Hidden Industrial Trans-Fatty Acids: Mechanistic Insights into Dyslipidemia, Cardiovascular Disease, and Metabolic Dysfunction-Associated Steatotic Liver Disease

Trans-fatty acids (TFAs), particularly industrially produced TFAs (iTFAs), are linked to dyslipidemia, cardiovascular disease (CVD), and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite regulatory efforts, "hidden" TFAs persist in processed foods, posing ongoing health risks. This narrative review synthesizes evidence on the biochemical and metabolic impacts of the most studied TFAs, focusing on dyslipidemia, CVD, and MASLD, and highlights gaps in research and policy. Available data suggest that iTFAs, which are dominant in modern diets, were associated with elevated low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein (a), reduced high-density lipoprotein cholesterol (HDL-C), exacerbating atherosclerosis, increasing hepatic lipogenesis, oxidative stress, and inflammation and driving MASLD progression to fibrosis, whereas ruminant TFAs (rTFAs) showed neutral or beneficial effects. Epigenetic modifications (e.g., DNA methylation, miRNA alterations) induced by TFAs may further worsen metabolic dysfunction. Analytical challenges and inconsistent food labeling make it difficult to assess TFAs intake. Global disparities in TFAs regulations persist, but some regions still exceed recommended limits. Hidden iTFAs represent a critical public health issue, necessitating stricter policies, improved labeling, and consumer education. Future research should prioritize human studies on TFA-induced epigenetic changes and develop healthier fat alternatives. Eliminating residual iTFAs from the food supply is essential to mitigate cardiometabolic risks globally.