The Role of Electrolytes in Muscle Pain Syndromes: A Systematic Review and Meta-Analysis With Implications for Temporomandibular Disorder

Background: Temporomandibular disorders (TMDs) are a major cause of chronic orofacial pain, with myalgia of the masticatory muscles being central to symptom burden. Electrolyte modulation, particularly magnesium, may influence neuromuscular excitability and nociceptor sensitization, but no systematic review has synthesized the evidence for muscle pain syndromes or its relevance to TMD. Objectives: To evaluate the efficacy of electrolyte supplementation (magnesium, sodium, calcium, and potassium) in reducing muscle cramps and myalgia, and to explore the biological plausibility and potential extrapolation to TMD-related myofascial pain. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251120631). PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from January 1995 to August 2025. Randomized or quasi-randomized trials of electrolyte supplementation for cramps or myalgia were eligible. Data extraction and risk-of-bias assessment (RoB 2 tool) were performed independently by 2 reviewers. Meta-analyses used random-effects models in R (v4.4.3) and Python (v3.11). Results: Thirteen trials were included. Magnesium was most frequently studied (10 RCTs). In pregnancy-associated cramps (4 trials, N≈364), magnesium significantly reduced cramp frequency compared with placebo (pooled RR 1.35, 95% CI: 1.05-1.74, P = .02). In nocturnal or persistent leg cramps in adults (4 trials, N≈396), no significant effect was found (MD −0.42 cramps/week, 95% CI: −1.15 to 0.31, P = .26). Intravenous magnesium showed no benefit in older adults, but a perioperative trial demonstrated reduced fasciculations and postoperative myalgia. Sodium-based solutions reduced cramp susceptibility in exercise and cirrhosis, while calcium and potassium lacked supportive evidence. Risk of bias was generally low to moderate. Conclusion: Magnesium supplementation benefits pregnancy-related cramps but shows inconsistent effects in other populations. Sodium-based interventions are context-specific, and calcium and potassium remain unsupported. Magnesium is the most plausible candidate for translation to TMD myalgia, warranting targeted clinical trials.