Evaluating Salivary Cortisol and Alpha-Amylase as Candidate Biomarkers in Anorexia Nervosa: A Systematic Review and Meta-Analysis

<b>Objectives</b>: This systematic review and meta-analysis investigated whether salivary cortisol and alpha-amylase levels differ between patients with anorexia nervosa (AN) and healthy controls. <b>Methods</b>: A systematic literature search was conducted in PubMed, ScienceDirect, SpringerLink, and Scopus for relevant studies published up to December 2024. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical heterogeneity was assessed using Cochran's <i>Q</i> and the <i>I</i>² statistic. <b>Results</b>: Data on salivary alpha-amylase were extracted from six studies including 218 patients with AN and 220 healthy controls. No significant group difference was observed (SMD = -0.48; 95% CI, -1.05 to 0.10; <i>I</i>² = 86%), though sensitivity analysis indicated significantly lower levels in AN (SMD = -1.12; 95% CI, -2.16 to -0.09; <i>I</i>² = 82%). Salivary cortisol was assessed in 24 reports from 17 studies (517 patients with AN, 672 controls), revealing significantly higher levels in AN (SMD = 0.69; 95% CI, 0.54-0.85; <i>I</i>² = 30%). Sensitivity analyses showed stable effect sizes. Meta-regression indicated that neither age nor body mass index significantly moderated the results. <b>Conclusions</b>: Salivary cortisol may serve as a reliable, noninvasive biomarker for AN, with potential utility in early identification and prevention of disease progression.