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

Table 6 Safety profile and reported adverse events of hydrogen therapy

Safety status	Observed adverse events (type, frequency, severity)	Associated delivery method	Context/condition of study	Important safety considerations
GRAS by FDA	No toxic side effects reported in many clinical trials	All methods (HRW, inhalation, injection, topical)	General clinical use, ischemic stroke, various conditions	Ensure adequate oxygen during inhalation; avoid contaminated H2; consult healthcare provider for high/extended doses
No contraindications shown when taken as directed	Headaches (2/121, 1.7%); nasal cavity dryness (1/121, 0.8%); no significant difference vs control	H2-O2 inhalation	Knee osteoarthritis	Proper device use; avoid excessive water intake
No adverse effects/toxicity observed	None reported (qualitative improvements in energy, sleep, defecation noted)	Oral hydrogen-rich coral calcium	Autoimmune diseases (RA, SLE)	Monitor for potential effects of other components (e.g., calcium) in combined supplements
No adverse effects reported	None reported	H2-saline infusion	RA, ischemic stroke	Ensure sterile preparation and professional administration for injections
No substantially negative effect	None reported (as defined by MCID)	Hydrogen-rich water	exercise-induced muscle damage in athletes	Adherence to recommended dosages

GRAS: Generally recognized as safe; FDA: Food and Drug Administration; MCID: Minimum clinically important difference; RA: Rheumatoid arthritis; SLE: Systemic lupus erythematosus.