Squalene supplementation to mitigate Type 2 Diabetes

Functional foods have recently gained traction as a critical component in practical chronic disease mitigation. Squalene is one such bioactive triterpene compound that has attracted research interest, specifically in relation to type 2 diabetes. Evidence from human clinical trials, animal studies, and cellular studies has produced numerous analytical studies supporting improved metabolic effects with squalene supplementation on endothelial cell function, low-density lipoprotein (LDL) cholesterol, oxidative stress, and antioxidant enzyme activity. However, despite squalene's favorable mechanistic outlooks, practical issues arise in daily implementation, as with other bioactive compounds, with natural bioavailability, absorption kinetics, and dose-dependent relationships.          Current research on squalene primarily focuses on biochemical pathways in relation to dermatological care, cardiovascular regulation, and vaccine formulation capabilities. Only recently has squalene gained prominence in its ability to mitigate chronic conditions such as type 2 diabetes. This recent evidence extends on squalene's previously documented biochemical effects, uniquely positioning it as a strong tool for daily supplementation for the regulation of type 2 diabetes through Nuclear factor kappa B (NF-κB)/ Inhibitor of Kappa B Alpha (IκB-α) inhibition, Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) activation, 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) reductase-mediated lipid regulation, and the upregulation of insulin-sensitivity markers Sirtuin 1 (SIRT1), Insulin Receptor Substrate 1 (IRS1), and Protein Kinase AMP-Activated Catalytic Subunit Alpha 2 (PRKAA2) in diabetic adipocytes.          This review is the first to examine squalene's impact across the translational research hierarchy trials in type 2 diabetes, focusing on shared pharmacological and biochemical effects. This review will also highlight areas of divergence in reported effects and note where areas of further study are necessary. These results are synthesized to evaluate the translational potential of squalene as a bioactive compound for type 2 diabetes-related metabolic dysfunction. Based on currently available human evidence, 600 mg/day appears to be the most evidence-supported dose for lipid, antioxidant, inflammatory, and cellular energy-related outcomes; however, this dose should be interpreted as a candidate dose for future validation rather than as a definitive clinical recommendation.  Novelty: This study is among the first to integrate human, animal, and cellular studies on squalene supplementation for diabetes prevention to identify discrepancies among models and to identify areas for further study. Keywords: Squalene, Dosage, Type 2 Diabetes, Biochemical Outcomes, Human Trials, Animal Studies, Cellular Studies, Bioavailability Sources.