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

Table 4 Preclinical and clinical findings on hydrogen therapy in tendinopathies and soft tissue injuries

Ref.	Year	Condition	Study type	Participants/model (number, species)	Intervention (method, dose, duration)	Key outcomes (measured)	Observed effects/significance	Main conclusions	Limitations
Meng et al[46]	2019	Tendon adhesion (post-repair)	Preclinical animal model	36 Sprague Dawley rats (tendon repair model)	Hydrogen water vs normal saline post-operative	Tendon adhesion, oxidative stress markers (MDA, 8-OHdG), antioxidant enzymes (SOD, GSH), Nrf2 pathway expression	HS group showed reduced tendon adhesion, lower MDA/8-OHdG, higher SOD/GSH. Associated with Nrf2 activation	Hydrogen water can reduce tendon adhesion and inhibit excessive inflammatory response, possibly via Nrf2 pathway	Preclinical (animal model); direct translation to humans needs validation
Sládečková et al[22]	2024	Muscle injury recovery	Review/conceptual	Athletes	Hydrogen therapy (drinking, bathing, inhaling)	Anti-oxidation, anti-inflammation, improved recovery from injury	Hydrogen therapy shows potential for muscle recovery by reducing oxidative stress and inflammation	Conceptual/review; lacks specific clinical trial data in these snippets
Ostojic[3]	2016	Soft tissue injuries (sports-related)	Small-scale pilot clinical study	36 young men with sports-related soft tissue injuries	Oral and topical H2 for 14 days, as complementary treatment	Joint flexibility, plasma viscosity, C-reactive protein, IL-6, pain scores, limb swelling	Faster return to normal joint flexibility; augmented plasma viscosity decrease. Other inflammation markers and clinical outcomes not consistently significant	Provides early support for H2 in soft tissue injuries, but limited efficacy on general inflammation markers	Small sample size; short duration; pilot nature; inconsistent reporting of all outcomes
Agyeman-Prempeh et al[47]	2025	Tendinopathy (general preclinical)	Scoping review	Various animal models (in vitro & in vivo)	Various AT treatments (general)	Tendon properties (load, stiffness, fiber structure, collagen), inflammation	Promising preclinical outcomes (improved biomechanical, histological, biochemical properties)	Poor face validity of animal models; heterogeneity in AT induction; low quality/high risk of bias in included studies; translation to clinical practice lags

AT: Achilles tendon; MDA: Malondialdehyde; 8-OHdG: 8-hydroxy-2’-deoxyguanosine; SOD: Superoxide dismutase; GSH: Glutathione; Nrf2: Nuclear factor erythroid 2-related factor 2; IL: Interleukin.