Safety and efficacy of sodium benzoate for patients with mild Alzheimer’s disease: a systematic review and meta-analysis

Abstract

ABSTRACT Objective Alzheimer’s disease (AD) is the most common neurodegenerative disorder. A key factor in its pathogenesis is the dysfunction of the N-methyl-D-aspartate (NMDA) receptor due to D-serine degradation by D-amino acid oxidase. Benzoate has been suggested to enhance NMDA receptor function, potentially benefiting early-phase AD. This study aimed to synthesize evidence from randomized clinical trials (RCTs) on the safety and efficacy of sodium benzoate in AD patients. Methods We followed PRISMA statement guidelines during the accommodation of this systematic review and meta-analysis. A computer literature search (PubMed, Scopus, Web of Science, and Cochrane Central) was conducted. We included RCTs that compared sodium benzoate with placebo regarding cognitive functions. The primary outcome measure was the Alzheimer’s disease assessment scale-cognitive subscale, pooled as the mean difference between the two groups from baseline to the endpoint. The secondary outcomes measures are the clinician's interview-based impression of change plus caregiver input, catalase, and superoxide dismutase antioxidants. Results Three RCTs (described in four articles) with 306 patients were included in this study. Sodium benzoate significantly improved the ADAS-cog score compared with placebo (MD -2.13 points, 95% CI [-3.35 to -0.90]; P= 0.0007). Conclusion Sodium benzoate is a safe drug that may improve cognitive function in patients with early-stage Alzheimer’s disease. However, the significant effect arises primarily from one small study, highlighting the need for caution in interpretation. Further research with larger sample sizes and longer durations is necessary to validate these findings and assess safety and efficacy.