Monosodium glutamate (MSG) is a well-studied food additive. In addition to numerous authoritative assessments of safety, a substantial volume of research is ongoing with MSG; this includes a growing number of studies assessing the ameliorating potential of various substances against purported MSG-induced toxicity. This work set out to develop an approach for evaluating the combined reliability and relevance of these types of investigations as part of ingredient safety assessments, and to apply this approach in a case study of MSG publications involving co-exposures with other substances. The approach assesses the reliability of the studies utilizing SciRAP, and the relevance in context of study design, dose relevance, and biological validity. Considered together, these assessments result in an overall categorization of the informativeness of an individual study, or study quality. In a case study application of the approach to 39 studies assessing MSG toxicity and ameliorative properties of a variety of substances, no publications were deemed of ‘high’ study quality for the purpose of assessing safety, primarily due to limited reliability in study conduct and reporting and/or low relevance to human safety (e.g., use of an acute high dose during neonatal lifestages). The approach herein can facilitate objective assessments of the quality of MSG safety or toxicity studies and could also be tailored to other food additives or ingredients.