Trans Fatty Acids

Human studies have established a positive association between the intake of industrial trans fatty acids and the development of cardiovascular diseases, leading several countries to enact laws that restrict the presence of industrial trans fatty acids in food products. However, trans fatty acids cannot be completely eliminated from the human diet since they are also naturally present in meat and dairy products of ruminant animals. Moreover, bans on industrial trans fatty acids have not yet been instituted in all countries. The epidemiological evidence against trans fatty acids by far overshadows mechanistic insights that may explain how trans fatty acids achieve their damaging effects. This review focuses on the mechanisms that underlie the deleterious effects of trans fatty acids by juxtaposing effects of trans fatty acids against those of cis-unsaturated fatty acids and saturated fatty acids (SFAs). This review also carefully explores the argument that ruminant trans fatty acids have differential effects from industrial trans fatty acids. Overall, in vivo and in vitro studies demonstrate that industrial trans fatty acids promote inflammation and endoplasmic reticulum (ER) stress, although to a lesser degree than SFAs, whereas cis-unsaturated fatty acids are protective against ER stress and inflammation. Additionally, industrial trans fatty acids promote fat storage in the liver at the expense of adipose tissue compared with cis-unsaturated fatty acids and SFAs. In cultured hepatocytes and adipocytes, industrial trans fatty acids, but not cis-unsaturated fatty acids or SFAs, stimulate the cholesterol synthesis pathway by activating sterol regulatory element binding protein (SREBP) 2-mediated gene regulation. Interestingly, although industrial and ruminant trans fatty acids show similar effects on human plasma lipoproteins, in preclinical models, only industrial trans fatty acids promote inflammation, ER stress, and cholesterol synthesis. Overall, clearer insight into the molecular mechanisms of action of trans fatty acids may create new therapeutic windows for the treatment of diseases characterized by disrupted lipid metabolism.

After the discovery that trans fat increases the risk of coronary heart disease, trans fat content of foods have considerably changed. The aim of this study was to systematically review available data on intakes of trans fat and its dietary sources in general populations worldwide. Data from national dietary surveys and population studies published from 1995 onward were searched via Scopus and websites of national public health institutes. Relevant data from 29 countries were identified. The most up to date estimates of total trans fat intake ranged from 0.3 to 4.2 percent of total energy intake (En%) across countries. Seven countries had trans fat intakes higher than the World Health Organization recommendation of 1 En%. In 16 out of 21 countries with data on dietary sources, intakes of trans fat from animal sources were higher than that from industrial sources. Time trend data from 20 countries showed substantial declines in industrial trans fat intake since 1995. In conclusion, nowadays, in the majority of countries for which data are available, average trans fat intake is lower than the recommended maximum intake of 1 En%, with intakes from animal sources being higher than from industrial sources. In the past 20 years, substantial reductions in industrial trans fat have been achieved in many countries.

Intake of trans fatty acids (TFA), which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO) bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived-dairy products and meat) on endothelial NF-κB activation and nitric oxide (NO) production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans)), Linoelaidic (trans-C18:2 (9 trans, 12 trans)), and Transvaccenic (trans-C18:1 (11 trans)) for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses) did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation.

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.