Lipid Metabolic Effects Induced by Individual and Combined Exposure to Multiple Food Additives in Human Cells

With the widespread coexistence of multiple food additives, their combined exposure has raised increasing health concerns. This study used high-content imaging to investigate the individual and combined effects of five common food additives on lipid metabolism in HepG2, Caco-2, and Jurkat T cells. In HepG2 and Caco-2 cells, all additives dose-dependently induced lipid and free cholesterol accumulation; by contrast, Jurkat T cells exhibited only sporadic statistical differences without biologically relevant dose-dependent effects. Notably, lipid droplet accumulation appeared as a relatively early and readily detectable response, though its suitability as a definitive biomarker of metabolic disturbance warrants further validation. Combined-exposure experiments, conducted in HepG2 and Caco-2 cells, revealed cell-specific interaction patterns: additive interactions dominated in HepG2 cells, while sodium benzoate and sodium cyclamate showed synergistic disruption in Caco-2 cells. These results provide in vitro evidence that multi-component combined exposure causes cell-specific lipid-related perturbations not fully captured by single-additive assessment, suggesting that mixture toxicity models should be incorporated to improve food safety evaluation.