
Botao  WangBotao Wang1Fengli  WangFengli Wang1Tianmeng  ZhangTianmeng Zhang2Junying  BaiJunying Bai3*Shumao  CuiShumao Cui2Hai Ning  ShiHai Ning Shi1
  • 1Bloomage Biotechnology Co Ltd, Jinan, China
  • 2Jiangnan University, Wuxi, China
  • 3Southwest University, Chongqing, China

The final, formatted version of the article will be published soon.

Background: 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. Conclusion: Our findings suggest that oral supplementation with HA can reduce the progression of arthritis, pain, and cartilage damage, and can be a new strategy to relieve joint discomfort.

Keywords: Hyaluronic Acid, Osteoarthritis, Different molecular weights, Clinical Trial, nutrition

Received: 23 Aug 2025; Accepted: 13 Nov 2025.

Copyright: © 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) or licensor 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.

* Correspondence: Junying Bai, baijunying@swu.edu.cn

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