Zinc-based therapies for prevention and treatment of vulvovaginal candidiasis: a systematic review and meta-analysis

Abstract

BACKGROUND: Zinc is essential for epithelial integrity and antifungal immunity and may influence host-pathogen interactions in vulvovaginal candidiasis (VVC). However, the relationship between zinc status, zinc-based interventions, and VVC pathogenisis remains unclear. We aimed to assess the clinical efficacy of zinc-based interventions for recurrence prevention and to examine their effects on Candida virulence and inflammatory pathways. METHODS: We systematically searched the MEDLINE, Scopus, the Cochrane Central Register, and trial registries from inception to September 2025. We included observational, interventional, and experimental studies that evaluated zinc status or zinc-based therapies in VVC. Random-effects meta-analyses were used to estimate the pooled standardized mean differences (SMD) for zinc concentrations with subgroup analyses by sample type and pregnancy status. Risk ratio and risk difference for recurrence outcomes were calculated using Fisher's exact test. RESULTS: = 9.14, df = 1, p = 0.003), with a much larger effect in pregnant women (SMD - 2.19, 95% CI -3.19 to - 1.18) than in non-pregnant women (SMD - 0.55, 95% CI -0.89 to - 0.21). One RCT (n = 68) showed that zinc supplementation produced a numerically lower 90-day reinfection rate that did not reach statistical significance (28.6% vs. 48.5%, RR = 0.59, 95% CI: 0.31-1.11, p = 0.134). One RCT (n = 192) reported improved pruritus with adjunctive zinc-containing therapy (P < 0.005). Experimental studies demonstrated that zinc restriction upregulates PRA1 expression, enhancing neutrophil-mediated inflammation, while zinc supplementation or zinc oxide nanoparticles downregulate virulence factors (SAP1-3) and attenuate inflammation without reducing fungal burden. CONCLUSIONS: Zinc deficiency is associated with VVC, with a larger effect in pregnant women likely reflecting altered zinc physiology in pregnancy. Lower zinc levels in VVC may reflect a host nutritional immunity rather than a pre-existing deficiency, and causality cannot be established from the available cross-sectional evidence. Clinical trials remain insufficient to support zinc-based therapies for routine use in VVC. TRIAL REGISTRATION: Not applicable. REGISTRATION: The protocol was prospectively registered in PROSPERO (CRD420251152091).