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 volume of research 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 subsequently, to apply such to 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, resulting in an overall categorization of the informativeness of an individual study, or study quality. In a case study application 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, due primarily to low relevance to human safety (e.g., use of an acute high dose during neonatal lifestages) and limited reliability in study conduct and reporting. 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.