Molecular hydrogen therapy in musculoskeletal conditions: An evidence-based review and critical analysis

doi:10.5312/wjo.v17.i1.111911

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World Journal of Orthopedics

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World J Orthop. Jan 18, 2026; 17(1): 111911
Published online Jan 18, 2026. doi: 10.5312/wjo.v17.i1.111911

Molecular hydrogen therapy in musculoskeletal conditions: An evidence-based review and critical analysis

Naveen Jeyaraman, Madhan Jeyaraman, Swaminathan Ramasubramanian, Shrideavi Murugan, Arulkumar Nallakumarasamy, Sathish Muthu

Naveen Jeyaraman, Madhan Jeyaraman, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nādu, India

Naveen Jeyaraman, Madhan Jeyaraman, Swaminathan Ramasubramanian, Arulkumar Nallakumarasamy, Department of Regenerative Medicine, Agathisha Institute of Stemcell and Regenerative Medicine, Chennai 600030, Tamil Nādu, India

Naveen Jeyaraman, Madhan Jeyaraman, Sathish Muthu, Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nādu, India

Shrideavi Murugan, Department of Orthopaedics, Government Tirunelveli Medical College and Hospital, Tirunelveli 627011, Tamil Nādu, India

Arulkumar Nallakumarasamy, Department of Orthopaedics, Jawaharlal Institute of Postgraduate Medical Education and Research, Karaikal 609602, Puducherry, India

Sathish Muthu, Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram 631552, Tamil Nādu, India

Author contributions: Jeyaraman M contributed to conceptualization; Jeyaraman N, Ramasubramanian S, and Murugan S contributed to manuscript writing; Jeyaraman N, Nallakumarasamy A, and Muthu S helped in manuscript revision; Jeyaraman M contributed to proofreading; Jeyaraman M contributed to administration; Ramasubramanian S and Murugan S contributed to acquiring clinical data and performing the data analysis; Muthu S contributed for image acquisition. All authors have agreed to the final version to be published and agree to be accountable for all aspects of the work.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Madhan Jeyaraman, MD, PhD, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Poonamalle High Road, Velappanchavadi, Chennai 600077, Tamil Nādu, India. madhanjeyaraman@gmail.com

Received: July 14, 2025
Revised: September 15, 2025
Accepted: November 13, 2025
Published online: January 18, 2026
Processing time: 180 Days and 22.5 Hours

Abstract

Molecular hydrogen (H₂) demonstrates selective antioxidant and anti-inflammatory properties with therapeutic potential across musculoskeletal conditions including osteoarthritis, rheumatoid arthritis, exercise-induced muscle damage, chronic pain syndromes, tendinopathies, and muscle atrophy. This review critically evaluates preclinical and clinical evidence for H₂ therapy and identifies research gaps. A comprehensive search of PubMed, EMBASE, and Cochrane Library (up to April 2025) yielded 45 eligible studies: 25 preclinical and 20 clinical trials. Preclinical models consistently showed reductions in reactive oxygen species, inflammatory cytokines, and improved cell viability. Clinical trials reported symptomatic relief in osteoarthritis, decreased Disease Activity Score 28 in rheumatoid arthritis, and accelerated clearance of muscle damage markers. Delivery methods varied - hydrogen-rich water, gas inhalation, and saline infusion - hindering direct comparison. Mechanistic biomarkers were inconsistently reported, limiting understanding of target engagement. Common limitations included small sample sizes, short durations, and protocol heterogeneity. Despite these constraints, findings suggest H₂ may serve as a promising adjunctive therapy via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Future research should prioritize standardized delivery protocols, robust mechanistic endpoints, and longer-term randomized trials to validate clinical efficacy and optimize therapeutic strategies.

Keywords: Molecular hydrogen; Musculoskeletal disorders; Oxidative stress; Anti-inflammation; Clinical evidence

Core Tip: Molecular hydrogen therapy exhibits potent antioxidant, anti-inflammatory, and cytoprotective effects across diverse musculoskeletal conditions. This review synthesizes evidence from 45 studies - spanning osteoarthritis, rheumatoid arthritis, muscle damage, chronic pain, and atrophy - highlighting promising symptomatic relief and mechanistic plausibility. However, variability in delivery methods, sample sizes, and endpoints demands standardized trials with biomarker-driven designs to validate molecular hydrogen’s efficacy and guide clinical integration.