Omega-3 Fatty Acids and Inflammatory Processes
Prostaglandins Leukot Essent Fatty Acids. May;46(1) The relationship between schizophrenia and essential fatty acid and eicosanoid metabolism. There are four families of eicosanoids—the prostaglandins, prostacyclins, the They are derived from oxidation of essential fatty acids, generally Omega-3 or. Thus, the synthesis of pro-inflammatory eicosanoids is suppressed in the Dietary and Supplemented Essential Fatty Acids and Eicosanoid Synthesis. Of . Association of frequency and duration of aspirin use and hormone.
The North American diet, with its high animal-fat content and generous use of oils rich in LA, provides cells with generous amounts of polyunsaturated fats AA from which to produce prostanoids and leukotrienes that promote inflammation, cardiovascular disease and cancer.
In turn, this blocks the conversion of LA into AA. Thus, flaxseed oil supplementation not only provides raw materials from which the body can make EPA, as well as DHA, which is important for vision and brain function throughout life ; ALA also helps to decrease membrane concentrations of AA by blocking the conversion of LA into AA. LA is oversupplied by the North American and Western diet.
Thus, this lack of conversion helps the synthesis of health-promoting eicosanoids and the suppression of inflammation-promoting eicosanoids. In regard to promotion of inflammation, prostaglandin E2 PGE-2formed from activation of AA by cyclooxygenase, acts inside the cell to produce various types and quantities of cytokines, which are pro-inflammatory agents that bring active leukocytes to the injury site.
Many leukocytes white blood cells convert AA into pro-inflammatory leukotrienes via 5-lipoxygenase enzyme, such as pro-inflammatory leukotriene B4 LTB4which makes local blood vessels more permeable.
In turn, plasma leaks out into the connective tissues, causing more swelling. PGE2 also sensitizes pain-nerve endings, increasing pain from the inflamed tissues.
However, conversion slows down as we age, allowing inflammatory states to occur more easily. In this regard, many health experts recommend daily supplementation withmg of borage seed oil which is 22 percent GLA, compared to only 9 percent GLA in evening primrose oil. EPA acts as a precursor for pro-staglandin-3 and promotes the synthesis of leukotriene-5 groups, all of which suppress the inflammatory response.
In regard to cardiovascular disease, a prostanoid synthesized from AA via cyclooxygenase namely thromboxane A2 increases risk of cardiovascular disease by constricting blood vessels, increasing smooth muscle tone and by increasing platelet coagulation. Platelet coagulation, forming a plug in the artery wall in the area of atherosclerosis developmentis often the final precipitating event leading to a myocardial infarction, angina or other ischemic vascular event.
Thromboxane A2 is synthesized with platelets. Interestingly, endothelial cells in the blood vessel wall synthesize an anti-platelet aggregatory protanoid from AA, known as prostacyclin I-2 PGI2.
However, high tissue concentrations of AA tend to produce a strong vasoconstriction response and enhance platelet aggregation due to the synthesis of thromboxane A2. This generally supersedes the anti-aggregatory influence of endothelial-derived PGI2. However, higher tissue levels of EPA permits the anti-aggregation effects of PGI2 to be expressed with greater influence, helping to reduce the risk of many ischemic cardiovascular events.
Reduction of the pro-aggregatory, vasoconstrictive TXA2 decreases the thrombotic tendency of platelets, reducing risk of cardiovascular disease. This is augmented by the limited depression of the vasoactive anti-aggregatory prostacyclin PGI2 secreted by endothelial cells and the generation of anti-aggregatory prostaglandin I-3 PGI3 from EPA. EPA has been shown to reduce blood pressure and blood viscosity and modulate membrane fluidity and associated enzyme and receptor functions.
Essential Fatty Acids and Eicosanoids
The collective effects of omega-3 fatty acids likely account for the reduction in coronary arterial disease in populations consuming foods rich in omega-3 fatty acids. Abundant evidence suggests that the conversion of AA into various leukotrienes via the 5-lipoxygenase enzyme and the lipoxygenase enzymes has a profound influence on the development and progression of human cancers.
Compared with normal tissues, significantly elevated metabolites of the lipoxygenase pathway using AA as the essential fatty acidare common features in lung, prostate, breast, colon and skin cancers, as well as in cells from patients with both acute and chronic leukemia. Lipoxygenase end-products derived from AA especially leukotriene A4 and 5-hydroxyeicosatetraenoic acid elicit diverse biological activities required for neoplastic cell growth.
They influence cellular growth factors, transcription factor activation which up-regulates oncogenes and oncogene induction. They also help to inhibit programmed cell death apoptosis and influence other factors important for cancer cell survival, progression and metastasis. As well, prostanoids derived from AA have been shown to stimulate cell proliferation, which increases risk for cancer development and promotes proliferation of existing possibly latent cancer cells.
In turn, this inhibits the synthesis of PGE2 and other prostanoids formed from AA, which are involved in inflammation, platelet aggregation, vasoconstriction and cellular proliferation. In this regard, NSAIDs have been used to reduce inflammation, pain and fever, as well as to reduce platelet stickiness in an effort to reduce risk of coronary disease.
Experimental and epidemiological studies recognize that these drugs also may offer protection against certain cancers by slowing cellular proliferation.
In fact, 10, to 20, individuals die each year in the United States from bleeding disorders and other complications induced by the frequent use of NSAIDs. As such, their application as prophylactic agents in cancer prevention may place individuals at risk for other life-threatening health conditions. Experimental, preclinical and preliminary studies indicate that these natural compounds are able to suppress cancer development and block the recurrence of cancer in colon cancer patients. Highly effective agents include curcumin, white willow extract, ginger, boswellia and quercetin.
Each of these natural compounds has been used to effectively treat a variety of joint inflammatory conditions and also may hold promise as natural interventions to help prevent cancer by blocking the conversion of AA to prostanoid metabolites cyclooxygenase inhibition.
EPA also has been shown to compete with AA for activation via the lipoxygenase enzyme system, helping to reduce AA-derived metabolites that spur the growth and spread of cancer. This article has drawn attention to the impact that polyunsaturated fatty acid consumption has on the eicosanoid cascade, and the effect that various eicosanoids have on these prevalent health conditions.
Based on the available evidence, I recommend that health practitioners encourage their patients to do the following: For general prevention and wellness, individuals should consider two or three capsules per day.
Individuals with certain health problems may require higher, more therapeutic doses. Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: Am J Clin Nutr, ; Pharmacology for the Primary Care Provider, 2nd ed.
Importance of dietary gamma -linolenic acid in human health and nutrition. J Nutr, ; 9: The effect of eicosapentaenoic acid on leukotriene B production by human neutrophils. J Biol Chem, ; Sacks FM, Katan M.
Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Am J Med, ; Suppl 9B: Workshop statement on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids.
Prostaglandins Leukot Essent Fatty Acids, ; Fatty acid modulation of endothelial activation.
Structural Biochemistry/Lipids/Fatty Acids/Eicosanoids
Sacks FM, Campos H. Polyunsaturated fatty acids, inflammation, and cardiovascular disease: J Clin Endocrinol Meta;91 2: Lipoxygenase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev, ;8 5: A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence.
This may reflect white blood cells' lack of desaturase. Animal studies indicate the effect is small.
It is therefore difficult to characterize the action of any particular eicosanoid. Each is coded by a separate gene, and some exist in multiple isoforms.
Each EP receptor in turn couples to a G protein. This increases intracellular cAMP and is anti-inflammatory. EP1 and other EP3 isoforms couple to Gq.
This leads to increased intracellular calcium and is pro-inflammatory. Many immune-system cells express multiple receptors that couple these apparently opposing pathways. The arachidonic acid cascade in the central nervous system CNS [ edit ] The arachidonic acid cascade is arguably the most elaborate signaling system neurobiologists have to deal with.
Daniele Piomelli Arachidonic Acid  The arachidonic acid cascade proceeds somewhat differently in the brain. Neurohormonesneuromodulators or neurotransmitters act as first messengers.
They activate phospholipidase to release AA from neuron cell membranes as a free fatty acid. During its short lifespan, free AA may affect the activity of the neuron's ion channels and protein kinases. Or it may be metabolized to form eicosanoids, epoxyeicosatrienoic acids EETsneuroprotectin D or various endocannabinoids anandamide and its analogs.