Potential role of additives in ultraprocessed foods and dietary supplements: a double-edged influence on advanced glycation end product formation and receptor for advanced glycation end product modulation in diabetic and geriatric complications—a perspective review

Abstract Background: Ultraprocessed foods (UPFs) and dietary supplements contain multiple additives that exert a dual influence on metabolic health. On the one hand, they can promote the formation of advanced glycation end products (AGEs); on the other hand, they may supply bioactive compounds capable of modulating the receptor for Advanced Glycation End Products (RAGE). Excessive AGE accumulation is associated with oxidative stress, persistent low-grade inflammation, and the progression of diabetes-related and age-associated disorders. Methods: This perspective review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines using a narrative synthesis framework. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Embase to identify studies addressing dietary AGEs (dAGEs), UPFs, food-processing methods, RAGE signaling pathways, and their implications for diabetes and aging. Owing to heterogeneity in study designs and reported outcomes, findings were synthesized qualitatively rather than through meta-analysis. Results: Available evidence consistently demonstrates that high-temperature food processing and sugar-dense UPFs enhance AGE formation and activate RAGE signaling, contributing to metabolic dysfunction and chronic inflammatory responses. In contrast, certain additives and innovative processing approaches, including antioxidant incorporation, fermentation, encapsulation technologies, and bioengineered enzymatic interventions, have the potential to limit glycation and mitigate RAGE-mediated effects. Experimental studies and limited clinical evidence indicate that strategically reformulated UPFs may help reduce dAGE exposure when guided by biochemical principles and regulatory oversight. Conclusion: UPFs and dietary supplements play dual roles, both promoting AGE formation and modulating RAGE activity. Although conventional processing practices increase glycotoxin accumulation, emerging food technologies and functional additives offer promising strategies to reduce AGE-related health risks, particularly among diabetic and older populations. Strengthening regulatory frameworks focused on AGE reduction, product reformulation, and dietary awareness may help mitigate metabolic complications.