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.

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.

Understanding the Complexities of Eliminating Trans Fatty Acids: The Case of the Trans Fatty Acid Ban in Thailand.

Trans fatty acids (TFAs) have no known health benefits and are linked to an increased risk of noncommunicable diseases (NCDs). To eliminate TFAs from the food supply, the government of Thailand imposed a ban on partially hydrogenated oils (PHOs) in 2018. This study was aimed at analyzing the government policies and actions to eliminate TFAs in Thailand, focusing on policy content, context, process, and actors. This single-case qualitative study used a documentary review and interviews with 20 key policy actors. The data analysis was guided by thematic analysis based on the policy triangle framework. The results reveal that policy actors-government organizations, academics, civil society organizations, and the food industry-have different roles, interests, and influences with regard to eliminating TFAs in Thailand. Both formal and informal communication among policy actors aided in the policymaking process and the actions that followed. Changing perceptions of TFAs, the low intake of PHOs in Thailand, hype around trans fats, and trade dynamics shaped the government's decision to impose the ban. As a result, the ban was selected to avoid the technical components of TFA elimination. This study suggests that eliminating TFAs in Thailand could be further enhanced by strengthening government actions in terms of enforcement and creating consumer awareness.

Pre-pregnancy fat intake in relation to hypertensive disorders of pregnancy.

BACKGROUND: Many studies have linked intakes of fat and of specific fatty acids during pregnancy with preeclampsia; however, information on the association of intake before pregnancy with hypertensive disorders of pregnancy (HDP) is scant. OBJECTIVES: We evaluated the associations of intakes of major and specific types of fat before pregnancy with the risks of HDP, including preeclampsia and gestational hypertension (GHTN). METHODS: We followed 11,535 women without chronic disease participating in the Nurses' Health Study II from 1991 and 2009. Pre-pregnancy dietary fat was assessed by an FFQ. Intakes of total fat, saturated fat, trans fatty acid (TFA), MUFAs, PUFAs, and fat subtypes (omega-3 and omega-6) were categorized into quintiles of intake. HDP were self-reported. The RRs (95% CIs) of HDP were estimated by log-binomial generalized estimating equation regression models, with an exchangeable correlation matrix to account for repeated pregnancies while adjusting for potential confounders. RESULTS: During 19 years of follow-up, there were 495 cases of preeclampsia (2.9%) and 561 (3.3%) cases of GHTN in 16,892 singleton pregnancies. The mean age at pregnancy was 34.6 years (SD, 3.9 years). Among major fat types, only pre-pregnancy TFA was related to a higher risk of HDP (RR, 1.32; 95% CI: 1.05-1.66), and only for preeclampsia (RR, 1.50; 95% CI: 1.07-2.10) but not for GHTN (RR, 1.21; 95% CI: 0.87-1.70). Among specific types of PUFAs, intake of arachidonic acid was positively related with GHTN (RR, 1.43; 95% CI: 1.00-2.04) but not preeclampsia (RR, 1.08; 95% CI: 0.75-1.57). In analyses restricted to pregnancies 1 year after the diet assessment, women with the highest intake of long-chain omega-3 fatty acids had a 31% lower risk of HDP (95% CI: 3%-51%), which was driven by preeclampsia (RR, 0.55; 95% CI: 0.33-0.92). CONCLUSIONS: Pre-pregnancy intakes of total fat, saturated fat, and MUFA were unrelated to HDP, whereas TFA was positively related to HDP. These findings highlight the importance of ongoing efforts to eliminate TFA from the global food supply.

Influence of Heating during Cooking on Trans Fatty Acid Content of Edible Oils: A Systematic Review and Meta-Analysis.

Consumption of trans fatty acids (TFA) is associated with adverse health outcomes and is a considerable burden on morbidity and mortality globally. TFA may be generated by common cooking practices and hence contribute to daily dietary intake. We performed a systematic review and meta-analysis to investigate the relationship between heating edible oils and change in their TFA content. A systematic search of experimental studies investigating the effect of various methods of heating on TFA content of edible oils was conducted in Medline and Embase since their inception up to 1 October 2020 without language restrictions. Comparable data were analysed using mixed multilevel linear models taking into account individual study variation. Thirty-three studies encompassing twenty-one different oils were included in this review. Overall, heating to temperatures <200 °C had no appreciable impact on different TFA levels. Between 200 and 240 °C, levels of C18:2 t (0.05% increase per 10 °C rise in temperature, 95% CI: 0.02 to 0.05%), C18:3t (0.18%, 95% CI: 0.14 to 0.21%), and total TFA (0.38%, 95% CI: 0.20 to 0.55%) increased with temperature. A further increase in total TFA was observed with prolonged heating between 200 and 240 °C. Our findings suggest that heating edible oils to common cooking temperatures (≤200 °C) has minimal effect on TFA generation whereas heating to higher temperatures can increase TFA level. This provides further evidence in favour of public health advice that heating oils to very high temperatures and prolonged heating of oils should be avoided.

The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels.

The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels [...].

Palm Oil Processing and Controversies over Its Health Effect: Overview of Positive and Negative Consequences.

Palm oil is the world's most commonly used vegetable oil and extracted both from fruit and seed of palm tree. However, its high saturated fatty acid content raised controversies over consumption of the oil. Few scientific findings suggest it as a risk factor for cardiovascular disease and increased consumer's awareness over healthy diet raised claim over it. So that, this article aimed to review literatures on palm oil extraction process and its positive and negative health consequences and besides suggest strategies for healthy diet. Literature search of relevant articles was conducted by using Google scholar, PubMed, Web of science, MEDLINE, World Health Organization library online catalogue, UNICEF library, Open access thesis and dissertations published between 2009 and 2021 explored. Study reports recommend that palmitic acid from vegetable source has less effect on blood total cholesterol and low density lipoprotein cholesterol level as compared to palmitic acid from animal source. In contrary tocotrienols of palm oil lowers blood bad cholesterol level by 7-38%. Moreover, palm oil triacylglycerol arrangement does not have a cardiovascular risk and evidences from available in vitro and in vivo studies are not sufficient enough to conclude palm oil as a causative agent for cardiovascular disease. For healthy diet consumers should avoid trans fatty acids, solid and semi solid oils. Finally, further studies recommended on mitigation strategies to minimize process induced toxicants of palm oil to acceptable level.

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.

Trans Fatty Acid (TFA) intake is a risk factor for coronary heart diseases and cancer. Egypt, considered among the highest TFA consumers in the world, lacks proper dietary analysis of TFAs. This cross-sectional study aimed to analyze TFAs in traditional and frequently consumed food products. A market survey was conducted to identify products and brands that are mostly consumed in major governorates in Egypt. Laboratory analysis allowed for the profiling of TFAs, and saturated and unsaturated fatty acids. Products having more than 2 g of TFA/100 g of fat were considered to have an elevated TFA content. Commonly consumed food items (n = 208) in the Egyptian market were identified. On average, 34% of the products exceeded the TFA limit. Sambosk meat, a traditional meat item, had the highest TFA content of 5.2%, followed by foods fried with used oils. Oriental sweets had a TFA content three times higher than that of doughnuts. The fast-food group had the largest proportion of TFA-rich products, followed by the canned and frozen item groups and confectionaries. This study revealed that around one third of products in the Egyptian market have a high TFA content. This calls for urgent legislative action to regulate composition.

Paternal trans-fatty acid and vitamin E diet affects rat offspring's semen quality and PPARs expression.

Trans-fatty acids (TFAs) consumption has created concerns regarding male/female reproductive system. However, the effects of TFA in paternal diet on offspring's reproduction have not been addressed. The purpose of this study is to investigate the effects of rat paternal TFAs and vitamin E consumption on offspring's sperm quality and expression pattern of peroxisome proliferator-activated receptors (PPARs) in testis tissues. Forty adult male rats were randomly divided into four groups: Control diet (C); Control diet plus TFA (CTH); diet supplemented with vitamin E (E) and a diet containing vitamin E and TFA (ETH). Mother rats had normal diet during gestation period. Three offspring from each group were chosen randomly and their testicular samples were collected, and sperm parameters were measured by CASA. Our results indicate that feeding fathers with TFA can negatively affect offspring's sperm concentration and motility, while consumption of vitamin E can improve these parameters (p < .05). The paternal diet containing TFA down-regulated the expression of PPARß and PPARγ genes, whereas vitamin E-containing diet up-regulated the transcription of PPAR genes. In conclusion, TFA intake in paternal diet may have negative effects on reproductive system of the offspring while vitamin E may not diminish these effects.

Industrially produced trans fat: Usage, health implications, global and indian regulations.

Global momentum is growing for the total elimination of industrially produced trans fats from the food systems as they are known to have deleterious health effects on various body functions particularly the cardiovascular health. Many developed nations such as Denmark have completely eliminated the use of industrially produced trans fats from the food supply. India is undergoing a significant nutrition transition that has substantially increased the intake of processed and ready-to-eat foods, abundant in trans fats. The Indian regulator-Food Safety and Standards Authority of India is all set to reduce the industrially produced trans fats to <2% by the end of year 2021 in a phased manner. Multiple strategies such as reducing trans fat limit in oils and fats, mandatory labeling on food products, introduction of "Trans-fat free" claim and logo have been adopted by the Indian regulatory body, to achieve the goal of trans fat free India. This review comprehensively summarizes from a public health perspective the usage of industrially-produced trans fats in Indian food industry, its effects on health, the global strategies to limit its content, and the current Indian regulations.

Interesterified fat consumption since gestation decreases striatal dopaminergic targets levels and gdnf impairing locomotion of adult offspring.

Interesterified fat (IF) currently substitutes the hydrogenated vegetable fat (HVF) in processed foods. However, the IF consumption impact on the central nervous system (CNS) has been poorly studied. The current study investigated connections between IF chronic consumption and locomotor impairments in early life period and adulthood of rats and access brain molecular targets related to behavior changes in adulthood offspring. During pregnancy and lactation, female rats received soybean oil (SO) or IF and their male pups received the same maternal supplementation from weaning until adulthood. Pups' motor ability and locomotor activity in adulthood were evaluated. In the adult offspring striatum, dopaminergic targets, glial cell line-derived neurotrophic factor (GDFN) and lipid profile were quantified. Pups from IF supplementation group presented impaired learning concerning complex motor skill and sensorimotor behavior. The same animals showed decreased locomotion in adulthood. Moreover, IF group showed decreased immunoreactivity of all dopaminergic targets evaluated and GDNF, along with important changes in FA composition in striatum. This study shows that the brain modifications induce by IF consumption resulted in impaired motor control in pups and decreased locomotion in adult animals. Other studies about health damages induced by IF consumption may have a contribution from our current outcomes.

Trans-Fatty Acid (TFA) elimination in Pakistan: A situational analysis.

Recent research studies have highlighted that the consumption of industrially produced trans-fatty acids (TFAs) causes detrimental effects on human health. The World Health Organization (WHO) has recommended the elimination of TFA from diets to reduce the risk of non-communicable diseases (NCDs). In this paper, we use WHO's REPLACE framework for a situation analysis of TFAs in Pakistan's context by reviewing the literature on its dietary and industrial sources along with the legislative and regulatory context surrounding TFA related affairs in Pakistan. To maintain the authenticity of the data and the various actions implemented in Pakistan, we interviewed government officials, experts and researchers engaged in this field. By combining this information with a review of effective policies and best practices applied for TFA elimination around the world, we have prepared recommendations for policymakers in the country. The primary dietary sources of TFA in Pakistan are vanaspati ghee (partially hydrogenated vegetable oil), kinds of margarine, bakery shortenings and fat spreads. Whereas, their main producers are the edible oil, margarine, bakery and confectionary industries. Federal and provincial governments have introduced TFA regulations, but these vary across jurisdictions, complicating enforcement. Lack of credible penalties for violation of regulations, low public awareness and capacity and data gaps among regulators also inhibit TFA elimination. We recommend multi-stakeholder efforts for harmonization of mandatory TFA limits and labeling, replacement of traditional vanaspati ghee, communication efforts for behavioral change, promotion of replacement oils and strengthening regulators' assessment capacities.

Presence of trans fatty acids containing ingredients in pre-packaged foods in Australia in 2018.

OBJECTIVE: The World Health Organization (WHO) has set a goal of prompt, complete and sustained elimination of industrially produced trans fats (iTFA) in the global food supply by 2023. We aimed to assess the number of products in the Australian packaged food supply likely to contain iTFA. METHODS: Using a large pre-packaged food monitoring database collected in 2018, we searched the ingredient list using specific and non-specific ingredient terms to identify products likely to contain iTFA. RESULTS: In total, 28,349 foods were included for analysis: 131 (0.5%) products contained specific ingredients indicative of iTFA, and 1,626 (5.7%) products contained non-specific ingredients that may indicate the presence of iTFA. Bread and bakery products, cereal and grain products and confectionery were the top three food groups that contained specific ingredients indicative of iTFA. Only 19 (14.5%) products with specific iTFA-indicating ingredients declared the amount of trans fats. Conclusions and implications for public health: Compared to other countries, the use of iTFA-containing ingredients is low in Australia, but repeated exposure to products containing iTFA could still put consumers at risk of excessive consumption. Legislation to eliminate iTFA should be considered to minimise the exposure to these harmful chemicals.

Evolution of Trans-fatty acid consumption in Thailand and strategies for its reduction.

Eliminating industrially produced trans-fatty acids (TFAs) from the food supply is one of the World Health Organization's (WHO's) priority targets to control and prevent non-communicable diseases. This review paper describes the strategies used to reduce TFA consumption in Thailand based on a situation analysis consisting of an assessment of TFA content in the national food supply, its intake, and stakeholder-based analysis of Strengths, Weaknesses, Opportunities, and Threats (SWOT). The analysis resulted in the drafting of a regulatory approach, which was then considered by stakeholders. Bakery products containing partially hydrogenated oils (PHOs) are the major sources of TFAs in Thailand. Palm and coconut oil as well as blending technology are locally available as PHO replacements. Thailand's Food and Drug Administration has taken legal action to prohibit the production, import, and distribution of PHOs and their products. Post-marketing TFA levels are currently being monitored, ie, TFAs in fat/oil and butter must not exceed 2% and 6% of fat content, respectively. For other food categories, TFAs must not exceed 0.5 g per serving unless the TFAs are from ruminant sources. The key factor to successfully reducing TFAs in Thailand is the partnership between public and private sectors, professional associations, and consumers, based on scientific evidence regarding the negative impact of TFA intake on cardiovascular health.

Dietary fat intake, erythrocyte fatty acids, and risk of uterine fibroids.

OBJECTIVE: To prospectively evaluate the association between dietary fat intake and risk of uterine fibroids; and to evaluate the association between erythrocyte membrane fatty acid (FA) levels and fibroid risk. DESIGN: Prospective cohort study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence interval (CI). In a subset of participants 34 individual FAs were measured and logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI for the association between FA tertiles and fibroids. SETTING: Not applicable. PATIENT(S): Premenopausal US women (81,590) in the Nurses' Health Study II, aged 25-42 years at enrollment in 1989 for whom diet was assessed by a food frequency questionnaire. A total of 553 participants with erythrocyte FA measurements. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cases of fibroids were defined on the basis of self-reported ultrasound or hysterectomy confirmation. RESULT(S): A total of 8,142 cases of ultrasound-confirmed or hysterectomy-confirmed were diagnosed during an 18-year period (1991-2009). No associations were observed between intake of any dietary fats and fibroids in the multivariable models. However, when erythrocyte FAs were examined, an inverse association was observed between total n-3 polyunsaturated FAs and likelihood of fibroids (OR for third versus first tertile, 0.41; 95% CI 0.19-0.89). In addition, total trans FAs were associated with more odds of fibroids (OR for third tertile, 3.33; 95% CI 1.50-7.38). CONCLUSION(S): Our findings provide preliminary suggestions that n-3 polyunsaturated FAs and trans FAs may play a role in fibroid etiology; however, these results should be confirmed in future studies.

Fatty acids, epigenetic mechanisms and chronic diseases: a systematic review.

BACKGROUND: Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations. METHODS: A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines. RESULTS: Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes. CONCLUSIONS: Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.

Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source.

BACKGROUND: The trans-fat containing AMLN (amylin liver non-alcoholic steatohepatitis, NASH) diet has been extensively validated in C57BL/6J mice with or without the Lepob/Lepob (ob/ob) mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH. Due to a recent ban on trans-fats as food additive, there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice. AIM: To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat. METHODS: Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat (Primex shortening) substituted by equivalent amounts of palm oil [Gubra amylin NASH, (GAN) diet] for 8, 12 and 16 wk. C57BL/6J mice were fed the same diets for 28 wk. AMLN and GAN diets had similar caloric content (40% fat kcal), fructose (22%) and cholesterol (2%) level. RESULTS: The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance. Biopsy-confirmed steatosis, lobular inflammation, hepatocyte ballooning, fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet. C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets. CONCLUSION: Substitution of Primex with palm oil promotes a similar phenotype of biopsy-confirmed NASH in ob/ob and C57BL/6J mice, making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.

Dietary total fat, fatty acids intake, and risk of cardiovascular disease: a dose-response meta-analysis of cohort studies.

BACKGROUND: Several epidemiological studies have investigated the association between dietary fat intake and cardiovascular disease. However, dietary recommendations based on systematic review and meta-analysis might be more credible. METHODS AND RESULTS: Pubmed, Embase and Cochrane library were searched up to July 1st 2018 for cohort studies reporting associations of dietary fat intake and risk of CVDs. By comparing the highest vs. the lowest categories of fat or fatty acids intake, we found that higher dietary trans fatty acids (TFA) intake was associated with increased risk of CVDs [RR:1.14(1.08-1.21)]. However, no association was observed between total fat, monounsaturated fatty acids (MUFA), saturated fatty acids (SFA), and polyunsaturated fatty acids (PUFA), and risk of CVDs. Subgroup analysis found a cardio-protective effect of PUFA in the studies that has been followed up more than 10 years [0.95(0.91-0.99), I2 = 62.4%]. Dose-response analysis suggested that the risk of CVDs increased 16% [1.16 (1.07-1.25), Plinearity = 0.033] for an increment of 2% energy/day of TFA intake. CONCLUSIONS: This current meta-analysis of cohort studies suggested that total fat, SFA, MUFA, and PUFA intake were not associated with the risk of cardiovascular disease. However, we found that higher TFA intake is associated with greater risk of CVDs in a dose-response fashion. Furthermore, the subgroup analysis found a cardio-protective effect of PUFA in studies followed up for more than 10 years.

Dietary Fats in Relation to Total and Cause-Specific Mortality in a Prospective Cohort of 521 120 Individuals With 16 Years of Follow-Up.

RATIONALE: Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. OBJECTIVE: To assess dietary fat intake in relation to total and cause-specific mortality. METHODS AND RESULTS: We analyzed data of 521 120 participants aged 50 to 71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study with 16 years of follow-up. Intakes of saturated fatty acids (SFAs), trans-fatty acids, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were assessed via food frequency questionnaires. Hazard ratios and 95%CIs were estimated using the Cox proportional hazards model. Overall, 129 328 deaths were documented during 7.3 million person-years of follow-up. In the replacement of carbohydrates, multivariable-adjusted hazard ratios of total mortality comparing extreme quintiles were 1.29 (95% CI, 1.25-1.33) for SFAs, 1.03 (1.00-1.05) for trans-fatty acids, 0.98 (0.94-1.02) for MUFAs, 1.09 (1.06-1.13) for animal MUFAs, 0.94 (0.91-0.97) for plant MUFAs, 0.93 (0.91-0.95) for PUFAs, 0.92 (0.90-0.94) for marine omega-3 PUFAs, 1.06 (1.03-1.09) for α-linolenic acid, 0.88 (0.86-0.91) for linoleic acid, and 1.10 (1.08-1.13) for arachidonic acid. CVD mortality was inversely associated with marine omega-3 PUFA intake ( P trend <0.0001), whereas it was positively associated with SFA, trans-fatty acid, and arachidonic acid intake. Isocalorically replacing 5% of the energy from SFAs with plant MUFAs was associated with 15%, 10%, 11%, and 30% lower total mortality, CVD, cancer, and respiratory disease mortality, respectively. Isocaloric replacement of SFA with linoleic acid (2%) was associated with lower total (8%), CVD (6%), cancer (8%), respiratory disease (11%), and diabetes mellitus (9%) mortality. CONCLUSIONS: Intakes of SFAs, trans-fatty acids, animal MUFAs, α-linolenic acid, and arachidonic acid were associated with higher mortality. Dietary intake of marine omega-3 PUFAs and replacing SFAs with plant MUFAs or linoleic acid were associated with lower total, CVD, and certain cause-specific mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.