Oral magnesium oxide for postoperative pain management in elective surgery: a systematic review of available evidence

Magnesium is an N-methyl-D-aspartate (NMDA) receptor antagonist with recognized analgesic properties. While intravenous magnesium has been extensively investigated for perioperative analgesia, evidence regarding oral magnesium, particularly magnesium oxide (MgO), remains limited in postoperative pain management. This systematic review aimed to evaluate the effectiveness of oral magnesium oxide in reducing postoperative pain and analgesic requirements in adults undergoing elective surgery. The review protocol was prospectively registered in PROSPERO (CRD42025633637) on 1.2.2025. A systematic search of four electronic databases (MEDLINE [PubMed], Scopus, EMBASE, and CENTRAL) was conducted on March 15, 2025. Randomized controlled trials involving adult patients undergoing elective surgery and receiving oral magnesium oxide compared with placebo or active comparators were included. The review followed PRISMA 2020 guidelines, and risk of bias was assessed using the Cochrane RoB 2 tool. Due to substantial clinical and methodological heterogeneity, a quantitative meta-analysis was not performed, and findings were synthesized qualitatively. Four randomized controlled trials (192 participants) met the inclusion criteria, spanning abdominal hysterectomy, tonsillectomy, third molar surgery, and colonic resection. Heterogeneity in formulation, dose, comparator, and pain assessment precluded meta-analysis, so findings were synthesised narratively. Three trials reported reduced postoperative pain: magnesium oxide versus naproxen after hysterectomy (VAS 5.47 vs. 6.62; p = 0.03), magnesium plus metamizol at days 1, 5, and 10 after tonsillectomy (p ≤ 0.015), and magnesium plus ibuprofen at rest at 24 h only after third molar surgery (mean difference − 15.08; 95% CI -29.01 to -1.14). The colonic resection trial, in which pain was a secondary outcome, found no difference. Magnesium oxide was well tolerated, with no serious adverse events. GRADE certainty was low, and no trial measured serum magnesium. Oral magnesium oxide may reduce postoperative pain in some elective surgical settings, but the evidence is limited, inconsistent, and of low certainty. Three of the four included trials reported reductions in pain intensity or analgesic consumption, though the effects were modest and, in one trial, of uncertain clinical relevance. Clinical heterogeneity, variability in magnesium formulation and dosing, and the absence of serum magnesium monitoring preclude definitive conclusions. Adequately powered trials that standardize formulation, measure serum magnesium, and evaluate dose-response are needed.