Sodium benzoate is an aromatic carboxylate salt with broad-spectrum preservative capacity and nitrogen-scavenging ability. Sodium benzoate induces apoptosis. Sodium benzoate inhibits microbial respiratory enzyme systems in undissociated form under acidic conditions and reduces growth of bacteria, molds, and yeasts. Sodium benzoate conjugates with Gly via CoA to generate hippurate for renal excretion to divert ammonia nitrogen and reduce blood ammonia. Sodium benzoate is used for preservation of acidic foods and beverages, liquid formulation storage, and research on urea cycle disorders hyperammonemia and hepatic encephalopathy-related hyperammonia[1-4].
In vitro, co-treatment with 0.125-1mg/mL Sodium benzoate and 500μM aluminum maltolate for 48 hours increased PC12 cell viability, increased catalase activity, and decreased reactive oxygen species levels[5]. Treatment with 5-20mM Sodium benzoate for 24 hours decreased AC16 cell viability and proliferation, caused mitochondrial membrane potential depolarization, increased BAX/BCL2 ratio, and up-regulated Cleaved-Caspase3[6]. Treatment with 1.0-2.0mg/mL Sodium benzoate for 24-48 hours increased micronucleus formation and caused chromosome breakage, sister chromatid separation, and gaps in lymphocytes[7].
In vivo, administration of 1g/kg Sodium benzoate to C57BL/6J mice for 20 weeks increased fasting blood glucose, decreased fasting insulin secretion, impaired glucose tolerance. Sodium benzoate up-regulated pancreatic IL-18, TNF-α, Bax, and Caspase-9, down-regulated Bcl-2, and caused acinar atrophy around islets, vacuolar degeneration, and slight lymphocyte infiltration[8]. Intraperitoneal injection of 2.5-10mmol/kg Sodium benzoate to spf/Y and CD-1/Y mice for 1 hour decreased brain ammonia and glutamine and increased brain glutamate in spf/Y mice. Injection of 5-10mmol/kg Sodium benzoate increased brain and liver ammonia and serum ammonia and decreased brain and liver ATP, free CoA, and acetyl-CoA[9]. Administration of 125-500mg/kg Sodium benzoate to Swiss mice for 8 weeks. Sodium benzoate decreased blood RCC, WCC, and lymphocyte counts, increased MDA and ALT, and decreased TAC, TNF-α, and IL-10[10].
References:[1] Asejeje FO, Akinola KD, Abiola MA. Sodium benzoate exacerbates hepatic oxidative stress and inflammation in lipopolysaccharide-induced liver injury in rats. Immunopharmacol Immunotoxicol. 2023 Oct;45(5):558-564.
[2] Lin CH, Lane HY. Sodium benzoate treatment decreased amyloid beta peptides and improved cognitive function among patients with Alzheimer's disease: secondary analysis of a randomized clinical trial. Transl Psychiatry. 2025 Aug 5;15(1):264.
[3] Asero R. Sodium benzoate-induced pruritus. Allergy. 2006 Oct;61(10):1240-1.
[4] Walczak-Nowicka ŁJ, Herbet M. Sodium Benzoate-Harmfulness and Potential Use in Therapies for Disorders Related to the Nervous System: A Review. Nutrients. 2022 Apr 2;14(7):1497.
[5] Arabsolghar R, Saberzadeh J, Khodaei F, et al. The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line. Res Pharm Sci. 2017 Oct;12(5):391-400.
[6] Tang N, Wu Z, Zhou Y, et al. Sodium benzoate induces cardiotoxicity by suppressing the PI3K/AKT/GSK3β signaling axis: An integrated network toxicology and experimental study. Ecotoxicol Environ Saf. 2026;323:120618.
[7] Pongsavee M. Effect of Sodium Benzoate Preservative on Micronucleus Induction, Chromosome Break, and Ala40Thr Superoxide Dismutase Gene Mutation in Lymphocytes. BioMed Res Int. 2015;2015:103512.
[8] Li D, Zhang L, Yang P, et al. Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation. Ecotoxicol Environ Saf. 2024;270:115877.
[9] Ratnakumari L, Qureshi IA, Butterworth RF. Effect of sodium benzoate on cerebral and hepatic energy metabolites in spf mice with congenital hyperammonemia. Biochem Pharmacol. 1993 Jan 12;45(1):137-146.
[10] Olofinnade A, Onaolapo A, Onaolapo O, et al. The potential toxicity of food-added sodium benzoate in mice is concentration-dependent. Toxicol Res. 2021;10(3):561-569.