Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present ...article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance.
Inflammation is a condition which contributes to a range of human diseases. It involves a multitude of cell types, chemical mediators, and interactions. Eicosapentaenoic acid (EPA) and ...docosahexaenoic acid (DHA) are omega-3 (n−3) fatty acids found in oily fish and fish oil supplements. These fatty acids are able to partly inhibit a number of aspects of inflammation including leukocyte chemotaxis, adhesion molecule expression and leukocyte–endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n−6 fatty acid arachidonic acid, production of inflammatory cytokines, and T-helper 1 lymphocyte reactivity. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of marine n−3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor peroxisome proliferator activated receptor γ and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked, although the full extent of this is not yet elucidated. Animal experiments demonstrate benefit from marine n−3 fatty acids in models of rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in RA demonstrate benefit, but clinical trials of fish oil in IBD and asthma are inconsistent with no overall clear evidence of efficacy. This article is part of a Special Issue entitled “Oxygenated metabolism of PUFA: analysis and biological relevance”.
•Inflammation is a condition which contributes to a range of human diseases.•Marine n−3 fatty acids partly inhibit a number of aspects of inflammation.•Several mechanisms explain the anti-inflammatory actions of marine n−3 fatty acids.•Animal experiments demonstrate benefits of marine n−3 fatty acids.•Trials of marine n−3 fish oil in patients are generally inconsistent.
Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant ...signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.
Nutrition, immunity and COVID-19 Calder, Philip C
BMJ nutrition, prevention & health,
06/2020, Volume:
3, Issue:
1
Journal Article
Peer reviewed
Open access
The immune system protects the host from pathogenic organisms (bacteria, viruses, fungi, parasites). To deal with this array of threats, the immune system has evolved to include a myriad of ...specialised cell types, communicating molecules and functional responses. The immune system is always active, carrying out surveillance, but its activity is enhanced if an individual becomes infected. This heightened activity is accompanied by an increased rate of metabolism, requiring energy sources, substrates for biosynthesis and regulatory molecules, which are all ultimately derived from the diet. A number of vitamins (A, B6, B12, folate, C, D and E) and trace elements (zinc, copper, selenium, iron) have been demonstrated to have key roles in supporting the human immune system and reducing risk of infections. Other essential nutrients including other vitamins and trace elements, amino acids and fatty acids are also important. Each of the nutrients named above has roles in supporting antibacterial and antiviral defence, but zinc and selenium seem to be particularly important for the latter. It would seem prudent for individuals to consume sufficient amounts of essential nutrients to support their immune system to help them deal with pathogens should they become infected. The gut microbiota plays a role in educating and regulating the immune system. Gut dysbiosis is a feature of disease including many infectious diseases and has been described in COVID-19. Dietary approaches to achieve a healthy microbiota can also benefit the immune system. Severe infection of the respiratory epithelium can lead to acute respiratory distress syndrome (ARDS), characterised by excessive and damaging host inflammation, termed a cytokine storm. This is seen in cases of severe COVID-19. There is evidence from ARDS in other settings that the cytokine storm can be controlled by n-3 fatty acids, possibly through their metabolism to specialised pro-resolving mediators.
A variety of fatty acids exists in the diet of humans, in the bloodstream of humans, and in cells and tissues of humans. Fatty acids are energy sources and membrane constituents. They have biological ...activities that act to influence cell and tissue metabolism, function, and responsiveness to hormonal and other signals. The biological activities may be grouped as regulation of membrane structure and function; regulation of intracellular signaling pathways, transcription factor activity, and gene expression; and regulation of the production of bioactive lipid mediators. Through these effects, fatty acids influence health, well-being, and disease risk. The effects of saturated, cis monounsaturated, ω-6 and ω-3 polyunsaturated, and trans fatty acids are discussed. Although traditionally most interest in the health impact of fatty acids related to cardiovascular disease, it is now clear that fatty acids influence a range of other diseases, including metabolic diseases such as type 2 diabetes, inflammatory diseases, and cancer. Scientists, regulators, and communicators have described the biological effects and the health impacts of fatty acids according to fatty acid class. However, it is now obvious that within any fatty acid class, different members have different actions and effects. Thus, it would seem more appropriate to describe biological effects and health impacts of individual named fatty acids, although it is recognized that this would be a challenge when communicating outside of an academic environment (eg, to consumers).
The definition of what constitutes a healthy diet is continually shifting to reflect the evolving understanding of the roles that different foods, essential nutrients, and other food components play ...in health and disease. A large and growing body of evidence supports that intake of certain types of nutrients, specific food groups, or overarching dietary patterns positively influences health and promotes the prevention of common non-communicable diseases (NCDs). Greater consumption of health-promoting foods and limited intake of unhealthier options are intrinsic to the eating habits of certain regional diets such as the Mediterranean diet or have been constructed as part of dietary patterns designed to reduce disease risk, such as the Dietary Approaches to Stop Hypertension (DASH) or Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. In comparison with a more traditional Western diet, these healthier alternatives are higher in plant-based foods, including fresh fruits and vegetables, whole grains, legumes, seeds, and nuts and lower in animal-based foods, particularly fatty and processed meats. To better understand the current concept of a "healthy diet," this review describes the features and supporting clinical and epidemiologic data for diets that have been shown to prevent disease and/or positively influence health. In total, evidence from epidemiological studies and clinical trials indicates that these types of dietary patterns reduce risks of NCDs including cardiovascular disease and cancer.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n‐3 fatty acids found in oily fish and fish oil supplements. These fatty acids are able to inhibit partly a number of aspects of ...inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte‐endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n‐6 fatty acid arachidonic acid, production of inflammatory cytokines and T cell reactivity. In parallel, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonioc acid and EPA and DHA give rise to anti‐inflammatory and inflammation resolving resolvins and protectins. Mechanisms underlying the anti‐inflammatory actions of n‐3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro‐inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti‐inflammatory transcription factor NR1C3 (i.e. peroxisome proliferator activated receptor γ) and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked. In adult humans, an EPA plus DHA intake greater than 2 g day–1 seems to be required to elicit anti‐inflammatory actions, but few dose finding studies have been performed. Animal models demonstrate benefit from n‐3 fatty acids in rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in patients with RA demonstrate benefit supported by meta‐analyses of the data. Clinical trails of fish oil in patients with IBD and asthma are inconsistent with no overall clear evidence of efficacy.
Obesity leads to an inflammatory condition that is directly involved in the etiology of cardiovascular diseases, type 2 diabetes mellitus, and certain types of cancer. The classic inflammatory ...response is an acute reaction to infections or to tissue injuries, and it tends to move towards resolution and homeostasis. However, the inflammatory process that was observed in individuals affected by obesity and metabolic syndrome differs from the classical inflammatory response in certain respects. This inflammatory process manifests itself systemically and it is characterized by a chronic low-intensity reaction. The toll-like receptor 4 (TLR4) signaling pathway is acknowledged as one of the main triggers of the obesity-induced inflammatory response. The aim of the present review is to describe the role that is played by the TLR4 signaling pathway in the inflammatory response and its modulation by saturated and omega-3 polyunsaturated fatty acids. Studies indicate that saturated fatty acids can induce inflammation by activating the TLR4 signaling pathway. Conversely, omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exert anti-inflammatory actions through the attenuation of the activation of the TLR4 signaling pathway by either lipopolysaccharides or saturated fatty acids.
Eicosanoids Calder, Philip C
Essays in biochemistry,
09/2020, Volume:
64, Issue:
3
Journal Article
Peer reviewed
Open access
This article describes the pathways of eicosanoid synthesis, eicosanoid receptors, the action of eicosanoids in different physiological systems, the roles of eicosanoids in selected diseases, and the ...major inhibitors of eicosanoid synthesis and action. Eicosanoids are oxidised derivatives of 20-carbon polyunsaturated fatty acids (PUFAs) formed by the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (cytP450) pathways. Arachidonic acid (ARA) is the usual substrate for eicosanoid synthesis. The COX pathways form prostaglandins (PGs) and thromboxanes (TXs), the LOX pathways form leukotrienes (LTs) and lipoxins (LXs), and the cytP450 pathways form various epoxy, hydroxy and dihydroxy derivatives. Eicosanoids are highly bioactive acting on many cell types through cell membrane G-protein coupled receptors, although some eicosanoids are also ligands for nuclear receptors. Because they are rapidly catabolised, eicosanoids mainly act locally to the site of their production. Many eicosanoids have multiple, sometimes pleiotropic, effects on inflammation and immunity. The most widely studied is PGE2. Many eicosanoids have roles in the regulation of the vascular, renal, gastrointestinal and female reproductive systems. Despite their vital role in physiology, eicosanoids are often associated with disease, including inflammatory disease and cancer. Inhibitors have been developed that interfere with the synthesis or action of various eicosanoids and some of these are used in disease treatment, especially for inflammation.
Numerous effects of n-3 fatty acids EPA and DHA on functional responses of cells involved in inflammation and immunity have been described. Fatty acid-induced modifications in membrane order and in ...the availability of substrates for eicosanoid synthesis are long-standing mechanisms that are considered important in explaining the effects observed. More recently, effects on signal transduction pathways and on gene expression profiles have been identified. Over the last 10 years or so, significant advances in understanding the mechanisms of action of n-3 fatty acids have been made. These include the identification of new actions of lipid mediators that were already described and of novel interactions among those mediators and the description of an entirely new family of lipid mediators, resolvins and protectins that have anti-inflammatory actions and are critical to the resolution of inflammation. It is also recognised that EPA and DHA can inhibit activation of the prototypical inflammatory transcription factor NF-κB. Recent studies suggest three alternative mechanisms by which n-3 fatty acids might have this effect. Within T-cells, as well as other cells of relevance to immune and inflammatory responses, EPA and DHA act to disrupt very early events involving formation of the structures termed lipid rafts which bring together various proteins to form an effective signalling platform. In summary, recent research has identified a number of new mechanisms of action that help to explain previously identified effects of n-3 fatty acids on inflammation and immunity.
PDF
