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Molecular Immune-Inflammatory Connections between Dietary Fats and Atherosclerotic Cardiovascular Disease: Which Translation into Clinics?
Mattavelli, E, Catapano, AL, Baragetti, A
Nutrients. 2021;(11)
Abstract
Current guidelines recommend reducing the daily intake of dietary fats for the prevention of ischemic cardiovascular diseases (CVDs). Avoiding saturated fats while increasing the intake of mono- or polyunsaturated fatty acids has been for long time the cornerstone of dietary approaches in cardiovascular prevention, mainly due to the metabolic effects of these molecules. However, recently, this approach has been critically revised. The experimental evidence, in fact, supports the concept that the pro- or anti-inflammatory potential of different dietary fats contributes to atherogenic or anti-atherogenic cellular and molecular processes beyond (or in addition to) their metabolic effects. All these aspects are hardly translatable into clinics when trying to find connections between the pro-/anti-inflammatory potential of dietary lipids and their effects on CVD outcomes. Interventional trials, although providing stronger potential for causal inference, are typically small sample-sized, and they have short follow-up, noncompliance, and high attrition rates. Besides, observational studies are confounded by a number of variables and the quantification of dietary intakes is far from optimal. A better understanding of the anatomic and physiological barriers for the absorption and the players involved in the metabolism of dietary lipids (e.g., gut microbiota) might be an alternative strategy in the attempt to provide a first step towards a personalized dietary approach in CVD prevention.
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Dietary carbohydrates and fats in nonalcoholic fatty liver disease.
Yki-Järvinen, H, Luukkonen, PK, Hodson, L, Moore, JB
Nature reviews. Gastroenterology & hepatology. 2021;(11):770-786
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Abstract
The global prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased in parallel with the epidemic of obesity. Controversy has emerged around dietary guidelines recommending low-fat-high-carbohydrate diets and the roles of dietary macronutrients in the pathogenesis of metabolic disease. In this Review, the topical questions of whether and how dietary fats and carbohydrates, including free sugars, differentially influence the accumulation of liver fat (specifically, intrahepatic triglyceride (IHTG) content) are addressed. Focusing on evidence from humans, we examine data from stable isotope studies elucidating how macronutrients regulate IHTG synthesis and disposal, alter pools of bioactive lipids and influence insulin sensitivity. In addition, we review cross-sectional studies on dietary habits of patients with NAFLD and randomized controlled trials on the effects of altering dietary macronutrients on IHTG. Perhaps surprisingly, evidence to date shows no differential effects between free sugars, with both glucose and fructose increasing IHTG in the context of excess energy. Moreover, saturated fat raises IHTG more than polyunsaturated or monounsaturated fats, with adverse effects on insulin sensitivity, which are probably mediated in part by increased ceramide synthesis. Taken together, the data support the use of diets that have a reduced content of free sugars, refined carbohydrates and saturated fat in the treatment of NAFLD.
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Dietary Saturated Fats and Health: Are the U.S. Guidelines Evidence-Based?
Astrup, A, Teicholz, N, Magkos, F, Bier, DM, Brenna, JT, King, JC, Mente, A, Ordovas, JM, Volek, JS, Yusuf, S, et al
Nutrients. 2021;(10)
Abstract
The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats and cardiovascular outcomes, which, altogether, have demonstrated a lack of rigorous evidence to support continued recommendations either to limit the consumption of saturated fatty acids or to replace them with polyunsaturated fatty acids. These papers were unfortunately not considered by the process leading to the most recent U.S. Dietary Guidelines for Americans, the country's national nutrition policy, which recently reconfirmed its recommendation to limit saturated fats to 10% or less of total energy intake, based on insufficient and inconsistent evidence. Continuation of a cap on saturated fat intake also fails to consider the important effects of the food matrix and the overall dietary pattern in which saturated fatty acids are consumed.
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Dietary Fat Effect on the Gut Microbiome, and Its Role in the Modulation of Gastrointestinal Disorders in Children with Autism Spectrum Disorder.
Kittana, M, Ahmadani, A, Al Marzooq, F, Attlee, A
Nutrients. 2021;(11)
Abstract
Children with autism spectrum disorder (ASD) report a higher frequency and severity of gastrointestinal disorders (GID) than typically developing (TD) children. GID-associated discomfort increases feelings of anxiety and frustration, contributing to the severity of ASD. Emerging evidence supports the biological intersection of neurodevelopment and microbiome, indicating the integral contribution of GM in the development and function of the nervous system, and mental health, and disease balance. Dysbiotic GM could be a contributing factor in the pathogenesis of GID in children with ASD. High-fat diets may modulate GM through accelerated growth of bile-tolerant bacteria, altered bacterial ratios, and reduced bacterial diversity, which may increase the risk of GID. Notably, saturated fatty acids are considered to have a pronounced effect on the increase of bile-tolerant bacteria and reduction in microbial diversity. Additionally, omega-3 exerts a favorable impact on GM and gut health due to its anti-inflammatory properties. Despite inconsistencies in the data elaborated in the review, the dietary fat composition, as part of an overall dietary intervention, plays a role in modulating GID, specifically in ASD, due to the altered microbiome profile. This review emphasizes the need to conduct future experimental studies investigating the effect of diets with varying fatty acid compositions on GID-specific microbiome profiles in children with ASD.
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trans-Fatty Acids as an Enhancer of Inflammation and Cell Death: Molecular Basis for Their Pathological Actions.
Hirata, Y
Biological & pharmaceutical bulletin. 2021;(10):1349-1356
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Abstract
trans-Fatty acids (TFAs) are food-derived fatty acids that possess one or more trans double bonds between carbon atoms. Compelling epidemiological and clinical evidence has demonstrated the association of TFA consumption with various diseases, such as cardiovascular diseases, and neurodegenerative diseases. However, the underlying etiology is poorly understood since the mechanisms of action of TFAs remain to be clarified. Previous studies have shown that single treatment with TFAs induce inflammation and cell death, but to a much lesser extent than saturated fatty acids (SFAs) that are well established as a risk factor for diseases linked with inflammation and cell death, which cannot explain the particularly higher association of TFAs with atherosclerosis than SFAs. In our series of studies, we have established the role of TFAs as an enhancer of inflammation and cell death. We found that pretreatment with TFAs strongly promoted apoptosis induced by either extracellular ATP, one of the damage-associated molecular patterns (DAMPs) leaked from damaged cells, or DNA damaging-agents, including doxorubicin and cisplatin, thorough enhancing activation of the stress-responsive mitogen-activated protein (MAP) kinase p38/c-jun N-terminal kinase (JNK) pathways; pretreatment with SFAs or cis isomers of TFAs had only minor or no effect, suggesting the uniqueness of the pro-apoptotic role of TFAs among fatty acids. Our findings will provide an insight into understanding of the pathogenesis mechanisms, and open up a new avenue for developing prevention strategies and therapies for TFA-related diseases.
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Total Dietary Fat Intake, Fat Quality, and Health Outcomes: A Scoping Review of Systematic Reviews of Prospective Studies.
Schwingshackl, L, Zähringer, J, Beyerbach, J, Werner, SS, Heseker, H, Koletzko, B, Meerpohl, JJ
Annals of nutrition & metabolism. 2021;(1):4-15
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Abstract
INTRODUCTION We conducted a scoping review of systematic reviews (SRs) on dietary fat intake and health outcomes in human adults within the context of a position paper by the "International Union of Nutritional Sciences Task force on Dietary Fat Quality" tasked to summarize the available evidence and provide dietary recommendations. METHODS We systematically searched several databases for relevant SRs of randomized controlled trials (RCTs) and/or prospective cohort studies published between 2015 and 2019 assessing the association between dietary fat and health outcomes. RESULTS Fifty-nine SRs were included. The findings from SRs of prospective cohort studies, which frequently compare the highest versus lowest intake categories, found mainly no association of total fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) with risk of chronic diseases. SRs of RCTs applying substitution analyses indicate that SFA replacement with PUFA and/or MUFA improves blood lipids and glycemic control, with the effect of PUFA being more pronounced. A higher intake of total trans-fatty acid (TFA), but not ruminant TFA, was probably associated with an increased risk of mortality and cardiovascular disease based on existing SRs. CONCLUSION Overall, the available published evidence deems it reasonable to recommend replacement of SFA with MUFA and PUFA and avoidance of consumption of industrial TFA.
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Involvement of the Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease.
Zhou, X, Fouda, S, Li, D, Zhang, K, Ye, JM
Nutrients. 2020;(9)
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease that can progress from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), and even further to liver cirrhosis or liver cancer. Overconsumption of high fat and/or carbohydrate are among the most common lifestyle factors that drive the development and progression of NAFLD. This review evaluates recent reports on the involvement of autophagy and endoplasmic reticulum (ER) stress in the pathogenesis of NAFLD. Here, we reveal a mechanism of an intrinsically linked axis of impaired autophagy and unresolved ER stress that mediates the development and progression of NAFLD resulting from the overconsumption of high fat and/or carbohydrate.
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Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review.
Astrup, A, Magkos, F, Bier, DM, Brenna, JT, de Oliveira Otto, MC, Hill, JO, King, JC, Mente, A, Ordovas, JM, Volek, JS, et al
Journal of the American College of Cardiology. 2020;(7):844-857
Abstract
The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods.
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Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury.
Ramiro-Cortijo, D, Singh, P, Liu, Y, Medina-Morales, E, Yakah, W, Freedman, SD, Martin, CR
Nutrients. 2020;(2)
Abstract
Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.
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Diet Quality, Saturated Fat and Metabolic Syndrome.
Harrison, S, Couture, P, Lamarche, B
Nutrients. 2020;(11)
Abstract
Indices reflecting overall diet quality are used globally in research to predict the risk of various diseases and metabolic disorders such as metabolic syndrome (MetS). Such indices are built to measure adherence to current dietary guidelines or to best assess the diet-disease relationship. Although mostly food-based, dietary guidelines often include recommendations to limit saturated fatty acid (SFA) intake in order to prevent cardiovascular diseases. However, not all diet quality indices consider SFA in their definition of diet quality. Additionally, the relationship between SFA consumption and the development of MetS remains unclear. The purpose of this short review was to explore the association between MetS and various diet quality indices and dietary patterns, with a focus on how SFA contributes to these associations.