Blunted Niacin Skin Flushing Response in Mood Disorders: A Meta-Analysis of Case-Control Studies

Mood disorders (MDs), including depressive disorder (DD) and bipolar disorder (BD), represent a major global health burden, yet the absence of objective biomarkers has persistently hindered their accurate clinical diagnosis. The niacin skin flushing response (NSFR) has shown promise as a potential biomarker; however, inconsistencies in diagnostic efficacy and response characteristics across studies have limited its utility. This meta-analysis aims to systematically evaluate the NSFR in MD patients to address these discrepancies.

A comprehensive search of PubMed, Embase, Cochrane Library, and Scopus databases was conducted for articles published through May 2025, identifying 18 eligible case-control studies involving 1848 participants (888 MD patients and 960 HC). Random-effects models were used to assess the degree, speed, and sensitivity of NSFR, while subgroup analyses and meta-regression explored potential sources of heterogeneity.

MD patients exhibited markedly blunted NSFR, characterized by reduced degree and speed of response (standardized mean difference [SMD] = -0.59, 95% confidence interval [CI]: [-1.12; -0.05] and SMD = 0.72, 95% CI: [0.35; 1.10]), while no statistically significant difference in NSFR sensitivity was observed (SMD = 0.51, 95% CI: [-0.18; 1.20]). Subgroup analyses identified substantial heterogeneity across detection methods, geographical regions, and control sources, highlighting the need for standardized protocols. Meta-regression analyses indicated that sample size, publication year, gender distribution, and age did not significantly affect outcomes, further strengthening the robustness of our findings.

This study reinforces the potential of NSFR as a biomarker for MD and highlights the critical need to address heterogeneity through standardized methodologies in future research to enhance its diagnostic reliability.