Hypoglycemic Effect of Astaxanthin Oil–Fish Oil Complex in Mice With Type 2 Diabetes

ABSTRACT Diabetes mellitus (DM), a chronic metabolic disorder, is characterized by disrupted glucose homeostasis, and its escalating global prevalence underscores the critical need for safe dietary interventions. This study investigated the hypoglycemic and hepatoprotective potential of a novel formulation combining astaxanthin oil (AO) and fish oil (FO) as an adjuvant nutritional strategy. The efficacy of the AO–FO complex was evaluated using the insulin‐resistant HepG2 cell model in vitro and high‐fat diet (HFD)‐fed insulin‐resistant mice in vivo. While individual treatments with AO and FO improved basic insulin sensitivity, their co‐administration exhibited enhanced efficacy in promoting cellular glucose consumption. Notably, the combined formulation was associated with changes in key glucose metabolism‐related indices, including glucose‐6‐phosphate, pyruvate kinase, hexokinase, and significantly mitigated oxidative stress markers. In vivo, the AO‐FO complex showed greater effects on decreasing fasting blood glucose, improving oral glucose tolerance, and ameliorating systemic dyslipidemia compared to singular oil treatments. Furthermore, histopathological evaluations revealed a marked attenuation of hepatic steatosis and pancreatic islet damage following the combined treatment. Collectively, these findings support the potential combined benefits of astaxanthin and omega‐3 polyunsaturated fatty acids for improving glucose homeostasis, suggesting that the AO–FO complex may be a candidate functional food for DM management.