The Effects of Carnosine on Cognitive Function and Mental Health-A Systematic Review and Meta-Analysis

Introduction: Previous research has shown that L-carnosine (β-alanyl-L-histidine) can reduce cognitive decline and improve mental health outcomes, but an updated systematic review of the effects of carnosine alone or in combination with other supplemental nutrients or bioactive compounds on these interconnected outcomes is lacking. Methods: We searched multiple databases from 1 January 2006 to 30 June 2025 for clinical trials evaluating the effects of all forms of carnosine (e.g., L-carnosine, zinc-L-carnosine) alone or in combination with other supplements on cognition, brain structure and function, mood, depression, or quality of life (QOL) outcomes. The Cochrane Risk of Bias (ROB) 2.0 tool was used to assess the ROB in randomized controlled trials (RCTs). When data were sufficient, random-effects meta-analyses were conducted. Strength of evidence (SoE) across studies was rated using the GRADE approach. Results: A total of 13 distinct studies (12 RCTs; 1 single-arm trial) involving healthy adults and patients with psychiatric or neurocognitive disorders were included. Studies were also heterogeneous in carnosine supplement dosage and duration. Overall 58% of included RCTs were rated 'some concerns' for ROB. Ten RCTs evaluated cognitive function, seven RCTs and one single-arm trial assessed mood and depression, four RCTs measured QOL, and three RCTs examined brain structure and function. Results from five RCTs found no significant differences in the majority of the cognitive function measures between L-carnosine supplement and placebo, but random-effects meta-analysis of three RCTs from a single research team found that anserine/L-carnosine supplementation significantly improved WMS-LM2 scores (pooled net change = 1.70; 95% CI 0.19, 3.2; I² = 58.3%) but not WMS-Local Memory Immediate Recall (LM1) scores (pooled net change = 0.76; 95% CI -0.18, 1.71; I² = 8.5%). Additionally, meta-analysis results showed that L-carnosine combined with anserine or antioxidant supplementation significantly improved the MMSE score compared to placebo (pooled net change = 0.62; 95% CI 0.23, 1.01), with small statistical heterogeneity (I² = 21.3%). Most of the studies did not show significant effects in a wide range of mood and depression outcome measures or health-related QOL (data cannot be meta-analyzed). Conclusions: A low strength of evidence suggests that L-carnosine supplement combined with anserine or antioxidants can slow cognitive function decline among healthy elderly or patients with probable Alzheimer's Disease or mild neurocognitive disorder. More high-quality RCTs are needed to verify these findings and to improve the certainty level of this body of evidence.