Kynurenine metabolite changes in individuals with alcohol use disorder: A systematic review and meta-analysis

Growing evidence suggests an abnormal metabolism of kynurenine in individuals with alcohol use disorder (AUD). This systematic review and meta-analysis was aimed at assessing the possible differences in kynurenine metabolites between individuals with AUD and controls.

We searched PubMed, Embase, and Web of Science databases and included any clinical studies comparing the peripheral blood levels of at least one metabolite, between individuals with AUD and controls without AUD. Random-effects meta-analyses were conducted to generate pooled standardized mean differences (SMD). Subgroup analyses and meta-regression analyses were conducted.

A total of seven eligible studies with 572 participants were included. The peripheral blood levels of kynurenine (SMD = 0.58; p = 0.004) along with the ratio of kynurenine and tryptophan (SMD = 0.73; p = 0.002) were higher in individuals with AUD, while kynurenic acid levels (SMD = -0.81; p = 0.003) were reduced in individuals with AUD compared to controls. The peripheral blood levels of tryptophan along with the ratio of kynurenic acid and kynurenine were unaltered. Subgroup analyses confirmed these results.

Our results suggested a shift in the tryptophan metabolism to the kynurenine pathway and a down-regulation of the potentially neuroprotective kynurenic acid in individuals with AUD.