Sodium benzoate 1.25g/5ml oral solution

We performed a systematic review and meta-analysis on sodium benzoate's effects on cognitive function and other psychiatric symptoms in individuals with neuropsychiatric disorders. We searched PubMed, Embase, Cochrane Library, and PsychInfo databases until September 2023. A random-effects meta-analysis was performed within a frequentist framework. To investigate the potential sources of heterogeneity, we performed subgroup analyses based on sex, dose, diagnosis, and risk of bias of the included studies. Trial sequential analyses were performed to investigate the statistical power of the synthesized studies. The certainty in evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. A total of 10 studies were included in the analysis. Sodium benzoate demonstrated a small-to-moderate positive effect on global cognitive function compared with placebo (standardized mean difference 0.40, 95% confidence interval 0.20 to 0.60, high certainty). Subgroup analyses suggested more pronounced effects in women; individuals receiving doses >500 mg/day; and individuals with early-phase Alzheimer's disease, chronic schizophrenia, or major depressive disorder. Sodium benzoate also demonstrated potential efficacy in enhancing the speed of processing, working memory, verbal learning and memory, visual learning and memory, and reasoning and problem solving. Furthermore, sodium benzoate was effective for positive psychotic symptoms but not for negative psychotic and depressive symptoms with moderate certainty. The current evidence strongly supports the positive effects of sodium benzoate on cognitive function in neuropsychiatric disorders. Further research is required to confirm its efficacy across different subtypes or stages of neurocognitive disorders and within specific cognitive domains.Systematic review registrationPROSPERO, identifier CRD42023457462.

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ImportanceFemale gender is a major risk factor for dementia; however, gender has not yet been adequately addressed by clinical trials. A recent study demonstrated that sodium benzoate, a D-amino acid oxidase inhibitor, improved cognitive function in early-phase Alzheimer disease.ObjectiveTo examine the potential gender difference in the effects of benzoate treatment on the behavioral and psychological symptoms of dementia (BPSD).Design, setting, and participantsThis post hoc secondary analysis used data from a randomized, double-masked, placebo-controlled trial conducted in 3 major medical centers in Taiwan and enrolled 97 patients with BPSD. Data were analyzed between February 2014 and November 2017.InterventionsSix weeks of treatment of 250 to 1500 mg/d of sodium benzoate or placebo.Main outcomes and measuresThe primary outcome measures were Alzheimer disease assessment scale-cognitive subscale (ADAS-cog) and Behavioral Pathology in Alzheimer Disease Rating Scale (BEHAVE-AD) scores.ResultsAmong 97 total participants (62 [64%] women; mean [SD] age, 75.4 [7.7] years), 49 patients (30 women and 19 men) were randomized to sodium benzoate, and 48 (32 women and 16 men) were randomized to placebo. Among 62 women, 6-week benzoate treatment significantly surpassed placebo in the effects on ADAS-cog performance (mean [SD] difference in score between baseline and end point, -3.1 [6.4] points vs 0 [4.5] points; Cohen d = 0.56; P = .04) but not BEHAVE-AD performance. In contrast, among 35 men, the 2 treatment groups did not differ significantly in both ADAS-cog and BEHAVE-AD scores. Compared with placebo, benzoate treatment also increased estradiol to follicle-stimulating hormone ratios among women (mean [SD] difference between baseline and end point, 0 [0.2] vs -0.1 [0.3]; P = .03).Conclusions and relevanceThese findings suggest that benzoate treatment may improve cognitive function in women with later-phase dementia. In the future, longer dose-finding trials are warranted to further clarify the efficacy of benzoate for later-phase dementia and investigate the role of sex hormones and other factors in the pathogenesis of dementia.Trial registrationClinicalTrials.gov Identifier: NCT02103673.

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With the recent approval of anti-amyloid beta (Aβ) monoclonal antibody infusion therapies for Alzheimer's disease (AD), more feasible and safter Aβ-reducing approaches are anticipated. Previous studies showed that 750-mg/day or 1000-mg/day (but not 500-mg/day) sodium benzoate treatment improved cognitive function in AD patients with excellent safety and that benzoate decreased Aβ burden in an animal AD model. The current study aimed to explore whether oral sodium benzoate was able to reduce Aβ peptides in AD patients and whether Aβ before treatment was correlated with cognitive improvement after treatment. This secondary analysis used data from a double-blind trial, in which 149 patients with mild AD were randomized to receive oral placebo or one of three benzoate doses (500, 750, or 1000 mg/day). Cognitive function and plasma Aβ 1-40 and Aβ 1-42 levels were measured before and after treatment. When compared to placebo, benzoate therapy at effective doses (750 and 1000 mg/day) reduced Aβ 1-40 and the sum of both Aβ peptides (Aβ 1-40 plus Aβ 1-42) in AD patients. Moreover, higher Aβ 1-42 levels at baseline were associated with better cognitive improvements after benzoate treatment at effective doses in the patients. The findings suggest that sodium benzoate therapy can reduce Aβ 1-40 and the total Aβ in AD patients and higher Aβ 1-42 levels before treatment predict better cognitive improvements. Due to its superior safety and convenient administration, sodium benzoate has the potential to be a novel Aβ-reducing therapy for AD treatment. TRIAL REGISTRATION: Name of trial registry: NMDA Enhancer for the Treatment of Mild Alzheimer's Disease. Identifying number: ClinicalTrials.gov Identifier: NCT03752463 ( https://clinicaltrials.gov/ct2/show/NCT03752463 ). Registration date: 2018-11-21.

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Background and hypothesisOxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia.Study designA multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed.Study resultsWe recruited our desired sample (n = 68) and retained 78% (n = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes.ConclusionsWe demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge.Trial registrationClinicalTrials.gov: NCT03510741.

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