[Suppression effect of secoisolariciresinol diglucoside against trans fatty acids-induced oxidative damage and inflammatory in brain of offspring mice].

OBJECTIVE: To probe into the protective effect of different dose of secoisolariciresinol diglucoside(SDG) on brain of offspring of mice anainst oxidative damage and inflammatory reaction induced by maternal exposure to trans fatty acids(TFA) during gestation, and observe the the changes of regulating Nrf2/Keap1 pathway in the course. METHODS: 30 healthy female mice(C57BL/6) were divided into 5 groups randomly, they are respectively control group, TFA-exposed group, and three SDG-intervention groups(low-(TFA+LSDG), medium-(TFA+MSDG) and high-(TFA+HSDG)). The pregnancy mice of control group and TFA group were treated with distilled water and 60 mg/kg·d TFA by gavage, in the same time, the mice of three SDG-intervention groups were treated with 60 mg/kg·d TFA by gavage and fed with feed included SDG(10, 20 and 30 mg/kg). The treatment to pregnancy mice continued to birth of offspring. After 21 days of lactation, the offspring were killed under anesthesia and the experiment was ended. The coefficient of brain was calculated. The levels of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), malondialdehyde(MDA), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ) and amyloid-ß(Aß)of brain were detected. RT-PCR and Western Blot was used to detected gene expression and protein levels of nuclear factor erythroid-2 related factor 2(Nrf2), kelch-like ECH-associated protein 1(Keap1), quinone oxidoreductase 1(NQO1) and hemeoxygenase-l(HO-1). RESULTS: Compared with control group, the brain coefficient and Aß1-40 of offspring of TFA-group had no significant changes(P>0.05), the activity of SOD and GSH-Px reduced, the content of MDA, IFN-γ, TNF-α and Aß1-42 increased, the level of mRNA and protein expression of Nrf2, NQO1 and HO-1 decreased and the level of mRNA and protein expression of Keap1 increase because of the exposion to TFA during gestation and all the differences were statistically significant(P<0.05). Compared with TFA-group, the brain coefficient, Aß1-40 and the level of NQO1 mRNA of offspring of three SDG-intervention groups had no significant changes(P>0.05), the activity of SOD(the middle and high dose SDG intervention groups) and GSH-Px(three SDG-intervention groups) increased, the content of MDA(the middle and high dose SDG intervention groups), IFN-γ(the middle and high dose SDG intervention groups), TNF-α(three SDG-intervention groups) and Aß1-42(the middle and high dose SDG intervention groups) decreased, the mRNA expression of Nrf2 and HO-1(the middle and high dose SDG intervention groups) was up-regulated, the mRNA expression of Keap1(the middle and high dose SDG intervention group) decreased, proteic expression of Nrf2, NQO1 and HO-1 of three SDG-intervention groups increase and the level of protein of Keap1 decreased because of the intervention of SDG during gestation(P<0.05). CONCLUSION: These result suggest that maternal TFA exposure during gestation can result in oxidative stress and inflammation to brain of offspring in a way. SDG can protect brain of mice of offspring from TFA-induced oxidative injury by up-regulating the expression of mRNA and protein of Nrf2, down-regulating the expression of Keap1, accelerating expression of protein of NQO1 and HO-1 which are antioxidant protein lying downstream of pathway of Nrf2/Keap1.

Ending Trans Fat-The First-Ever Global Elimination Program for a Noncommunicable Disease Risk Factor: JACC International.

Industrially produced trans fat (iTFA) is a harmful compound created as a substitute for animal and saturated fats. Estimated to cause up to 500,000 deaths per year, it is replaceable. In 2018, Resolve to Save Lives, the World Health Organization (WHO), Global Health Advocacy Incubator, and NCD Alliance partnered to achieve global trans fat elimination. The WHO Director-General called for the elimination of trans fat by 2023 through best practice policies outlined in the WHO REPLACE package. Since the accelerated global efforts in 2018, 43 countries have adopted best practice regulations protecting an additional 3.2 billion people and building momentum toward global elimination. Current coverage will prevent 66% of deaths estimated to be caused each year by trans fat in foods. Despite producing and selling iTFA-free products in many countries, companies continue to sell iTFA-containing products in unregulated markets. Global incentives, accountability mechanisms, and regional policies will help achieve the elimination goal.

The Lipid-Heart Hypothesis and the Keys Equation Defined the Dietary Guidelines but Ignored the Impact of Trans-Fat and High Linoleic Acid Consumption.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (ΔChol.) from the consumption of saturated fat (ΔS), polyunsaturated fat (ΔP), and cholesterol (ΔZ): ΔChol. = 1.2(2ΔS - ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

Disability and costs of IHD attributable to the consumption of trans-fatty acids in Brazil.

OBJECTIVE: To estimate the disability and costs of the Brazilian Unified Health System for IHD attributable to trans-fatty acid (TFA) consumption in 2019. DESIGN: This ecological study used secondary data from the Global Burden of Disease (GBD) Study 2019 to estimate the years lived with disability from IHD attributable to TFA in Brazil in 2019. Data on direct costs (purchasing power parity: 1 Int$ = R$ 2·280) were obtained from the Hospital and Ambulatory Information Systems of the Brazilian Unified Health System. Moreover, the total costs in each state were divided by the resident population in 2019 and multiplied by 10 000 inhabitants. The relationship between the socio-demographic index, disease and economic burden was investigated. SETTING: Brazil and its twenty-seven states. PARTICIPANTS: Adults aged ≥ 25 years of both sexes. RESULTS: IHD attributable to TFA consumption resulted in 11 165 years lived with disability (95 % uncertainty interval 932­18 462) in 2019 in Brazil. A total of Int$ 54 546 227 (95 % uncertainty interval 4 505 792­85 561 810) was spent in the Brazilian Unified Health System in 2019 due to IHD attributable to TFA, with the highest costs of hospitalisations, for males and individuals aged ≥ 50 years or over. The highest costs were observed in Sergipe (Int$ 6508/10 000; 95 % uncertainty interval 576­10 265), followed by the two states from the South. Overall, as the socio-demographic index increases, expenditures increase. CONCLUSIONS: TFA consumption results in a high disease and economic IHD burden in Brazil, reinforcing the need for more effective health policies, such as industrial TFA elimination, following the international agenda.

Encapsulation of conjugated linoleic acid and ruminant trans fatty acids to study the prevention of metabolic syndrome-a review.

Studies have reported the potential benefits of consuming conjugated linoleic acid (CLA) and ruminant trans fatty acids (R-TFAs) in reducing the risk factors of metabolic syndrome (MetS). In addition, encapsulation of CLA and R-TFAs may improve their oral delivery and further decrease the risk factors of MetS. The objectives of this review were (1) to discuss the advantages of encapsulation; (2) to compare the materials and techniques used for encapsulating CLA and R-TFAs; and (3) to review the effects of encapsulated vs non-encapsulated CLA and R-TFAs on MetS risk factors. Examination of papers citing micro- and nano-encapsulation methods used in food sciences, as well as the effects of encapsulated vs non-encapsulated CLA and R-TFAs, was conducted using the PubMed database. A total of 84 papers were examined; of these, 18 studies were selected that contained information on the effects of encapsulated CLA and R-TFAs. The 18 studies that described encapsulation of CLA or R-TFAs indicated that micro- or nano-encapsulation processes stabilized CLA and prevented oxidation. CLA was mainly encapsulated using carbohydrates or proteins. So far, oil-in-water emulsification followed by spray-drying were the frequently used techniques for encapsulation of CLA. Further, 4 studies investigated the effects of encapsulated CLA on MetS risk factors compared with non-encapsulated CLA. A limited number of studies investigated the encapsulation of R-TFAs. The effects of encapsulated CLA or R-TFAs on the risk factors for MetS remain understudied; thus, additional studies comparing the effects of encapsulated and non-encapsulated CLA or R-TFAs are needed.

A prospective cohort study on the association between dietary fatty acids intake and risk of hypertension incident.

There are inconclusive results available on the association between dietary fatty acid intake and the risk of hypertension (HTN) incident. In this study, we investigate the relationship between baseline dietary fatty acids intake including polyunsaturated fatty acid (PUFA), trans fatty acids (TFA), monounsaturated fatty acid (MUFA), and saturated fatty acid (SFA), and the risk of first incidence hypertension. The current prospective cohort study was carried out from the Ravansar Non-Communicable Diseases (RaNCD) cohort. A food frequency questionnaire (FFQ) with 118 items was used for the assessment of dietary data. Cox proportional hazards analyses were done to estimate hazard ratios (HR) and 95% confidence intervals (CIs) of the highest versus lowest quartile intake of SFA, PUFA, MUFA, and SFA and risk of HTN. Out of 7359 eligible participants, 597 new cases of HTN were identified over an average of 6.4 ± 1.33 years of follow-up. No significant relationship was observed between the fourth compared to the first categories of dietary SFA (HR: 0.82, 95% CI 0.55, 1.21; P trend: 0.476), MUFA (HR: 0.71, 95% CI 0.48, 1.06; P trend: 0.252), PUFA (HR: 0.86, 95% CI 0.62, 1.19; P trend: 0.315) and TFA (HR: 0.99, 95% CI 0.76, 1.27; P trend: 0.675), and risk of HTN. However, a significant inverse association between each 1 g per day increase in dietary MUFA intake during 6.4 years of follow up and HTN incident (HR: 0.97; 95% CI 0.94, 0.99; P 0.044) was observed. In brief, our study revealed that higher dietary MUFA intake was protectively associated with HTN incident. Dietary MUFA-rich foods should be encouraged to improve blood pressure.

Burden of ischemic heart disease attributable to trans fatty acids, 1990-2019.

BACKGROUND & AIM: The impact of cardiovascular disease attributable to trans fatty acids (TFAs) in the Brazilian population has not been systematically evaluated. This study aims to analyze the burden of ischemic heart disease (IHD) attributable to TFAs in Brazil between 1990 and 2019. METHODS: Data from the Global Burden of Disease Study 2019 were used to investigate the attributable burden in Brazil and its 27 federative units, for both sexes-pooled adults aged ≥25 years. Mortality and disability-adjusted life years (DALYs) from IHD attributable to TFAs were expressed as crude and age-standardized rates and differences from 1990 to 2019 by percentage and annualized rate of change. Linear regression was used to investigate trends. National voluntary and regulatory policies for industrial TFAs (iTFAs) implemented until 2019, summary exposure value (SEV) and sociodemographic index (SDI) were examined. RESULTS: Between 1990 and 2019, crude and age-standardized mortality rates from IHD attributable to TFAs decreased by -15.9% and -58.0%, respectively, in Brazil. A decrease in crude (-23.3%) and age-standardized (-56.4%) DALY rates of IHD attributable to TFAs was also noticed in the country. States of the South, Southeast, and the Federal District had the largest declines of IHD attributable to TFAs, while states of the Northeast and North had the smallest or even an increase. The policies already adopted had little effect on the IHD burden. A lower SEV and higher SDI value seemed to reduce the burden of IHD. CONCLUSIONS: Although a downward trend in IHD attributable to TFAs and a reduction in exposure to TFAs were observed, this burden is still relevant in Brazil, reinforcing the importance of diet policies, such as banning iTFAs.

Association of dietary fatty acids with the risk of atherosclerotic cardiovascular disease in a prospective cohort of United States veterans.

BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVDs) are the leading cause of worldwide adult mortality. Although broad classes of dietary fats have been shown to alter ASCVD risk, the roles that individual dietary fatty acids play in influencing ASCVD risk are unclear. OBJECTIVES: The aim of this prospective cohort study was to examine the relationships of the total fat classes and individual fatty acids with the risk of ASCVD. METHODS: The Million Veteran Program is a prospective cohort whereby dietary intake of fatty acids was assessed in 158,198 participants that had enrolled between January 2011 and November 2018 and were free of ASCVD at baseline. Incident ASCVD was ascertained from the Veterans Affairs electronic health records and the National Death Index. Multivariable-adjusted hazard ratios (HRs) for the relationship between fat intake and ASCVD risk were computed using Cox regression models. RESULTS: The mean age was 61 years, 88% were males. A total of 11,771 ASCVD events were identified during the follow-up. When compared with the lowest quintile, participants in the highest quintile of dietary trans-monounsaturated fats and conjugated linoleic acids had an increased risk (HR [95% CI]) of ASCVD events: 1.10 (1.04, 1.17) and 1.11 (1.05, 1.18), respectively. When compared with low consumers, participants in the highest quintile of total cis-polyunsaturated fatty acid intake had a lower risk of experiencing an ASCVD event 0.93 (0.87, 0.99). CONCLUSION: Although higher intakes of specific trans-fatty acids and conjugated linoleic were associated with an increased risk of ASCVD, the same cannot be said for all other fat classes. This work suggests that care must be taken when drawing general conclusions regarding the health effects of dietary individual fatty acids.

C57bl/6 Mice Show Equivalent Taste Preferences toward Ruminant and Industrial Trans Fatty Acids.

Two distinct types of trans fatty acids (TFA) are found in the diet. Industrial TFA such as elaidic acid (EA) have deleterious effects on metabolic risk factors, and oppositely ruminant TFA including trans-palmitoleic acid (TPA) may have beneficial effects. The objective is to evaluate the taste preference between EA, TPA, lecithin or water. In this study, 24 female C57BL/6 mice were microchipped and placed in two separate IntelliCages®. Nano encapsulated TFA or lecithin were added to drinking water in different corners of the cage with normal diet. The study was carried out over 5 weeks, during which mice were exposed to water only (weeks 1 and 3), TFA or lecithin (week 2), and EA or TPA (weeks 4 and 5). Mice weights, corner visits, nose pokes (NP), and lick number were measured each week. The results demonstrated that mice consume more TFA, either EA or TPA, compared with lecithin. In addition, the mice licked more EA compared with TPA in one cage; conversely, in the other cage they licked more TPA compared with EA. However, when TFA positions were swapped, mice had equal licks for EA and TPA. In sum, mice preferred TFA, in equal matter compared with controls; therefore, the results demonstrate the potential for TFA-type substitution in diet.

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.

BACKGROUND: Industrially processed trans-fatty acids (IP-TFA) have been linked to altered lipoprotein metabolism, inflammation and increased NT-proBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown. METHODS: This is a secondary analysis of the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were: 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e' 7.1 ± 1.5; NT-proBNP 158 ng/L (IQR 82-298). A principal component analysis was conducted but not used for further analysis as cumulative variance for the first two PCs was low. Spearman's correlation coefficients as well as linear regression analyses, using sex and age as covariates, were used to describe associations of whole blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF and neurohumoral activation at baseline and after 12 months. RESULTS: Blood levels of the naturally occurring TFA C16:1n-7t were inversely associated with dyslipidemia, body mass index/truncal adiposity, surrogate markers for non-alcoholic fatty liver disease and inflammation at baseline/12 months. Conversely, IP-TFA C18:1n9t, C18:2n6tt and C18:2n6tc were positively associated with dyslipidemia and isomer C18:2n6ct with dysglycemia. C18:2n6tt and C18:2n6ct were inversely associated with submaximal aerobic capacity at baseline/12 months. No significant association was found between TFA and cardiac function. CONCLUSIONS: In HFpEF patients, higher blood levels of IP-TFA, but not naturally occurring TFA, were associated with dyslipidemia, dysglycemia and lower functional capacity. Blood TFAs, in particular C16:1n-7t, warrant further investigation as prognostic markers in HFpEF. Higher blood levels of industrially processed TFA, but not of the naturally occurring TFA C16:1n-7t, are associated with a higher risk cardiometabolic phenotype and prognostic of lower aerobic capacity in patients with HFpEF.

Ultra-Processed Food Consumption Is Related to Higher Trans Fatty Acids, Sugar Intake, and Micronutrient-Impaired Status in Schoolchildren of Bahia, Brazil.

Ultra-processed food (UPF) consumption impacts nutrient intake and plays an important role in non-communicable diseases (NCD), even among schoolchildren. This cross-sectional study aimed to characterize the food consumption of this population and its relationship with laboratory and anthropometric aspects. A sample of 190 subjects aged 5 to 19 y was randomly selected for dietary, laboratory, and anthropometric assessment. Statistical inference was calculated using Spearman's correlation. Excess weight was observed in 34%, a high Waist-to-Height Ratio in 9%, and hypertriglyceridemia in 17% of the subjects, higher among those from urban schools (45%, p = 0.011; 15%, p = 0.015; 24%, p = 0.026, respectively). UPF consumption represented 21% of caloric intake and showed a positive correlation with trans fatty acids (r = 0.70) and sugar (r = 0.59) intake. Unprocessed food consumption showed a weak, but significant, correlation with Body Mass Index (r = 0.22) and Waist Circumference (r = 0.23), while processed meat showed a negative correlation with serum ferritin (r = -0.16) and vitamins D (r = -0.20) and B12 (r = -0.15). These findings highlight the need for public policies to promote Food and Nutritional Security for schoolchildren to prevent NCD and nutritional deficiencies.

Different Types of Industry-Produced and Ruminant Trans Fatty Acid Intake and Risk of Type 2 Diabetes: Findings From the NutriNet-Santé Prospective Cohort.

OBJECTIVE: The deleterious effects of trans fatty acids (TFAs) on cardiovascular health are well established; however, their impact on type 2 diabetes remains poorly understood. In particular, little is known about the impact of specific TFA types on type 2 diabetes etiology. We aimed to explore the associations between different types of TFAs (total, ruminant, industry produced [iTFAs], and corresponding specific isomers) and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 105,551 participants age >18 years from the French NutriNet-Santé cohort (2009-2021) were included (mean baseline age 42.7 years; SD 14.6 years); 79.2% were women. Dietary intake data, including usual TFA intake, were collected using repeated 24-h dietary records (n = 5.7; SD 3.1). Associations between sex-specific quartile of dietary TFAs and diabetes risk were assessed using multivariable Cox models. RESULTS: Total TFA intake was associated with higher type 2 diabetes risk (hazard ratio [HR]quartile 4 vs. 1 1.38; 95% CI 1.11-1.73; Ptrend < 0.001; n = 969 incident cases). This association, specifically observed for iTFAs (HR 1.45; 95% CI 1.15-1.83; Ptrend < 0.001), was mainly driven by elaidic acid (HR 1.37; 95% CI 1.09-1.72; Ptrend < 0.001) and linolelaidic acid (HR 1.29; 95% CI 1.04-1.58; Ptrend = 0.07). In contrast, ruminant TFAs were not significantly associated with risk of type 2 diabetes. CONCLUSIONS: In this large prospective cohort, higher intakes of total and iTFAs were associated with increased type 2 diabetes risk. These findings support the World Health Organization's recommendation to eliminate iTFAs from the food supply worldwide. Consumers should be advised to limit the consumption of food products containing partially hydrogenated oils (main vector of iTFAs). This may contribute to lowering the substantial global burden of type 2 diabetes.

Development and application of the TFA macrosimulation model: a case study of modelling the impact of trans fatty acid (TFA) elimination policies in Brazil.

INTRODUCTION: The consumption of trans-fatty acids (TFA) is directly associated with cardiovascular disease risk and is responsible for a significant health burden globally. The policy strategies for reducing TFA include limiting their content in foods and eliminating partially hydrogenated oils (PHO) in the market. This study aims to describe a comparative risk assessment macrosimulation model and to apply this tool to estimate the potential reductions in CVD mortality gained from the compared scenarios of TFA reduction/elimination in Brazil. METHODOLOGY: We developed and implemented a comparative risk assessment macrosimulation model estimates the potential CVD mortality reduction (coronary heart disease - CHD- and stroke) if TFA intake is reduced in diets. The TFA macrosimulation model estimates the change in the annual number of NCD deaths between baseline with current TFA consumption levels and alternate or counterfactual scenarios, such as considering different limits to TFA content in foods and the elimination of PHO in Brazil in 2018. The model incorporated additional outputs related to other impacts of TFA reduction on DPP, such as Years of Life Lost, Years of Productive Life Lost, and related economic impacts of premature deaths. RESULTS: In 2018, a 2% limit for TFA in the oils and fats and a 5% limit of TFAs for other foods could avert or postpone approximately 2,000 deaths (UI 95% 1,899-2,142) and save US$ 32.1 million savings in productivity losses to the economy associated to premature deaths. An intermediate scenario, applying a 2% limit of TFA in all food products In Brazil could prevent or postpone approximately 6,300 deaths (UI 95% 5,925-6,684) and the premature deaths prevented would represent US$ 100.2 million in economic saving. Finally, by banning PHO, approximately 10,500 deaths could be prevented or postponed (UI 95% 9,963 - 10,909), corresponding to US$ 166.7 million in savings to the economy because of premature deaths. CONCLUSION: The TFA macrosimulation model can efficiently compare different policy scenarios for trans fats reduction policies at the country level and proves that the elimination of PHOs from the food market in Brazil may significantly reduce the health burden of trans fatty acids in the country compared to other policy options. The model also represents a useful public health tool to support TFA reduction and elimination policies in other countries.

Dietary Ruminant and Industrial Trans-Fatty Acids Intake and Colorectal Cancer Risk.

As colorectal cancer (CRC) is largely due to modifiable lifestyle habits, the awareness on its risk factors is highly important. Dietary fatty acids have been linked to CRC risk. We explored the association between dietary trans fatty acids (TFAs) intake and CRC risk. We analyzed 865 CRC cases (434 in colon and 404 in rectum) and 3206 controls of the IROPICAN study, with data collected by trained interviewers using validated questionnaires. TFAs intake (industrial and ruminant types) was categorized into quartiles. Multivariate logistic regression models were built to calculate the odds ratios (OR) for the association between CRC and TFAs. We observed a positive association between industrial TFAs and colon cancer (OR for highest vs lowest quartile [ORQ4vsQ1] = 1.28, 95% confidence interval 1.07-1.54). A higher association was observed between industrial TFAs and CRC, occurring after 50 years of age. In addition, elaidic acid was associated with an increased risk of colon (ORQ4vsQ1 = 1.58, 1.24-2.02) and specifically of proximal colon cancer (OR Q4vsQ1 = 2.12, 1.40-3.20), as well as of rectum cancer (ORQ4vsQ1 = 1.40, 1.07-1.83). An inverse association was observed between ruminant TFAs intake and colon cancer risk (ORQ4vsQ1 = 0.80, 0.67-0.97). Industrial TFAs, such as semisolid/solid hydrogenated oils, may increase the risk of CRC, especially colon and proximal colon cancer. In contrast, ruminant TFAs do not appear to be associated with CRC. Awareness programs and regulatory actions regarding hydrogenated oils are warranted, given their high consumption through ultra-processed foods in more developed and less developed countries.