Systematic review of metabolism and safety aspects of monosodium glutamate intake in infants and lactating mothers: a scientific and regulatory perspective

Background: Monosodium glutamate (MSG) is widely used as a flavor enhancer, and its safety has been extensively studied for decades, providing a robust evidence base. Scientific discourse has focused on its effects on neurodevelopment, metabolism, and specific populations, such as neonates, and these effects have been carefully evaluated. Regulatory agencies worldwide have periodically revisited the evidence base, emphasizing the need for updated, balanced assessments. Following PRISMA 2020 guidelines, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library up to August 2025. Eligible studies included randomized controlled trials (RCTs), observational studies, preclinical investigations, and regulatory assessments. Two independent reviewers screened 3,800 records, with moderate inter-rater agreement (Cohen's kappa = 0.40), resolving all discrepancies through consensus. Data were synthesized narratively due to heterogeneity. Risk of bias was assessed using standard tools (RoB 2, Newcastle-Ottawa, SYRCLE, and narrative appraisal). An additional 39 references provide an informed background and mechanistic context. Human studies have consistently shown efficient MSG metabolism, stable glutamate levels in breast milk, irrespective of maternal intake, and no adverse outcomes at dietary exposures. Regulatory evaluations confirmed safety, and animal studies confirmed safety at dietary levels, with effects observed only under extreme, non-physiological conditions. The risk of bias was low to moderate in human studies but higher in animal studies due to the indirectness of exposure models. Regulatory evaluations were primarily of low risk. Conclusion: Current evidence indicates that MSG is safe. Future research may further refine our understanding of developmental physiology and sensitive populations, building on the strong foundation of current evidence. A balanced interpretation of evidence is crucial for guiding public health communication and regulatory decision-making. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251239310.