Next Article in Journal
Diagnostic and Prognostic Potential of CXCL9 and CXCL10 Chemokines in Alcohol-Associated Liver Disease
Previous Article in Journal
5-Substituted 4-Thiouridines, 4-Thio-2′-deoxyuridines and Their Oligoglycol Carbonate Prodrugs as Promising Antimicrobial Agents
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 26
Issue 23
10.3390/ijms262311715
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

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

by
Mona A Hegazy
1,
Bojana Vidovic
2,
Shimaa Abobakr
3,
Aleksandra Zeljkovic
4,
Aleksandra Stefanovic
4 and
Jelena Vekic
4,*
1
Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 12556, Egypt
2
Department of Bromatology, University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia
3
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 12556, Egypt
4
Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(23), 11715; https://doi.org/10.3390/ijms262311715
Submission received: 5 October 2025 / Revised: 27 November 2025 / Accepted: 1 December 2025 / Published: 3 December 2025
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Browse Figures
Versions Notes

Abstract

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.

1. Introduction

Trans-fatty acids (TFAs) are a form of unsaturated fat where the hydrogen atoms around a carbon–carbon double bond are on opposite sides, known as a ‘trans’ configuration. This can occur in both monounsaturated (MUFA) and polyunsaturated (PUFA) fats. The TFAs can be either of industrial hydrogenation origin, i.e., industrial trans-fatty acids (iTFAs), or naturally from biohydrogenation in ruminant animals known as ruminant TFAs (rTFAs) [1].
The pervasive presence of TFAs in modern diets poses a significant public health concern, despite growing awareness of their detrimental effects. Observational and experimental epidemiological studies have provided robust evidence on the effect of TFAs on human health, in general, and the cardiovascular system. Consumption of iTFAs raises the total high-density lipoprotein cholesterol (HDL-C) ratio in the blood and the risk of coronary heart disease [2,3,4,5].
The effects of rTFAs on lipoproteins and heart diseases are unclear and data on their impact on plasma lipoproteins in humans are limited. Some epidemiological studies have shown no association between rTFAs intake and heart disease risk [2,6]. In contrast, others have shown a non-significant inverse association [7], or a non-significant positive association [3].
While overt sources of TFAs have been increasingly regulated, “hidden” trans-fats, often stemming from partially hydrogenated oils, continue to infiltrate processed foods, creating a subtle yet substantial dietary burden. This insidious intake carries profound implications for metabolic health, particularly concerning serum lipid profiles and the development of cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD), previously called non-alcoholic fatty liver disease (NAFLD).
Understanding the subtle yet significant role of hidden trans-fats is crucial for developing effective dietary interventions and public health strategies. By shedding light on the implications of these often-overlooked dietary components, this study seeks to empower individuals and healthcare professionals to make informed choices that promote metabolic well-being and mitigate the risks associated with chronic disease.
This narrative review discusses the link between hidden trans-fat consumption, dyslipidemia and its associated CVD risk, and MASLD by examining the impact of these concealed TFAs on serum lipid parameters, including low-density lipoprotein cholesterol (LDL-C), HDL-C, triglycerides (TG), and beyond. We aim to elucidate the mechanisms by which TFAs contribute to changes in the serum lipid profile and cardiometabolic risk. Furthermore, we highlight the association between hidden trans-fat intake and the pathogenesis of MASLD, a growing epidemic linked to dietary factors and metabolic dysfunction. Given the limited explicit mention of “hidden” trans-fats in the literature, this review interprets findings on industrially produced TFAs (often found in processed foods) as representative of hidden trans-fats. This approach allows for a discussion of the potential impact of TFAs that are not explicitly labeled or recognized in the diet.

2. Summary of the Most Widely Studied Trans-Fatty Acids

The presence of one or more unconjugated trans-double bonds significantly affects the physical, chemical, and biological properties of TFAs compared to the most common cis-unsaturated fatty acids. A more rigid structure and higher melting points make TFAs similar to saturated fatty acids (SFAs) [8]. In vitro and animal studies indicate that TFAs, although less potent than SFAs, promote CVD and other adverse health outcomes [9].
The major iTFAs are elaidic acid, which is a geometrical isomer of oleic acid (C18:1n-9), and linoelaidic acid, as the geometrical isomer of the essential n-6 linoleic acid (C18:2n-6) (Table 1) [10]. Most iTFAs are formed through the partial hydrogenation of vegetable oils, which may contain up to 60% TFAs [11]. Due to their solid consistency and enhanced oxidative stability, hardened vegetable oils, such as margarine and vegetable shortenings, are widely added to improve the texture and shelf life of various food products. Additionally, TFAs can be formed during the refining process of crude oils. It was estimated that processed food and oils contribute about 80% of TFAs in the modern diet [12]. Among these products, commercially baked foods (cakes, cookies, and pies), snacks, and fast foods are commonly considered the primary sources of iTFAs [13]. In addition to industrial processing, thermal food processing at home, such as baking and deep-frying, also contributes to the formation of TFAs. Not only temperature, but other factors such as food constituents (proteins, carbohydrates, and antioxidants), and the material of the frying vessel, affect the formation of TFAs [14,15]. Furthermore, research indicates that cooking with ingredients rich in isothiocyanates and polysulfides, such as garlic, onion, and broccoli sprouts, can increase the formation of the TFAs in edible oils [16].
Certain foods, such as meat, milk, and dairy products, contain natural TFAs produced through the biohydrogenation of PUFAs from feeds in the rumen of animals. However, since ruminant lipids only reach up to 4–6% TFAs, the contribution of ruminant-derived foods to overall TFA intake is minimal compared to highly processed foods [17]. Among natural TFAs, vaccenic acid is the most predominant geometrical isomer, constituting 50–80% of the total rTFAs. It is a precursor of rumenic acid, as the main isomer of conjugated linoleic acid (CLA). This conjugated TFA can also be endogenously formed after ingestion of vaccenic acid from ruminant-derived food by the activity of Δ9-desaturase [18]. Among rTFAs, palmitelaidic acid, also known as trans-palmitoleic acid, is proposed as a biomarker of high-fat dairy fat intake. It has also been suggested that it may be endogenously produced from vaccenic acid [19].
At this point, it is important to note that the two main types of fatty acids isomers are geometrical isomers, which differ in their cis or trans configurations, and positional isomers, which differ in the location of the double bond along the fatty acid chain. The formation of iTFAs through industrial partial hydrogenation, deodorization processes, and even certain home-cooking practices can promote the generation of both geometrical and positional trans isomers [14,20]. On the other hand, this specific mixture of positional and geometrical isomers does not occur in some rTFAs. This distinction in isomeric compositions is essential to the divergent biological effects attributed to iTFA and rTFA.
In the human body, TFAs can be formed by geometrical isomerisation due to free radical attack [21,22]. Additionally, there is evidence that certain gut microbes can hydrogenate dietary PUFAs like linoleic acid into various TFAs isomers, including trans-10, cis-12 CLA, which has distinct metabolic effects [23,24]. Therefore, the total “TFA burden” reflects the sum of dietary iTFAs and rTFAs intake together with endogenous TFAs formation, after accounting for TFAs catabolism.

3. Impact of Trans-Fatty Acids on Dyslipidemia and Cardiovascular Risk

Dyslipidemia, comprising elevated serum concentrations of total cholesterol (TC), TG, and LDL-C, with decreased levels of HDL-C, is among the major cardiovascular risk factors [25,26,27], and epidemiologic studies have provided convincing evidence of the adverse effects of TFAs on the serum lipid profile. It has been shown that consumption of TFA-rich food is associated with an increase in serum LDL-C, TG, and lipoprotein (a), while also leading to a decrease in HDL-C levels in adults [28,29,30,31]. Similarly, lower total cholesterol (TC) and LDL-C concentrations were observed in parallel with lower consumption of TFAs in children [32]. However, epidemiologic data are not fully complemented by mechanistic explanations of how TFAs modulate lipoprotein metabolism.

3.1. Modulation of Lipoprotein Structure and Lipid Metabolism Pathways by Trans-Fatty Acids

Recent data provide novel insights into the mechanisms by which TFAs influence body lipids (Figure 1). It has been reported that cholesterol synthesis increases when Hepa1-6 cells are treated with elaidic acid. Such an effect is presumably achieved through the overexpression of genes involved in cholesterogenesis [33]. Moreover, iTFAs may contribute to changes in the expression of other genes affecting lipid metabolism. Recent findings demonstrated higher serum elaidic acid levels, in parallel with decreased gene expressions of peroxisome proliferator-activated receptors alpha and gamma and the expression of the LDL receptor, in laying hens fed with different palm oils, compared to hens fed with soybean oil [34].
Yet, it should be emphasized that rTFAs might have divergent effects. It has been reported that vaccenic acid, the most prominent rTFA, does not induce cholesterol synthesis in hepatocytes [35]. A more recent study [36] has shown decreased expressions of genes involved in cholesterol synthesis in the liver of Golden Syrian hamsters fed with milk rich in vaccenic acid. Similarly, a diet rich in vaccenic acid reportedly exhibits favorable effects on the serum lipid profile, insulin sensitivity, and gut microbiome in pigs [37].
In addition to the effects on cholesterol synthesis, TFAs influence other aspects of lipid metabolism. Data obtained from studies, interpreted in accordance with the evolved Bradford Hill considerations, suggest that iTFAs may contribute to a reduction in the expression and activity of LDL receptors [38]. Also, it has been demonstrated that substituting PUFA with iTFAs in olive and rapeseed oils leads to an increase in the liver TG content in mice that are fed these oils. The mentioned effects presumably arise due to the overexpression of lipogenic enzymes and lower expression of mediators of beta-oxidation [39].
Novel evidence suggests that TFAs can alter the metabolic fate of phospholipids and sphingolipids. Recent research shows that iTFAs preferentially incorporate in sphingolipids, promoting their secretion and accelerating very low-density lipoprotein (VLDL) release in mice [40]. Importantly, experiments on cell lines indicated enhanced incorporation of both iTFAs (elaidate) and rTFAs (vaccinate) in ceramides and diacylglycerols, and thereby a formation of harmful lipid moieties with possible deleterious effects [41,42]. It has been suggested that TFAs may act through interactions with lipid rafts [43,44], but further research is required to fully clarify their effects.

3.2. Overview of the Impact of Trans-Fatty Acids on Vascular Oxidative Stress and Inflammation

Even though dyslipidemia-related chronic diseases are based on various pathophysiological mechanisms, multifactorial risk assessment pointed out a synergistic interplay of inflammation and oxidative stress as crucial components [45]. Current evidence indicates that excessive diet 5% elaidic acids intake accelerates atherosclerosis by promoting inflammation and oxidative stress in a mouse model of hyperlipidemia [46]. Comprehensive research of the mechanism of the inflammatory effect of TFAs has been performed, in vitro, in different cell models. It has been shown that TFAs integrate into the membranes of adipocyte, monocyte, and macrophage cells, amplifying inflammatory signaling pathways [47]. Evidenced by previous research, elaidic and linoelaidic acids activate endothelial NF-κB signaling and reduce NO in human microvesicular endothelial cells [48]. Furthermore, iTFAs promoted DNA damage-induced apoptosis by inducing mitochondrial oxidative stress [49] and inhibited cell growth by activating oxidative stress in the endoplasmic reticulum and unfolded protein response signaling pathways in SH-SY5Y cells [50]. Importantly, available data indicate that the inflammatory effects are related to iTFAs, while rTFAs have no impact or may even exhibit anti-inflammatory properties [9]. In line with this, research by Lee et al. [51] showed on isolated mice splenocytes that dietary trans-11 18:1 vaccenic acid at physiological concentrations of 50–200 μM enhanced the IL-10 and suppressed TNF-alpha production.

3.3. Human Studies Assessing the Link Between TFAs, Dyslipidemia, Oxidative Stress, Inflammation, and Cardiovascular Risk

Ongoing research continues to assess the broader health implications of TFAs consumption (Table 2), as regulatory compliance remains incomplete [52], particularly in Southeast European countries [53] and in the Eastern Mediterranean Region [54]. There is an ongoing debate about whether rTFAs and iTFAs have similar cardiometabolic effects.
Although a body of evidence confirms the contribution of TFAs to the altered serum lipid profile, oxidative stress, and inflammation, it should be noted that much of the available data comes from in vitro and animal studies exploring the effects of single, purified TFAs on specific bioactive lipid compounds. However, considering the complexity of the human diet and the diversity of both ingested [14,20] and endogenously formed TFAs [18,24], these findings can only serve as indicators of the potential effects. A complete understanding of putative effects of TFAs in humans requires further studies designed to fully appreciate the multi-faceted nature of human exposure to these compounds.
In line with the findings of cell culture and animal studies, a recent cohort study conducted in the elderly Norwegian population recorded inverse associations between rTFAs serum levels and LDL-C and TG concentrations, while direct associations were found with HDL-C [55]. Yet, it should be noted that findings from human studies are not fully consistent. For instance, significantly higher plasma TC and LDL-C levels were recorded in healthy volunteers who adhered to a 4-week diet with alpine butter as a source of rTFA [56]. Noteworthy, such an elevation of serum cholesterol concentrations might arise due to the joint influence of other lipid components of butter, instead of the effect of rTFA solely. Similarly, a systematic review by Verneque et al. [57] indicated that both rTFA and iTFA intakes are associated with worsened TC and LDL-C levels, but have inverse effects on HDL-C levels. Yet, the authors emphasized that the total effect of TFA intake depends on the dose, but also on the composition of ingested food.
Iino et al. [58] have reported that the increased proportion of elaidic acid in the phospholipids of HDL negatively affects the cholesterol uptake capacity in human sera by decreasing the fluidity of the HDL surface and the activity of lecithin-cholesterol acyltransferase (LCAT). Interestingly, it was recently shown that whole TFA intake can have variable effects on insulin sensitivity in adult carriers of distinct phenotypes of the cholesteryl ester transfer protein gene (CETP), suggesting a possible influence of TFAs on CETP activity [59]. In line with this, it was reported that overall levels of mono TFAs (trans-palmitoleic, elaidic, and vaccenic) positively correlate with TG levels in human serum [60]. Epidemiological studies reported that the distinct TFA content of plasma phospholipids may be related to changes in body mass index, although findings remain inconsistent [61,62].
Human randomized trials that replace other fats with iTFA-rich partially hydrogenated oils confirm a systemic pro-inflammatory effect, validating that the effects of pure compounds translate when consumed as part of a complex food [63]. Two separate cross-sectional studies showed that iTFAs were associated with significantly high plasma inflammatory markers, such as TNFα, IL-6, C-reactive protein (CRP), and chemokine (C-C motif) ligand 2 (CCL2) in overweight women [64] and in cardiac patients [65]. In healthy men, a diet containing 8% of daily energy from iTFA increased CRP levels, whereas a soybean oil-based stick margarine-rich diet raised TNFα, IL-1β, and IL-6 production in the peripheral blood mononuclear cells of hypercholesterolemic subjects [9]. In CVD patients, TFAs levels correlated with parameters of oxidative stress, especially final lipid oxidation products [66]. Furthermore, a recent epidemiologic study has demonstrated a negative association between dietary trans-C18:1 (n-7) intake and adiposity, diabetes, and inflammation [67]. Despite this, due to limited long-term epidemiologic studies and the potential lipid-modifying effects of rTFAs at high doses, further controlled studies are needed to confirm their anti-inflammatory effects.
Chandra et al. [55] reported that both ruminant and industrial TFAs in plasma were associated with a favorable CVD risk profile; another study showed that in type 1 diabetes patients, higher all-C18:1trans isomers in erythrocyte membranes correlated with increased carotid plaques [68]. Notably, all-C18:1trans are prevalent TFAs found in partially hydrogenated vegetable oils and ruminant fats. Lechner et al. [69] found that naturally occurring trans-palmitoleic acid levels in heart failure patients were linked to a better cardiometabolic risk profile, whereas iTFAs were associated with dyslipidemia. In contrast, NHANES data showed that plasma TFAs, regardless of origin, were positively associated with elevated NT-proBNP, a biomarker of heart failure [70].
In type 2 diabetes, higher dairy intake increased trans-palmitoleic acid levels and correlated with TC and TG levels, but not with changes in body weight or metabolic control [71]. Yet, a meta-analysis on dairy fat intake found no association between circulating trans-palmitoleic acid and CVD incidence or mortality [72]. The observed differences between the findings may arise from dietary variations in the amount, confounding variables, or lack of harmonization between analytical methods for fatty acid determination in biological samples. Although comparative studies are limited, rTFAs are generally considered less harmful due to their lower dietary intake. Nevertheless, additional data are needed to clarify their respective roles in CVD and other metabolic disorders.
Table 2. Overview of recent studies assessing the link between TFAs and cardiovascular risk.
Table 2. Overview of recent studies assessing the link between TFAs and cardiovascular risk.
StudyStudy DesignStudy PopulationAssessment of TFAs IntakeAssessed CVD Risk Factors or OutcomesMain Findings
Riley et al., 2024 [31]Meta-analysisSubgroup analysis of 8 randomized controlled trials including 334 healthy or at-risk participants Intake of partially hydrogenated vegetable oilsLevels of Lp(a) Replacement of saturated fatty acids with TFAs led to a significant increase in Lp(a) levels.
Chandra et al., 2020 [55]Cross-sectional study3706 subjects from NorwayIntake assessed by plasma fatty acid compositionLipid profile, body mass index, systolic and diastolic blood pressureBoth ruminant and industrial TFAs levels in plasma were associated with favorable CVD risk profile.
Mesa et al., 2021 [68] Cross-sectional study167 patients with type 1 diabetes mellitus from SpainIntake assessed by fatty acids composition of erythrocyte membranesPresence of carotid plaquesPositive association between all-C18:1trans levels in the erythrocyte membranes and the presence of ≥3 carotid plaques.
Lechner et al., 2023 [69]Prospective cohort study404 patients with heart failure with preserved ejection fraction in Aldo-DHF trial from Germany and AustriaIntake assessed by whole blood fatty acid compositionCardiometabolic risk factors, aerobic capacity, and cardiac functionHigher levels of industrial TFAs were associated with increased LDL-C, TG, and HbA1c levels and lower aerobic capacity. Natural TFAs were inversely associated with cardiometabolic risk factors.
Wang et al., 2025 [70]Cross-sectional study1478 participants of the NHANES study from USIntake assessed by plasma fatty acid compositionLevels of NT-proBNP Higher levels of major TFAs in plasma (elaidic, vaccenic, and linolelaidic acids) and their sum were positively associated with elevated NT-proBNP.
Mitri et al., 2021 [71]Randomized clinical trial111 participants with type 2 diabetes mellitus from USIntake from dairy products Metabolic control, body weight, and CVD risk factorsIncreased dairy consumption was linked to higher trans-palmitoleic acid levels, which positively correlated with TC and TG levels.
Trieu et al., 2021 [72]Meta-analysisSubgroup analysis of 6 studies including 3477 participants Intake from dairy products CVD incidence and all-cause mortalityNo association between trans-palmitoleic acid levels and CVD risk and all-cause mortality.
Zhu et al., 2019 [73]Meta-analysis744,736 subjects from 24 studies Intake assessed by food frequency questionnaire, 7-day weighed food record or 24 h dietary recallCVD incidence or mortalityA positive dose–response association was found between dietary TFAs intake and CVD risk.
Ivey et al., 2023 [74]Prospective cohort study158,198 participants in the Million Veteran Program from USIntake assessed by food frequency questionnaire and estimated total fatty acid composition of commonly consumed oils and fats Atherosclerotic CVD event (ischemic heart disease, ischemic cerebrovascular disease, and peripheral artery disease) Higher intakes of monounsaturated TFAs and rumenic acid were linked to increased risks of ischemic heart disease and peripheral artery disease.
Zeinalabedini et al., 2024 [75]Case–control study 443 patients with ischemic heart disease and 453 controls from IranIntake assessed by food frequency questionnaireIschemic heart diseaseIntake of TFAs was not associated with ischemic heart disease.
Yao et al., 2021 [76] Prospective cohort study101,832 subjects from PLCO cancer screening trial from USIntake assessed by food frequency questionnaireAll-cause, CVD, and cancer mortality Dietary intake of TFAs was associated with all-cause mortality, but not with CVD and cancer mortality.
Abbreviations: TFAs, trans-fatty acids; CVD, cardiovascular disease; Lp(a), lipoprotein (a); LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; TC, total cholesterol; HbA1c, glycated hemoglobin; NT-proBNP, N-terminal pro B-type natriuretic peptide.
A meta-analysis by Zhu et al. [73] found a dose-dependent link between TFAs intake and CVD risk. A prospective study of the US veterans demonstrated that participants in the highest quintile of total monounsaturated TFAs intake had 13% higher CVD risk than those in the lowest quintile [74]. In contrast, a recent Iranian case–control study found no association between TFAs intake and ischemic heart disease [75], suggesting that substantial regional differences in TFAs consumption might affect their link with CVD. Increased TFAs consumption is thought to increase the risk of CVD mortality [77]. Yao et al. [76] found a modest association between TFAs intake and all-cause mortality, but no link with CVD or cancer mortality. Of note, these studies relied on food frequency questionnaires to estimate TFAs intake, which do not specify individual fatty acids and therefore could be affected by misclassification or inaccurate assessment. Analysis of randomized controlled trials and prospective studies showed a modest increase in mortality risk with TFAs intake [78]. Strong evidence supporting this hypothesis is provided by data from Denmark, where efforts to reduce iTFAs in food contributed to an 11% reduction in CVD mortality between 1991 and 2007 [79].
When evaluating the effects of TFAs under specific health conditions, such as CVD, obesity, or other metabolic disorders, it is important to distinguish between iTFA, rTFA, and those generated endogenously. These conditions involve distinct levels of free radical production and oxidative stress contributions to metabolism. This complexity makes it exceptionally difficult to discern the role of TFAs derived from “hidden industrial sources” from those derived from endogenous isomerization of natural cis fatty acids, caused by free radical species. Indeed, in humans, the literature indicates that oxidative stress can promote the formation of trans isomers from both MUFA and PUFA in cardiovascular and other diseases [21]. Consequently, measured TFA levels in human specimens (plasma, tissues) cannot be univocally attributed to dietary intakes alone, as discussed above. The contribution of endogenous TFAs, which are not obtained from the diet, can be identified by specific biomarkers, such as palmitelaidic acid [80].

4. Impact of Trans-Fatty Acids on Hepatic Steatosis, Fibrosis, and MASLD Progression

MASLD encompasses a wide variety of histopathological images, ranging from simple steatosis to inflammation, hepatic injury, fibrosis, end-stage hepatic disease, and hepatocellular carcinoma [81]. The multiple-hit theory describes the multifactorial pathogenesis of MASLD [82]. Dietary habits, genetic and epigenetic factors, obesity, insulin resistance, disturbed intestinal microbiota, adipocyte proliferation, adipocyte dysfunction, inflammation, oxidative stress, and mitochondrial dysfunction are all thought to participate cooperatively in the development and progression of MASLD [83].
Numerous animal studies have been conducted to elucidate the mechanisms by which TFAs are linked to MASLD, but previously published human studies are still limited. Therefore, it is crucial to highlight the magnitude of the outcome behind using TFAs, especially those industrially produced. Here, we highlight the possible principal links between TFAs and MASLD.

4.1. Modulation of Hepatic Lipid Metabolism by Trans-Fatty Acids

Hepatocyte TG content is affected by the balance between fatty acids input, which involves their uptake, synthesis, and esterification by liver cells, and output, which includes fatty acids oxidation and TG export [84]. In a comparative study on mice, TFAs intake was associated with increased hepatic TG, a key hallmark of MASLD, through the augmented stimulation of hepatic de novo lipogenesis and inhibition of hepatic lipolysis [85].
Mechanistic insights into the accumulation of TG in liver cells and TFA-induced hepatic steatosis often originate from reductionist models. For instance, treatment with pure elaidic acid upregulates key lipogenic enzymes, such as acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, and 3-hydroxy-2-methylglutaryl-CoA reductase, in hepatocytes and animal models, providing direct evidence of this pathway [86]. The physiological relevance of this mechanism is strengthened by studies using complex diets high in partially hydrogenated oils, which also result in hepatic TG accumulation, demonstrating that the lipogenic effect of industrial TFAs is robust enough to manifest within a complex food matrix [82]. Additionally, the inhibition of adipose triglyceride lipase (ATGL), the primary enzyme responsible for breaking down TG in the liver, further contributes to TG buildup [82]. Together, these mechanisms promote excessive fat storage within liver cells.
Additionally, insulin signaling pathways like insulin receptor substrate 1, Protein kinase C, and Ak strain transforming were suppressed in murine liver cells by TFAs, indicating hepatic insulin signaling impairment, which reflects insulin resistance and aggravates hepatic steatosis [87].

4.2. The Impact of Trans-Fatty Acids on Hepatic Oxidative Stress and Inflammation

Oxidative stress develops when the balance between reactive oxygen species (ROS) production and antioxidant defense is disrupted. Not only are TFAs linked to increased ROS production through impaired mitochondrial function or increased endoplasmic reticulum stress [88], but they also result in downregulated hepatic antioxidant enzymes such as peroxidase, thiobarbituric acid reactive substances, catalase, superoxide dismutase, and glutathione [89].
In addition, TFAs are robustly linked to increased hepatic inflammation [81], as reflected by hepatic NF-κB activation, high TNFα expression, osteopontin, CCl2, and macrophage markers [90]. Moreover, high liver IL-1β levels were linked to high iTFAs intake in mice [91]. Furthermore, in media containing TFAs compared to media with cis isomers, TNFα production was increased from the Kuffer Cells (KCs). So, this pathophysiological result can be explained partially by pro-inflammatory cytokine production and phagocytosis of macrophages and KCs [92].

4.3. Trans-Fatty Acids and Hepatic Fibrosis

Previous studies have linked iTFAs intake to the occurrence and progression of MASLD; however, the exact mechanism is unknown. An earlier study revealed that non-alcoholic steatohepatitis was induced by a high TFA diet [93]. This result was augmented by a comparative study in rats that were fed with different fatty diets and high-TFA diets, which induced more severe liver steatosis [94]. Similarly, compared to mice fed with cis and saturated fat diets, a TFA diet was associated with more advanced MASLD, high ALT, high hepatic TG and cholesterol levels, and increased expression of fibrosis-related genes [34], so the evidence for progression to fibrosis comes largely from animal models fed semi-purified diets spiked with specific iTFAs. These studies show that, in isolation, these compounds are sufficient to drive pro-fibrotic gene expression. Another animal study found that when TFAs were added to an atherogenic diet, it resulted in a more steatotic phenotype [94]. Moreover, a diet rich in TFAs endorses liver tumorigenesis, especially in HCV-infected mice. This could occur via the persistent stimulation of different inflammatory pathways [95].

4.4. Changes in Hepatic Function Induced by Trans-Fatty Acids

As observed in mice fed with TFAs, TFAs impair liver functions, which are indicators of hepatic injury [34,63,92]. Also, TFAs were linked to decreased microsomal triglyceride transfer protein (MTP) mRNA, leading to inadequate TG transfer to nascent ApoB particles. This led to a diminished VLDL secretion [88].

4.5. Human Studies Assessing the Link Between TFAs, MASLD, and Lipoproteins

As summarized in Table 3, a limited number of human studies have investigated the association between TFAs and MASLD.
While Lechner et al. [69] have mentioned an opposite association between plasma rTFAs and MASLD markers, Kratz et al. [98] referred to an improvement in glucose tolerance with dairy fat intake, possibly through reducing hepatic fat and improving liver and systemic insulin sensitivity. Regarding iTFAs, according to the Global Burden of Disease Data 2017, a major related risk factor of MASLD liver deaths was a high intake of TFAs [96]. Furthermore, a human study involving 4252 contributors showed a positive stepwise association between TFAs and the possibility of MASLD development. Higher TFA levels were associated with a worsened liver biochemical profile and an increased fatty liver index (FLI), indicating a higher possibility of MASLD and acceleration of its progression [97]. Additionally, a previous study demonstrated that TFAs were associated with high plasma levels of primary bile acids, which correlated with impaired cholesterol homeostasis [100]. MASLD patients had higher plasma eliadic acid levels, showed high fasting insulin, total cholesterol, and lower HDL-C, as well as higher hepatic TG content and a disturbed FA composition of hepatic and abdominal TG. They also exhibited considerably higher oxidative stress-related parameters in the liver [99]. The proposed mechanisms linking TFAs to dyslipidemia and MASLD are illustrated in Figure 2.
As noted above, an interpretation of TFAs’ effects in human studies on MASLD requires a clear distinction between iTFA, rTFA, and those endogenously formed. Given that MASLD patients exhibit enhanced oxidative stress, it becomes difficult to differentiate TFAs originating from industrial sources from those generated in vivo through free radical-driven isomerization of natural cis fatty acids. Consequently, TFAs levels measured in plasma cannot be attributed solely to dietary exposure.

5. The Issue of Hidden Trans-Fatty Acids and Food Labeling Regulations

Since the 1960s, the rising popularity of margarine and vegetable shortenings as cost-effective and healthier alternatives to animal lipids has resulted in estimated TFAs accounting for 2–3% of the total energy intake [7]. Due to their atherogenic potential, excessive intake of TFAs has been recognized as a significant and preventable factor in diet-related non-communicable diseases [101]. Therefore, over the past 20 years, different strategies have been applied to remove industrial TFAs from the food supply [102]. In 2010, the mean global intake was 1.4% of total energy intake [103], which exceeded the recommended limit of <1% of total energy intake [104]. According to the most recent epidemiological data, the global TFAs intake was below 0.3 to 4.2% of the total energy intake, indicating substantial reductions and the effectiveness of policies for reducing industrial TFAs [1].
In essence, “hidden TFAs” are industrially produced trans-fats that consumers unknowingly ingest because they are not clearly labeled as “trans-fat” due to regulatory loopholes, they are disguised under technical ingredient names like “partially hydrogenated oil”, or they are prevalent in foods that do not carry nutrition labels, such as restaurant meals, bakery items, and fried street foods. This “hidden” nature poses a critical public health challenge, as individuals trying to make healthy choices may still be consuming significant amounts of harmful iTFAs, contributing to dyslipidemia, cardiovascular disease, and MASLD without their knowledge. Several studies have reported that many foods, such as pastry [105] and cream-filled pastries [106], biscuits [107,108], savory baked goods [109], and fast foods (e.g., pizza, hot-dog, burger, fries, and pancakes) [10] exceeded regulatory TFA limits.
Despite the World Health Organization (WHO) setting the elimination of iTFAs from the global food supply as a priority by the end of 2025 [110], in some regions, challenges in this task still exist [111]. Although margarines were among the first successfully reformulated food products [11], a recent study reported that in Kazakhstan, margarine and spreads had on average more than 10% TFAs and that only 11% of these products, released in the market between 2018 and 2021, had less than 2% TFAs [112]. Also, a recent study has highlighted that two-thirds of branded soybean oils in Bangladesh exceeded the TFA limit [113]. On the contrary, although exposure to TFAs from edible oils in China is low, there is a recommendation that most consumed soybean oil should be replaced with other vegetable oils, such as safflower, sunflower, and rapeseed oil [114]. Among different food categories, fast food, canned and frozen products, and confectionery were identified as the major contributors to the TFAs in Egypt, the country with the highest TFAs intake [111]. Although data on the occurrence and estimated TFAs intake in Serbia are scarce, some previous studies have reported that processed foods, such as salami, wafers, tea biscuits, and snack products, can elevate the burden of trans-fat in diets, especially among young adults [115,116].
Regulatory approaches to reduce industrial-produced TFAs intake are based on mandatory labeling of TFAs, setting TFAs limits in the food products (2 g per 100 g of fat), and banning the use of partially hydrogenated oils. Due to the persistent presence of TFAs, particularly in processed and fried foods, continuous monitoring, mandatory regulatory measures, and public health education are needed to minimize the risk of further elevated iTFAs intake. Given the decline in the intake of iTFAs and the fact that rTFAs now serve as the primary dietary source of TFAs (accounting for 0.1 to 0.7% of energy intake) for over two-thirds of countries, it is important to promote dietary patterns that limit the consumption of full-fat dairy products and high-fat meats [1]. In addition to hidden TFAs that occur naturally in foods, awareness should be raised about the TFAs formed through traditional cooking methods and the monitoring of TFAs in non-prepackaged foods and trans-fat replacements [117].

6. Future Directions

Despite global progress in reducing dietary exposure to industrially produced TFAs, some regions need further support to implement national policies to eliminate these undesirable ingredients from the diet. In addition to enforcing stronger regional policies and monitoring TFAs in non-prepackaged and restaurant foods, nutritional education strategies should be used to raise public awareness on the risks of TFAs intake and the benefits of promoting healthy dietary choices. Considering the shift towards a plant-based diet and the importance of trans-fat replacements in the food industry, further research should focus on innovative technologies and the production of sustainable trans-fat substitutes and studying their long-term health effects.
To gain further insight into TFAs’ activities and health effects, robust and reliable methods for their assessment are of particular importance. Gas chromatography (GC) is the preferred method for analyzing TFAs’ profiles after their conversion to methyl esters by acid- or base-catalyzed reactions. Volatile TFA methyl ester can be detected using a flame ionization detector (FID) or a mass spectrometer (MS) [118]. Yet, different procedures for the optimization of chromatographic conditions and variable types of used detectors are the main factors that limit the comparison among the studies. Further, the same molecular mass and chemical structure of cis and trans fatty acids isomers require a high resolution for their precise chromatographic separation. The next analytical challenge in TFAs determination is the wide range of their concentrations. At present, GC–MS methods offer better analytical performance for accurate quantification. The most common method for TFAs determination in human blood was based on GC with non-specific FID, and the results are presented as a percentage of each detected fatty acid. Recently, a new isotope dilution–gas chromatography–negative chemical ionization–mass spectrometry method for the quantitation of four major TFAs in human blood was validated with an adequate sensitivity and specificity [119]. High-performance liquid chromatography techniques (HPLC) and capillary electrophoresis coupled with MS can also be used for TFAs profiling, but these methods have not reached significant usage in laboratory practice [120]. Future research should focus on the standardization of analytical protocols across laboratories, the improvement of the resolution for isomer separation, and the implementation of highly sensitive and specific MS-based approaches. Such methodological improvements are essential to ensure reliable inter-study comparability and to clarify the role of TFAs in lipoprotein metabolism, and consequently, their contribution to CVD risk and MASLD.
Future studies on the effects of TFAs on human health should go in two directions. One is to definitively resolve the old dilemmas regarding the specific role of industrial and ruminant TFAs. The other is to gain detailed insights into the effects of TFAs on specific lipid molecules and molecular pathways. Comprehensive answers to these questions might form the basis for the potential use of the serum levels of certain TFAs as non-invasive biomarkers of specific metabolic changes, or as a precision medicine tool for the prevention and risk management of cardiometabolic diseases. In line with this, emerging research suggests that TFAs may induce epigenetic modifications such as DNA methylation, which regulate gene expression in response to environmental factors, particularly diet. It has been demonstrated that elaidic acid affects DNA methylation in THP-1 cells, leading to the upregulation of pro-inflammatory genes and the suppression of anti-inflammatory genes [121]. In C57BL/6 mice, maternal elaidic acid intake increased DNA methylation in offspring adipose tissue [121]. These findings suggest that maternal TFAs consumption may induce epigenetic changes in offspring, potentially increasing the risk of metabolic disorders later in life [122]. TFAs may also modulate microRNA expression (miRNA) [123], and a TFA-rich diet alters HDL-associated miRNAs linked to lipid metabolism in healthy men [124]. However, most studies on TFA-induced epigenetic changes have been conducted in cell cultures or animal models, with limited clinical data available. Hence, future research is required to clarify the clinical significance of the observed epigenetic effects.
This review highlights the adverse effects of hidden TFAs on dyslipidemia, cardiovascular risk, and MASLD, emphasizing their impact on lipoprotein metabolism and hepatic lipogenesis. However, several limitations should be considered. Most evidence on TFAs and MASLD is derived from animal or cell studies, with few direct human clinical trials, which limits the generalizability of the findings to human populations. Many studies focus on labeled TFAs, but unlabeled or naturally occurring TFAs (e.g., from frying oils) are often overlooked, leading to a potential underestimation of actual intake. While regulatory progress has been made, inconsistent labeling results in TFAs remaining hidden and undeclared in many foods. Additionally, TFAs are frequently consumed alongside other unhealthy dietary components (e.g., sugars, refined carbohydrates), making it challenging to isolate their independent effects on dyslipidemia and MASLD. Finally, regional disparities in TFAs consumption further limit the universal applicability of the findings, as dietary habits, food regulations, and TFAs sources vary across countries.

7. Conclusions

TFAs in processed foods represent a significant public health concern due to their detrimental effects on lipid metabolism and their role in MASLD. Despite regulatory efforts to reduce iTFAs, their persistence in foods such as baked goods, fast food, and fried products continues to contribute to dyslipidemia, characterized by elevated LDL-C, triglycerides, and reduced HDL-C. Additionally, TFAs promote hepatic lipogenesis, oxidative stress, and inflammation, thereby accelerating the progression of MASLD to fibrosis and liver dysfunction. While rTFAs may have neutral or even beneficial metabolic effects, iTFAs are consistently linked to adverse health outcomes. Emerging evidence suggests that TFAs induce epigenetic modifications, influencing gene expression related to inflammation and lipid metabolism. However, most findings are derived from animal and cell studies, highlighting the need for further clinical research.

8. Recommendations

To mitigate risks, stronger global policies, improved food labeling, and public awareness campaigns are essential. Future research should focus on developing healthier fat alternatives and clarifying the long-term effects of TFAs substitutes. Addressing hidden TFAs in the diet is crucial for preventing metabolic disorders and improving liver and cardiovascular health worldwide by the following key strategies:
  • Strengthen regulations to eliminate iTFAs from processed and restaurant foods.
  • Enhance food labeling to improve consumer awareness of hidden TFAs.
  • Promote dietary education on the risks of TFAs and healthier fat alternatives.
  • Advance research on TFA-induced epigenetic changes and precision nutrition strategies.
By implementing these measures, the global burden of TFAs on metabolic health can be significantly reduced.

Author Contributions

Conceptualization, M.A.H.; methodology, J.V.; writing—original draft preparation, M.A.H., B.V., S.A., A.Z., A.S., J.V.; writing—review and editing, M.A.H., B.V., S.A., A.Z., A.S., J.V.; visualization, A.Z., M.A.H.; funding acquisition, B.V. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Acknowledgments

The authors from the University of Belgrade—Faculty of Pharmacy appreciate the support from the Ministry of Science, Technological Development and Innovation, Republic of Serbia (Grant Agreements with University of Belgrade—Faculty of Pharmacy No. 451-03-136/2025-03/200161 and No. 51-03-137/2025-03/200161).

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
TFAsTrans-fatty acids
MUFAsMonounsaturated fatty acids
PUFAsPolyunsaturated fatty acids
iTFAsIndustrially produced trans-fatty acids
rTFAsRuminant trans-fatty acids
CVDCardiovascular disease
MASLDMetabolic dysfunction-associated fatty liver disease
TCTotal cholesterol
LDL-CLow-density lipoprotein cholesterol
HDL-CHigh-density lipoprotein cholesterol
TGTriglycerides
CETPCholesteryl ester transfer protein
LCATLecithin-cholesterol acyltransferase
CRPC-reactive protein
ROSReactive oxygen species
FLIFatty liver index
GCGas chromatography
miRNAMicro RNA

References

  1. Wanders, A.J.; Zock, P.L.; Brouwer, I.A. Trans Fat Intake and Its Dietary Sources in General Populations Worldwide: A Systematic Review. Nutrients 2017, 9, 840. [Google Scholar] [CrossRef]
  2. Pietinen, P.; Ascherio, A.; Korhonen, P.; Hartman, A.M.; Willett, W.C.; Albanes, D.; Virtamo, J. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am. J. Epidemiol. 1997, 145, 876–887. [Google Scholar] [CrossRef]
  3. Oomen, C.M.; Ocke, M.C.; Feskens, E.J.; van Erp-Baart, M.A.; Kok, F.J.; Kromhout, D. Association between trans fatty acid intake and 10-year risk of coronary heart disease in the Zutphen Elderly Study: A prospective population-based study. Lancet 2001, 357, 746–751. [Google Scholar] [CrossRef]
  4. Mozaffarian, D.; Katan, M.B.; Ascherio, A.; Stampfer, M.J.; Willett, W.C. Trans fatty acids and cardiovascular disease. N. Engl. J. Med. 2006, 354, 1601–1613. [Google Scholar] [CrossRef]
  5. Brouwer, I.A.; Wanders, A.J.; Katan, M.B. Effect of animal and industrial trans fatty acids on HDL and LDL cholesterol levels in humans—A quantitative review. PLoS ONE 2010, 5, e9434, Erratum in PLoS ONE 2010, 5. [Google Scholar] [CrossRef]
  6. Jakobsen, M.U.; Overvad, K.; Dyerberg, J.; Heitmann, B.L. Intake of ruminant trans fatty acids and risk of coronary heart disease. Int. J. Epidemiol. 2008, 37, 173–182. [Google Scholar] [CrossRef] [PubMed]
  7. Willett, W.C.; Stampfer, M.J.; Manson, J.E.; Colditz, G.A.; Speizer, F.E.; Rosner, B.A.; Sampson, L.A.; Hennekens, C.H. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet 1993, 341, 581–585. [Google Scholar] [CrossRef]
  8. Nagpal, T.; Sahu, J.K.; Khare, S.K.; Bashir, K.; Jan, K. Trans fatty acids in food: A review on dietary intake, health impact, regulations and alternatives. J. Food Sci. 2021, 86, 5159–5174. [Google Scholar] [CrossRef] [PubMed]
  9. Oteng, A.B.; Kersten, S. Mechanisms of Action of trans Fatty Acids. Adv. Nutr. 2020, 11, 697–708. [Google Scholar] [CrossRef]
  10. Pipoyan, D.; Stepanyan, S.; Stepanyan, S.; Beglaryan, M.; Costantini, L.; Molinari, R.; Merendino, N. The Effect of Trans Fatty Acids on Human Health: Regulation and Consumption Patterns. Foods 2021, 10, 2452. [Google Scholar] [CrossRef]
  11. Bruce, J.H. Eliminating industrially produced trans fats from our diet-How well is it going? Nutr. Bull. 2023, 48, 427–434. [Google Scholar] [CrossRef]
  12. Dhaka, V.; Gulia, N.; Ahlawat, K.S.; Khatkar, B.S. Trans fats-sources, health risks and alternative approach—A review. J. Food Sci. Technol. 2011, 48, 534–541. [Google Scholar] [CrossRef]
  13. Silva, T.J.; Barrera-Arellano, D.; Ribeiro, A.P.B. Margarines: Historical approach, technological aspects, nutritional profile, and global trends. Food Res. Int. 2021, 147, 110486. [Google Scholar] [CrossRef] [PubMed]
  14. Mavlanov, U.; Czaja, T.P.; Nuriddinov, S.; Dalimova, D.; Dragsted, L.O.; Engelsen, S.B.; Khakimov, B. The effects of industrial processing and home cooking practices on trans-fatty acid profiles of vegetable oils. Food Chem. 2025, 469, 142571. [Google Scholar] [CrossRef]
  15. Manzoor, S.; Masoodi, F.A.; Rashid, R. Influence of food type, oil type and frying frequency on the formation of trans-fatty acids during repetitive deep-frying. Food Control 2023, 147, 109557. [Google Scholar] [CrossRef]
  16. Obi, J.; Furihata, K.; Sato, S.; Honda, M. Natural Sulfur Compounds, Allyl Isothiocyanate and Diallyl Disulfide, Promote Cis to Trans Isomerization of Fatty Acid Esters during Heat Treatment. J. Oleo Sci. 2023, 72, 881–887. [Google Scholar] [CrossRef]
  17. Hatem, O.; Kacar, O.F.; Kacar, H.K.; Szentpeteri, J.L.; Marosvolgyi, T.; Szabo, E. Trans isomeric fatty acids in human milk and their role in infant health and development. Front. Nutr. 2024, 11, 1379772. [Google Scholar] [CrossRef] [PubMed]
  18. Niwińska, B. Endogenous synthesis of rumenic acid in humans and cattle. J. Anim. Feed Sci. 2010, 19, 171–182. [Google Scholar] [CrossRef]
  19. Guillocheau, E.; Legrand, P.; Rioux, V. Trans-palmitoleic acid (trans-9-C16:1, or trans-C16:1 n-7): Nutritional impacts, metabolism, origin, compositional data, analytical methods and chemical synthesis. A review. Biochimie 2020, 169, 144–160. [Google Scholar] [CrossRef]
  20. Menounou, G.; Giacometti, G.; Scanferlato, R.; Dambruoso, P.; Sansone, A.; Tueros, I.; Amezaga, J.; Chatgilialoglu, C.; Ferreri, C. Trans Lipid Library: Synthesis of Docosahexaenoic Acid (DHA) Monotrans Isomers and Regioisomer Identification in DHA-Containing Supplements. Chem. Res. Toxicol. 2018, 31, 191–200. [Google Scholar] [CrossRef]
  21. Hung, W.L.; Hwang, L.S.; Shahidi, F.; Pan, M.H.; Wang, Y.; Ho, C.T. Endogenous formation of trans fatty acids: Health implications and potential dietary intervention. J. Funct. Foods 2016, 25, 14–24. [Google Scholar] [CrossRef]
  22. Chatgilialoglu, C.; Ferreri, C.; Melchiorre, M.; Sansone, A.; Torreggiani, A. Lipid geometrical isomerism: From chemistry to biology and diagnostics. Chem. Rev. 2014, 114, 255–284. [Google Scholar] [CrossRef]
  23. Devillard, E.; McIntosh, F.M.; Duncan, S.H.; Wallace, R.J. Metabolism of linoleic acid by human gut bacteria: Different routes for biosynthesis of conjugated linoleic acid. J. Bacteriol. 2007, 189, 2566–2570. [Google Scholar] [CrossRef] [PubMed]
  24. Banni, S.; Petroni, A.; Blasevich, M.; Carta, G.; Cordeddu, L.; Murru, E.; Melis, M.P.; Mahon, A.; Belury, M.A. Conjugated linoleic acids (CLA) as precursors of a distinct family of PUFA. Lipids 2004, 39, 1143–1146. [Google Scholar] [CrossRef]
  25. Vekic, J.; Stromsnes, K.; Mazzalai, S.; Zeljkovic, A.; Rizzo, M.; Gambini, J. Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk. Biomedicines 2023, 11, 2897. [Google Scholar] [CrossRef]
  26. Vekic, J.; Zeljkovic, A.; Al Rasadi, K.; Cesur, M.; Silva-Nunes, J.; Stoian, A.P.; Rizzo, M. A New Look at Novel Cardiovascular Risk Biomarkers: The Role of Atherogenic Lipoproteins and Innovative Antidiabetic Therapies. Metabolites 2022, 12, 108. [Google Scholar] [CrossRef] [PubMed]
  27. Vekic, J.; Stefanovic, A.; Zeljkovic, A. Obesity and Dyslipidemia: A Review of Current Evidence. Curr. Obes. Rep. 2023, 12, 207–222. [Google Scholar] [CrossRef]
  28. Schoeneck, M.; Iggman, D. The effects of foods on LDL cholesterol levels: A systematic review of the accumulated evidence from systematic reviews and meta-analyses of randomized controlled trials. Nutr. Metab. Cardiovasc. Dis. 2021, 31, 1325–1338. [Google Scholar] [CrossRef]
  29. Feingold, K.R. The Effect of Diet on Cardiovascular Disease and Lipid and Lipoprotein Levels. In Endotext; Feingold, K.R., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., Dungan, K., Hofland, J., et al., Eds.; MDText.com, Inc.: South Dartmouth, MA, USA, 2000. [Google Scholar]
  30. Islam, M.A.; Amin, M.N.; Siddiqui, S.A.; Hossain, M.P.; Sultana, F.; Kabir, M.R. Trans fatty acids and lipid profile: A serious risk factor to cardiovascular disease, cancer and diabetes. Diabetes Metab. Syndr. 2019, 13, 1643–1647. [Google Scholar] [CrossRef]
  31. Riley, T.M.; Sapp, P.A.; Kris-Etherton, P.M.; Petersen, K.S. Effects of saturated fatty acid consumption on lipoprotein (a): A systematic review and meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 2024, 120, 619–629. [Google Scholar] [CrossRef]
  32. Helgadottir, H.; Thorisdottir, B.; Gunnarsdottir, I.; Halldorsson, T.I.; Palsson, G.; Thorsdottir, I. Lower Intake of Saturated Fatty Acids Is Associated with Improved Lipid Profile in a 6-Year-Old Nationally Representative Population. Nutrients 2022, 14, 671. [Google Scholar] [CrossRef]
  33. Oteng, A.B.; Loregger, A.; van Weeghel, M.; Zelcer, N.; Kersten, S. Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease. Mol. Nutr. Food Res. 2019, 63, e1900385. [Google Scholar] [CrossRef]
  34. Izuddin, W.I.; Loh, T.C.; Nayan, N.; Akit, H.; Noor, A.M.; Foo, H.L. Blood lipid profiles, fatty acid deposition and expression of hepatic lipid and lipoprotein metabolism genes in laying hens fed palm oils, palm kernel oil, and soybean oil. Front. Vet. Sci. 2023, 10, 1192841. [Google Scholar] [CrossRef] [PubMed]
  35. Krogager, T.P.; Nielsen, L.V.; Kahveci, D.; Dyrlund, T.F.; Scavenius, C.; Sanggaard, K.W.; Enghild, J.J. Hepatocytes respond differently to major dietary trans fatty acid isomers, elaidic acid and trans-vaccenic acid. Proteome Sci. 2015, 13, 31. [Google Scholar] [CrossRef]
  36. Berriozabalgoitia, A.; Ruiz de Gordoa, J.C.; Amores, G.; Santamarina-Garcia, G.; Hernandez, I.; Virto, M. Normal-Fat vs. High-Fat Diets and Olive Oil vs. CLA-Rich Dairy Fat: A Comparative Study of Their Effects on Atherosclerosis in Male Golden Syrian Hamsters. Metabolites 2023, 13, 827. [Google Scholar] [CrossRef] [PubMed]
  37. Singh, V.P.; Fontaine, M.A.; Mangat, R.; Fouhse, J.M.; Diane, A.; Willing, B.P.; Proctor, S.D. High Vaccenic Acid Content in Beef Fat Attenuates High Fat and High Carbohydrate Western Diet Induced Changes in Lipid Metabolism and Gut Microbiota in Pigs. Microorganisms 2021, 9, 2517. [Google Scholar] [CrossRef] [PubMed]
  38. Reichard, J.F.; Haber, L.T. Mode-of-action evaluation for the effect of trans fatty acids on low-density lipoprotein cholesterol. Food Chem. Toxicol. 2016, 98, 282–294. [Google Scholar] [CrossRef]
  39. Sain, J.; Gonzalez, M.A.; Lavandera, J.V.; Scalerandi, M.V.; Bernal, C.A. The effects of trans-fatty acids on TAG regulation in mice depend on dietary unsaturated fatty acids. Br. J. Nutr. 2016, 116, 611–620. [Google Scholar] [CrossRef]
  40. Gengatharan, J.M.; Handzlik, M.K.; Chih, Z.Y.; Ruchhoeft, M.L.; Secrest, P.; Ashley, E.L.; Green, C.R.; Wallace, M.; Gordts, P.; Metallo, C.M. Altered sphingolipid biosynthetic flux and lipoprotein trafficking contribute to trans-fat-induced atherosclerosis. Cell Metab. 2025, 37, 274–290.e9. [Google Scholar] [CrossRef]
  41. Sarnyai, F.; Donko, M.B.; Matyasi, J.; Gor-Nagy, Z.; Marczi, I.; Simon-Szabo, L.; Zambo, V.; Somogyi, A.; Csizmadia, T.; Low, P.; et al. Cellular toxicity of dietary trans fatty acids and its correlation with ceramide and diglyceride accumulation. Food Chem. Toxicol. 2019, 124, 324–335. [Google Scholar] [CrossRef]
  42. Sarnyai, F.; Somogyi, A.; Gor-Nagy, Z.; Zambo, V.; Szelenyi, P.; Matyasi, J.; Simon-Szabo, L.; Kereszturi, E.; Toth, B.; Csala, M. Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides. Int. J. Mol. Sci. 2020, 21, 2626. [Google Scholar] [CrossRef] [PubMed]
  43. Kishi, S.; Fujiwara-Tani, R.; Luo, Y.; Kawahara, I.; Goto, K.; Fujii, K.; Ohmori, H.; Nakashima, C.; Sasaki, T.; Kuniyasu, H. Pro-metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts. Oncol. Lett. 2018, 15, 4423–4426. [Google Scholar] [CrossRef]
  44. Qiu, B.; Wang, Q.; Liu, W.; Xu, T.C.; Liu, L.N.; Zong, A.Z.; Jia, M.; Li, J.; Du, F.L. Biological effects of trans fatty acids and their possible roles in the lipid rafts in apoptosis regulation. Cell Biol. Int. 2018, 42, 904–912. [Google Scholar] [CrossRef] [PubMed]
  45. Aleksandrova, K.; Koelman, L.; Rodrigues, C.E. Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biol. 2021, 42, 101869. [Google Scholar] [CrossRef]
  46. Monguchi, T.; Hara, T.; Hasokawa, M.; Nakajima, H.; Mori, K.; Toh, R.; Irino, Y.; Ishida, T.; Hirata, K.I.; Shinohara, M. Excessive intake of trans fatty acid accelerates atherosclerosis through promoting inflammation and oxidative stress in a mouse model of hyperlipidemia. J. Cardiol. 2017, 70, 121–127. [Google Scholar] [CrossRef]
  47. Hirata, Y. trans-Fatty Acids as an Enhancer of Inflammation and Cell Death: Molecular Basis for Their Pathological Actions. Biol. Pharm. Bull. 2021, 44, 1349–1356. [Google Scholar] [CrossRef]
  48. Iwata, N.G.; Pham, M.; Rizzo, N.O.; Cheng, A.M.; Maloney, E.; Kim, F. Trans fatty acids induce vascular inflammation and reduce vascular nitric oxide production in endothelial cells. PLoS ONE 2011, 6, e29600. [Google Scholar] [CrossRef]
  49. Hirata, Y.; Inoue, A.; Suzuki, S.; Takahashi, M.; Matsui, R.; Kono, N.; Noguchi, T.; Matsuzawa, A. trans-Fatty acids facilitate DNA damage-induced apoptosis through the mitochondrial JNK-Sab-ROS positive feedback loop. Sci. Rep. 2020, 10, 2743. [Google Scholar] [CrossRef]
  50. Ma, W.W.; Zhao, L.; Yuan, L.H.; Yu, H.L.; Wang, H.; Gong, X.Y.; Wei, F.; Xiao, R. Elaidic acid induces cell apoptosis through induction of ROS accumulation and endoplasmic reticulum stress in SH-SY5Y cells. Mol. Med. Rep. 2017, 16, 9337–9346. [Google Scholar] [CrossRef]
  51. Lee, J.S.; Lim, J.N.; Wang, T.; Lee, S.B.; Hwang, J.H.; Jung, U.S.; Kim, M.J.; Choi, S.H.; Ishizuka, S.; Lee, H.G. Physiological concentrations of trans-11 18:1 vaccenic acid suppress pro-inflammatory markers under acute inflammation in isolated ICR mice splenocytes. Food Sci. Biotechnol. 2016, 25, 275–281. [Google Scholar] [CrossRef]
  52. Downs, S.M.; Bloem, M.Z.; Zheng, M.; Catterall, E.; Thomas, B.; Veerman, L.; Wu, J.H. The Impact of Policies to Reduce trans Fat Consumption: A Systematic Review of the Evidence. Curr. Dev. Nutr. 2017, 1, cdn-117. [Google Scholar] [CrossRef]
  53. Stender, S. Trans fat in foods in Iran, South-Eastern Europe, Caucasia and Central Asia: A market basket investigation. Food Policy 2020, 96, 101877. [Google Scholar] [CrossRef]
  54. Al-Jawaldeh, A.; Taktouk, M.; Chatila, A.; Naalbandian, S.; Abdollahi, Z.; Ajlan, B.; Al Hamad, N.; Alkhalaf, M.M.; Almamary, S.; Alobaid, R.; et al. A Systematic Review of Trans Fat Reduction Initiatives in the Eastern Mediterranean Region. Front. Nutr. 2021, 8, 771492. [Google Scholar] [CrossRef]
  55. Chandra, A.; Lyngbakken, M.N.; Eide, I.A.; Rosjo, H.; Vigen, T.; Ihle-Hansen, H.; Orstad, E.B.; Ronning, O.M.; Berge, T.; Schmidt, E.B.; et al. Plasma Trans Fatty Acid Levels, Cardiovascular Risk Factors and Lifestyle: Results from the Akershus Cardiac Examination 1950 Study. Nutrients 2020, 12, 1419. [Google Scholar] [CrossRef]
  56. Guggisberg, D.; Burton-Pimentel, K.J.; Walther, B.; Badertscher, R.; Blaser, C.; Portmann, R.; Schmid, A.; Radtke, T.; Saner, H.; Fournier, N.; et al. Molecular effects of the consumption of margarine and butter varying in trans fat composition: A parallel human intervention study. Lipids Health Dis. 2022, 21, 74. [Google Scholar] [CrossRef]
  57. Verneque, B.J.F.; Machado, A.M.; de Abreu Silva, L.; Lopes, A.C.S.; Duarte, C.K. Ruminant and industrial trans-fatty acids consumption and cardiometabolic risk markers: A systematic review. Crit. Rev. Food Sci. Nutr. 2022, 62, 2050–2060. [Google Scholar] [CrossRef] [PubMed]
  58. Iino, T.; Toh, R.; Nagao, M.; Shinohara, M.; Harada, A.; Murakami, K.; Irino, Y.; Nishimori, M.; Yoshikawa, S.; Seto, Y.; et al. Effects of Elaidic Acid on HDL Cholesterol Uptake Capacity. Nutrients 2021, 13, 3112. [Google Scholar] [CrossRef] [PubMed]
  59. Mendivil, E.J.; Barcenas-Rivera, G.; Ramos-Lopez, O.; Hernandez-Guerrero, C.; Rivera-Iniguez, I.; Perez-Beltran, Y.E. Interaction of CETP rs708272 Polymorphism on Trans Fatty Acid Intake and Glucose Metabolism Markers. Nutrients 2024, 16, 3683. [Google Scholar] [CrossRef]
  60. Gupta, R.; Abraham, R.A.; Kondal, D.; Dhatwalia, S.; Jeemon, P.; Reddy, K.S.; Prabhakaran, D.; Ramakrishnan, L. Association of trans fatty acids with lipids and other cardiovascular risk factors in an Indian industrial population. BMC Res. Notes 2019, 12, 342. [Google Scholar] [CrossRef]
  61. Hastert, T.A.; de Oliveira Otto, M.C.; Le-Scherban, F.; Steffen, B.T.; Steffen, L.M.; Tsai, M.Y.; Jacobs, D.R., Jr.; Baylin, A. Association of plasma phospholipid polyunsaturated and trans fatty acids with body mass index: Results from the Multi-Ethnic Study of Atherosclerosis. Int. J. Obes. 2018, 42, 433–440. [Google Scholar] [CrossRef]
  62. Del Pozo, M.D.P.; Lope, V.; Criado-Navarro, I.; Pastor-Barriuso, R.; Fernandez de Larrea, N.; Ruiz, E.; Castello, A.; Lucas, P.; Sierra, A.; Romieu, I.; et al. Serum Phospholipid Fatty Acids Levels, Anthropometric Variables and Adiposity in Spanish Premenopausal Women. Nutrients 2020, 12, 1895. [Google Scholar] [CrossRef]
  63. Baer, D.J.; Judd, J.T.; Clevidence, B.A.; Tracy, R.P. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: A randomized crossover study. Am. J. Clin. Nutr. 2004, 79, 969–973. [Google Scholar] [CrossRef] [PubMed]
  64. Lopez-Garcia, E.; Schulze, M.B.; Meigs, J.B.; Manson, J.E.; Rifai, N.; Stampfer, M.J.; Willett, W.C.; Hu, F.B. Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J. Nutr. 2005, 135, 562–566. [Google Scholar] [CrossRef]
  65. Mozaffarian, D.; Rimm, E.B.; King, I.B.; Lawler, R.L.; McDonald, G.B.; Levy, W.C. trans fatty acids and systemic inflammation in heart failure. Am. J. Clin. Nutr. 2004, 80, 1521–1525. [Google Scholar] [CrossRef]
  66. Hadj Ahmed, S.; Kharroubi, W.; Kaoubaa, N.; Zarrouk, A.; Batbout, F.; Gamra, H.; Najjar, M.F.; Lizard, G.; Hininger-Favier, I.; Hammami, M. Correlation of trans fatty acids with the severity of coronary artery disease lesions. Lipids Health Dis. 2018, 17, 52. [Google Scholar] [CrossRef]
  67. Pranger, I.G.; Muskiet, F.A.J.; Kema, I.P.; Singh-Povel, C.; Bakker, S.J.L. Potential Biomarkers for Fat from Dairy and Fish and Their Association with Cardiovascular Risk Factors: Cross-sectional Data from the LifeLines Biobank and Cohort Study. Nutrients 2019, 11, 1099. [Google Scholar] [CrossRef]
  68. Mesa, A.; Cofan, M.; Esmatjes, E.; Perea, V.; Boswell, L.; Gimenez, M.; Sala-Vila, A.; Vinagre, I.; Vinals, C.; Chiva-Blanch, G.; et al. Biomarkers of fatty acid intake are independently associated with preclinical atherosclerosis in individuals with type 1 diabetes. Eur. J. Nutr. 2021, 60, 4595–4605. [Google Scholar] [CrossRef]
  69. Lechner, K.; Bock, M.; von Schacky, C.; Scherr, J.; Lorenz, E.; Lechner, B.; Haller, B.; Krannich, A.; Halle, M.; Wachter, R.; et al. Trans-fatty acid blood levels of industrial but not natural origin are associated with cardiovascular risk factors in patients with HFpEF: A secondary analysis of the Aldo-DHF trial. Clin. Res. Cardiol. 2023, 112, 1541–1554. [Google Scholar] [CrossRef]
  70. Wang, X.; Chen, X.; Jiang, F.; Cheng, Y.; Li, Y. Circulating trans fatty acids are related to serum levels of NT-proBNP in general population. Int. J. Cardiol. 2025, 422, 132974. [Google Scholar] [CrossRef]
  71. Mitri, J.; Tomah, S.; Furtado, J.; Tasabehji, M.W.; Hamdy, O. Plasma Free Fatty Acids and Metabolic Effect in Type 2 Diabetes, an Ancillary Study from a Randomized Clinical Trial. Nutrients 2021, 13, 1145. [Google Scholar] [CrossRef]
  72. Trieu, K.; Bhat, S.; Dai, Z.; Leander, K.; Gigante, B.; Qian, F.; Korat, A.V.A.; Sun, Q.; Pan, X.F.; Laguzzi, F.; et al. Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis. PLoS Med. 2021, 18, e1003763. [Google Scholar] [CrossRef]
  73. Zhu, Y.; Bo, Y.; Liu, Y. Dietary total fat, fatty acids intake, and risk of cardiovascular disease: A dose-response meta-analysis of cohort studies. Lipids Health Dis. 2019, 18, 91. [Google Scholar] [CrossRef]
  74. Ivey, K.L.; Nguyen, X.T.; Li, R.; Furtado, J.; Cho, K.; Gaziano, J.M.; Hu, F.B.; Willett, W.C.; Wilson, P.W.; Djousse, L. Association of dietary fatty acids with the risk of atherosclerotic cardiovascular disease in a prospective cohort of United States veterans. Am. J. Clin. Nutr. 2023, 118, 763–772. [Google Scholar] [CrossRef]
  75. Zeinalabedini, M.; Ladaninezhad, M.; Mobarakeh, K.A.; Hoshiar-Rad, A.; Shekari, S.; Askarpour, S.A.; Ardekanizadeh, N.H.; Esmaeili, M.; Abdollahi, M.; Doaei, S.; et al. Association of dietary fats with ischemic heart disease (IHD): A case-control study. J. Health Popul. Nutr. 2024, 43, 19, Erratum in J. Health Popul. Nutr. 2024, 43, 51. [Google Scholar] [CrossRef]
  76. Yao, X.; Xu, X.; Wang, S.; Xia, D. Associations of Dietary Fat Intake with Mortality From All Causes, Cardiovascular Disease, and Cancer: A Prospective Study. Front. Nutr. 2021, 8, 701430. [Google Scholar] [CrossRef]
  77. Huang, N.K.; Buzkova, P.; Matthan, N.R.; Djousse, L.; Hirsch, C.H.; Kizer, J.R.; Longstreth, W.T., Jr.; Mukamal, K.J.; Lichtenstein, A.H. Associations of Serum Nonesterified Fatty Acids with Coronary Heart Disease Mortality and Nonfatal Myocardial Infarction: The CHS (Cardiovascular Health Study) Cohort. J. Am. Heart Assoc. 2021, 10, e019135. [Google Scholar] [CrossRef]
  78. Jayedi, A.; Soltani, S.; Emadi, A.; Ghods, K.; Shab-Bidar, S. Dietary intake, biomarkers and supplementation of fatty acids and risk of coronary events: A systematic review and dose-response meta-analysis of randomized controlled trials and prospective observational studies. Crit. Rev. Food Sci. Nutr. 2024, 64, 12363–12382. [Google Scholar] [CrossRef]
  79. Bjoernsbo, K.S.; Joensen, A.M.; Joergensen, T.; Lundbye-Christensen, S.; Bysted, A.; Christensen, T.; Fagt, S.; Capewell, S.; O’Flaherty, M. Quantifying benefits of the Danish transfat ban for coronary heart disease mortality 1991–2007: Socioeconomic analysis using the IMPACTsec model. PLoS ONE 2022, 17, e0272744. [Google Scholar] [CrossRef]
  80. Sansone, A.; Tolika, E.; Louka, M.; Sunda, V.; Deplano, S.; Melchiorre, M.; Anagnostopoulos, D.; Chatgilialoglu, C.; Formisano, C.; Di Micco, R.; et al. Hexadecenoic Fatty Acid Isomers in Human Blood Lipids and Their Relevance for the Interpretation of Lipidomic Profiles. PLoS ONE 2016, 11, e0152378. [Google Scholar] [CrossRef]
  81. Kechagias, S.; Nasr, P.; Blomdahl, J.; Ekstedt, M. Established and emerging factors affecting the progression of nonalcoholic fatty liver disease. Metabolism 2020, 111, 154183. [Google Scholar] [CrossRef]
  82. Li, Y.; Yang, P.; Ye, J.; Xu, Q.; Wu, J.; Wang, Y. Updated mechanisms of MASLD pathogenesis. Lipids Health Dis. 2024, 23, 117. [Google Scholar] [CrossRef]
  83. Buzzetti, E.; Pinzani, M.; Tsochatzis, E.A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 2016, 65, 1038–1048. [Google Scholar] [CrossRef]
  84. Nguyen, P.; Leray, V.; Diez, M.; Serisier, S.; Le Bloc’h, J.; Siliart, B.; Dumon, H. Liver lipid metabolism. J. Anim. Physiol. Anim. Nutr. 2008, 92, 272–283. [Google Scholar] [CrossRef]
  85. Kawano, Y.; Cohen, D.E. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease. J. Gastroenterol. 2013, 48, 434–441. [Google Scholar] [CrossRef]
  86. Shao, F.; Ford, D.A. Elaidic acid increases hepatic lipogenesis by mediating sterol regulatory element binding protein-1c activity in HuH-7 cells. Lipids 2014, 49, 403–413. [Google Scholar] [CrossRef]
  87. Zhao, X.; Shen, C.; Zhu, H.; Wang, C.; Liu, X.; Sun, X.; Han, S.; Wang, P.; Dong, Z.; Ma, X.; et al. Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway. Molecules 2016, 21, 705. [Google Scholar] [CrossRef]
  88. Machado, R.M.; Stefano, J.T.; Oliveira, C.P.; Mello, E.S.; Ferreira, F.D.; Nunes, V.S.; de Lima, V.M.; Quintao, E.C.; Catanozi, S.; Nakandakare, E.R.; et al. Intake of trans fatty acids causes nonalcoholic steatohepatitis and reduces adipose tissue fat content. J. Nutr. 2010, 140, 1127–1132. [Google Scholar] [CrossRef]
  89. Ismail, H.; Mubashar, Z.; Khan, H.; Naveed, Z.; Dilshad, E.; Bhatti, M.Z.; Anwaar, S.; Saleem, S.; Mehmood, S.; Rahman, A.; et al. Effects of a High Trans Fatty Acid Diet on Kidney-, Liver-, and Heart-Associated Diseases in a Rabbit Model. Metabolites 2024, 14, 442. [Google Scholar] [CrossRef]
  90. Afonso, M.S.; Lavrador, M.S.; Koike, M.K.; Cintra, D.E.; Ferreira, F.D.; Nunes, V.S.; Castilho, G.; Gioielli, L.A.; Paula Bombo, R.; Catanozi, S.; et al. Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation. J. Nutr. Biochem. 2016, 32, 91–100, Erratum in J. Nutr. Biochem. 2016, 36, 89–90. [Google Scholar] [CrossRef]
  91. Koppe, S.W.; Elias, M.; Moseley, R.H.; Green, R.M. Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 297, G378–G384. [Google Scholar] [CrossRef]
  92. Obara, N.; Fukushima, K.; Ueno, Y.; Wakui, Y.; Kimura, O.; Tamai, K.; Kakazu, E.; Inoue, J.; Kondo, Y.; Ogawa, N.; et al. Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice. J. Hepatol. 2010, 53, 326–334. [Google Scholar] [CrossRef]
  93. Trevaskis, J.L.; Griffin, P.S.; Wittmer, C.; Neuschwander-Tetri, B.A.; Brunt, E.M.; Dolman, C.S.; Erickson, M.R.; Napora, J.; Parkes, D.G.; Roth, J.D. Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 302, G762–G772. [Google Scholar] [CrossRef]
  94. Daniels, S.J.; Leeming, D.J.; Detlefsen, S.; Bruun, M.F.; Hjuler, S.T.; Henriksen, K.; Hein, P.; Krag, A.; Karsdal, M.A.; Nielsen, M.J.; et al. Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 318, G410–G418. [Google Scholar] [CrossRef]
  95. Hu, X.; Wang, X.; Jia, F.; Tanaka, N.; Kimura, T.; Nakajima, T.; Sato, Y.; Moriya, K.; Koike, K.; Gonzalez, F.J.; et al. A trans-fatty acid-rich diet promotes liver tumorigenesis in HCV core gene transgenic mice. Carcinogenesis 2020, 41, 159–170. [Google Scholar] [CrossRef]
  96. Paik, J.M.; Mir, S.; Alqahtani, S.A.; Younossi, Y.; Ong, J.P.; Younossi, Z.M. Dietary Risks for Liver Mortality in NAFLD: Global Burden of Disease Data. Hepatol. Commun. 2022, 6, 90–100. [Google Scholar] [CrossRef]
  97. Mazidi, M.; Katsiki, N.; Mikhailidis, D.P.; Banach, M. Link between plasma trans-fatty acid and fatty liver is moderated by adiposity. Int. J. Cardiol. 2018, 272, 316–322. [Google Scholar] [CrossRef]
  98. Kratz, M.; Marcovina, S.; Nelson, J.E.; Yeh, M.M.; Kowdley, K.V.; Callahan, H.S.; Song, X.; Di, C.; Utzschneider, K.M. Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not beta-cell function in humans. Am. J. Clin. Nutr. 2014, 99, 1385–1396. [Google Scholar] [CrossRef]
  99. Araya, J.; Rodrigo, R.; Videla, L.A.; Thielemann, L.; Orellana, M.; Pettinelli, P.; Poniachik, J. Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin. Sci. 2004, 106, 635–643. [Google Scholar] [CrossRef]
  100. Byrd, D.A.; Sinha, R.; Weinstein, S.J.; Albanes, D.; Freedman, N.D.; Sampson, J.; Loftfield, E. An investigation of cross-sectional associations of a priori-selected dietary components with circulating bile acids. Am. J. Clin. Nutr. 2021, 114, 1802–1813. [Google Scholar] [CrossRef]
  101. Kontis, V.; Cobb, L.K.; Mathers, C.D.; Frieden, T.R.; Ezzati, M.; Danaei, G. Three Public Health Interventions Could Save 94 Million Lives in 25 Years. Circulation 2019, 140, 715–725. [Google Scholar] [CrossRef]
  102. Steele, L.; Drummond, E.; Nishida, C.; Yamamoto, R.; Branca, F.; Parsons Perez, C.; Allemandi, L.; Arnanz, L.; Schoj, V.; Khanchandani, H.S.; et al. Ending Trans Fat-The First-Ever Global Elimination Program for a Noncommunicable Disease Risk Factor: JACC International. J. Am. Coll. Cardiol. 2024, 84, 663–674. [Google Scholar] [CrossRef]
  103. Micha, R.; Khatibzadeh, S.; Shi, P.; Fahimi, S.; Lim, S.; Andrews, K.G.; Engell, R.E.; Powles, J.; Ezzati, M.; Mozaffarian, D.; et al. Global, regional, and national consumption levels of dietary fats and oils in 1990 and 2010: A systematic analysis including 266 country-specific nutrition surveys. BMJ 2014, 348, g2272, Erratum in BMJ 2015, 350, h1702. [Google Scholar] [CrossRef]
  104. Nishida, C.; Uauy, R. WHO Scientific Update on health consequences of trans fatty acids: Introduction. Eur. J. Clin. Nutr. 2009, 63 (Suppl. S2), S1–S4. [Google Scholar] [CrossRef]
  105. Żbikowska, A.; Onacik-Gür, S.; Kowalska, M.; Rutkowska, J. trans Fatty Acids in Polish Pastry. J. Food Prot. 2019, 82, 1028–1033. [Google Scholar] [CrossRef]
  106. Torabi, P.; Moraffah, F.; Amini, M.; Pourjabar, Z.; Kargar, S.; Hajimahmoodi, M. Fatty acid composition of Iranian sweetened confectionery creams, with an emphasis on trans fatty acids. J. Food Compos. Anal. 2022, 105, 104153. [Google Scholar] [CrossRef]
  107. Zupanic, N.; Hribar, M.; Hristov, H.; Lavrisa, Z.; Kusar, A.; Gregoric, M.; Blaznik, U.; Korousic Seljak, B.; Golja, P.; Vidrih, R.; et al. Dietary Intake of trans Fatty Acids in the Slovenian Population. Nutrients 2021, 13, 207. [Google Scholar] [CrossRef]
  108. Aued-Pimentel, S.; Kus-Yamashita, M.M.M. Analysis of the fat profile of industrialized food in Brazil with emphasis on trans-fatty acids. J. Food Compos. Anal. 2021, 97, 103799. [Google Scholar] [CrossRef]
  109. Marakis, G.; Fotakis, C.; Tsigarida, E.; Mila, S.; Palilis, L.; Skoulika, S.; Petropoulos, G.; Papaioannou, A.; Proestos, C. Fatty acid profile of processed foods in Greece with focus on trans fatty acids. J. Consum. Prot. Food Saf. 2020, 15, 373–381. [Google Scholar] [CrossRef]
  110. WHO. Replace Trans Fat by 2023: An Action Package to Eliminate Industrially-Produced Trans Fat from the Global Food Supply; World Health Organization: Geneva, Switzerland, 2018. [Google Scholar]
  111. Ismail, G.; Abo El Naga, R.; El Sayed Zaki, M.; Jabbour, J.; Al-Jawaldeh, A. Analysis of Fat Content with Special Emphasis on Trans Isomers in Frequently Consumed Food Products in Egypt: The First Steps in the Trans Fatty Acid Elimination Roadmap. Nutrients 2021, 13, 3087. [Google Scholar] [CrossRef]
  112. Toshtay, K.; Auyezov, A.; Azat, S.; Busquets, R. Trans fatty acids and saturated fatty acids in margarines and spreads in Kazakhstan: Study period 2015–2021. Food Chem. X 2025, 25, 102246. [Google Scholar] [CrossRef]
  113. Sarwar, S.; Shaheen, N.; Ashraf, M.M.; Bahar, N.; Akter, F.; Hossain, M.M.; Mridha, M.K.; Kajal, M.A.M.; Rasul, S.S.B.; Khondker, R.; et al. Fatty acid profile emphasizing trans-fatty acids in commercially available soybean and palm oils and its probable intake in Bangladesh. Food Chem. Adv. 2024, 4, 100611. [Google Scholar] [CrossRef]
  114. Fang, H.; Cao, M.; Zhang, X.; Wang, K.; Deng, T.; Lin, J.; Liu, R.; Wang, X.; Liu, A. The assessment of trans fatty acid composition in edible oil of different brands and regions in China in 2021. J. Food Compos. Anal. 2023, 121, 105394. [Google Scholar] [CrossRef]
  115. Timic, J.B.; Duricic, I.D.; Ristic-Medic, D.K.; Sobajic, S. Fatty acid composition including trans-fatty acids in salty snack food from the Serbian market. J. Serbian Chem. Soc. 2018, 83, 685–698. [Google Scholar] [CrossRef]
  116. Ristic-Medic, D.; Petrovic, S.; Polak, T.; Bertoncelj, J.; Arsic, A.; Takic, M.; Vucic, V.; Gurinovic, M.; Korosec, M. Trans fatty acids in frequently consumed products from Serbian and Slovenian market. Cent. Eur. J. Public Health 2022, 30, 51–57. [Google Scholar] [CrossRef]
  117. Ghebreyesus, T.A.; Frieden, T.R. REPLACE: A roadmap to make the world trans fat free by 2023. Lancet 2018, 391, 1978–1980. [Google Scholar] [CrossRef]
  118. Ratnayake, W.M. Overview of methods for the determination of trans fatty acids by gas chromatography, silver-ion thin-layer chromatography, silver-ion liquid chromatography, and gas chromatography/mass spectrometry. J. AOAC Int. 2004, 87, 523–539. [Google Scholar]
  119. Kuiper, H.C.; Wei, N.; McGunigale, S.L.; Vesper, H.W. Quantitation of trans-fatty acids in human blood via isotope dilution-gas chromatography-negative chemical ionization-mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2018, 1076, 35–43. [Google Scholar] [CrossRef]
  120. Bystricka, Z.; Durackova, Z. Gas chromatography determination of fatty acids in the human erythrocyte membranes—A review. Prostaglandins Leukot. Essent. Fat. Acids 2016, 115, 35–40. [Google Scholar] [CrossRef]
  121. Flores-Sierra, J.; Arredondo-Guerrero, M.; Cervantes-Paz, B.; Rodriguez-Rios, D.; Alvarado-Caudillo, Y.; Nielsen, F.C.; Wrobel, K.; Wrobel, K.; Zaina, S.; Lund, G. The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo. Lipids Health Dis. 2016, 15, 75. [Google Scholar] [CrossRef]
  122. Zeljkovic, A.; Vekic, J.; Stefanovic, A. Obesity and dyslipidemia in early life: Impact on cardiometabolic risk. Metabolism 2024, 156, 155919. [Google Scholar] [CrossRef] [PubMed]
  123. Molnar, R.; Szabo, L.; Tomesz, A.; Deutsch, A.; Darago, R.; Ghodratollah, N.; Varjas, T.; Nemeth, B.; Budan, F.; Kiss, I. In vivo effects of olive oil and trans-fatty acids on miR-134, miR-132, miR-124-1, miR-9-3 and mTORC1 gene expression in a DMBA-treated mouse model. PLoS ONE 2021, 16, e0246022. [Google Scholar] [CrossRef] [PubMed]
  124. Desgagne, V.; Guerin, R.; Guay, S.P.; Corbin, F.; Couture, P.; Lamarche, B.; Bouchard, L. Changes in high-density lipoprotein-carried miRNA contribution to the plasmatic pool after consumption of dietary trans fat in healthy men. Epigenomics 2017, 9, 669–688. [Google Scholar] [CrossRef] [PubMed]
Ijms 26 11715 g001
Figure 1. Putative mechanisms of TFAs’ effects on lipid metabolism (* data from in vitro studies; # data from animal studies).
Figure 1. Putative mechanisms of TFAs’ effects on lipid metabolism (* data from in vitro studies; # data from animal studies).
Ijms 26 11715 g001
Ijms 26 11715 g002
Figure 2. Proposed mechanisms linking TFAs to dyslipidemia and MASLD. Mechanistic pathways through which TFAs contribute to dyslipidemia and MASLD. Industrial TFAs promote hepatic lipid accumulation, oxidative stress, and inflammation, driving MASLD progression. Ruminant TFAs may have neutral or protective effects.
Figure 2. Proposed mechanisms linking TFAs to dyslipidemia and MASLD. Mechanistic pathways through which TFAs contribute to dyslipidemia and MASLD. Industrial TFAs promote hepatic lipid accumulation, oxidative stress, and inflammation, driving MASLD progression. Ruminant TFAs may have neutral or protective effects.
Ijms 26 11715 g002
Table 1. Structures and origin of the most studied TFAs.
Table 1. Structures and origin of the most studied TFAs.
Name StructureOrigin
Elaidic acidC18:1n-9tIndustrial TFA
Linoelaidic acidC18:2n-6ttIndustrial TFA
Palmitelaidic acid C16:1n-7tRuminant TFA
Vaccenic acidC18:1n-7tRuminant TFA
Rumenic acidC18:2n-9c, 11tRuminant TFA
Table 3. Overview of studies assessing the link between TFAs, MASLD, and lipoproteins.
Table 3. Overview of studies assessing the link between TFAs, MASLD, and lipoproteins.
StudyStudy DesignStudy PopulationSource of TFAsAssessment of MASLDMain Findings
Lechner et al., 2023 [69] Cohort study404 heart failure patients with preserved ejection fraction (HFpEF) have a mean age of 67 years, with 52% being femaleNaturally occurring and iTFAsLiver enzymes (ALT and GGT)Plasma naturally occurring TFAs were inversely associated with dyslipidemia, BMI, MASLD markers, and inflammation.
iTFAs were positively associated with dyslipidemia and dysglycemia.
Paik et al., 2022 [96]Data collected from the 2017 GBD (global population-level retrospective study)Population-level retrospective risk–outcome analysis (using Global Burden of Disease data)All sources, including ruminant products and partially hydrogenated vegetable oilsVariable due to the different countries where the data are collectedMASLD liver deaths were 2.3 per 100,000 (2017) and correlated with a high intake of sugar-sweetened beverages, red meat, TFAs, and a low intake of nuts/seeds and milk, IKF, increased BMI, FG, and BP.
Mazidi et al., 2018 [97]Cross-sectional studyA total of 4252 participants, comprising 46.4% men. The mean age was 50.6 yearsiTFAsLiver tests and FLIPositive significant associations between TFA levels and the possibility of MASLD determined by FLI, liver tests, and BMI.
Kratz et al., 2014 [98]Cross-sectional study17 patients with MASLD and 15 controls matched for age and BMINaturally occurring TFAsBy either liver biopsy within only the past 3 years or elevated liver enzymes combined with fatty liver by US or CT after other causes of liver dysfunction were excludedDairy fat, including naturally occurring TFAs, was in inverse association with FG and hepatic fat content, while it had a positive association with systemic and liver insulin sensitivity.
Araya et al., 2004 [99]Cohort study30 patients with a BMI of 45.6 ± 8.3 kg/m2 and with age range of 39–45 years, who had voluntary therapeutic gastroplasty or gastrectomy. The control group consisted of those who underwent voluntary anti-reflux surgeryiTFAsHaematoxylin/eosin-stained liver sectionsMASLD patients exhibited a significantly high elaidic acid level, were significantly more obese, and had higher fasting insulin levels, higher plasma TC, lower HDL-cholesterol levels, higher hepatic TG content, a disturbed FA composition in hepatic and abdominal TG, and a higher lipid peroxidation index.
Abbreviations: TFAs, trans-fatty acids; HFpEF, heart failure patients with preserved ejection fraction; ALT, alanine-aminotransferase; GGT, gamma-glutamyl transferase; BMI, body mass index; MASLD, metabolic dysfunction-associated fatty liver disease; iTFAs, industrial TFAs; GBD, Global Burden of Disease; IKF, impaired kidney function; FG, fasting glucose; BP, blood pressure; FLI, fatty liver index; US, ultrasonography; CT, computed tomography; TC, total cholesterol; TG: triglycerides.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Hegazy, M.A.; Vidovic, B.; Abobakr, S.; Zeljkovic, A.; Stefanovic, A.; Vekic, J. Hidden Industrial Trans-Fatty Acids: Mechanistic Insights into Dyslipidemia, Cardiovascular Disease, and Metabolic Dysfunction-Associated Steatotic Liver Disease. Int. J. Mol. Sci. 2025, 26, 11715. https://doi.org/10.3390/ijms262311715

AMA Style

Hegazy MA, Vidovic B, Abobakr S, Zeljkovic A, Stefanovic A, Vekic J. Hidden Industrial Trans-Fatty Acids: Mechanistic Insights into Dyslipidemia, Cardiovascular Disease, and Metabolic Dysfunction-Associated Steatotic Liver Disease. International Journal of Molecular Sciences. 2025; 26(23):11715. https://doi.org/10.3390/ijms262311715

Chicago/Turabian Style

Hegazy, Mona A, Bojana Vidovic, Shimaa Abobakr, Aleksandra Zeljkovic, Aleksandra Stefanovic, and Jelena Vekic. 2025. "Hidden Industrial Trans-Fatty Acids: Mechanistic Insights into Dyslipidemia, Cardiovascular Disease, and Metabolic Dysfunction-Associated Steatotic Liver Disease" International Journal of Molecular Sciences 26, no. 23: 11715. https://doi.org/10.3390/ijms262311715

APA Style

Hegazy, M. A., Vidovic, B., Abobakr, S., Zeljkovic, A., Stefanovic, A., & Vekic, J. (2025). Hidden Industrial Trans-Fatty Acids: Mechanistic Insights into Dyslipidemia, Cardiovascular Disease, and Metabolic Dysfunction-Associated Steatotic Liver Disease. International Journal of Molecular Sciences, 26(23), 11715. https://doi.org/10.3390/ijms262311715

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop