Serum and Plasma Zinc and Copper Levels in Oral Leukoplakia: A Systematic Review and Meta-Analysis

Background: Oral leukoplakia (OL) is a common oral potentially malignant disorder in which oxidative imbalance and altered trace-element homeostasis may contribute to pathogenesis. This systematic review and meta-analysis evaluated serum/plasma zinc and copper concentrations in patients with OL versus healthy controls. Materials and Methods: Following PRISMA and Cochrane recommendations (PROSPERO: CDR420261427977), PubMed, Scopus, Web of Science, and Cochrane were searched for observational studies comparing circulating zinc and/or copper levels in OL and controls. Study quality was assessed using the Newcastle–Ottawa Scale and certainty of evidence using GRADE. Hedges’ g with 95% confidence intervals (CIs) was pooled. Results: Ten studies including 495 participants were analyzed. Zinc concentrations were significantly lower in OL (8 studies; 431 participants; g = −1.84, 95% CI: −3.25 to −0.43; p = 0.01; I2 = 96.85%), whereas copper concentrations were significantly higher (9 studies; 449 participants; g = 1.20, 95% CI: 0.70–1.70; p < 0.001; I2 = 81.90%). Sensitivity analyses confirmed the direction of both associations. Certainty of evidence was very low. Conclusions: Patients with OL showed lower circulating zinc and higher copper concentrations than healthy controls. Given the substantial heterogeneity and very low certainty of evidence, these findings should be interpreted as group-level differences only and do not establish a specific metabolic, pathogenic, causal, or diagnostic role of Zn or Cu in OL.