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fats
Eicosanoid Metabolism
Nutrition
Definition
Eicosanoid Metabolism
Eicosanoids are 20 carbon chain fatty acids composed from essential fatty acids. Eicosanoid metabolism is complex and there are many things we do not know. From theoretical and clinical perspectives, we have learned a great deal about various pathways and some of the clinical effects of ingesting these oils. There are many ways to classify fats. One way is to classify them according to the series of prostaglandins to which they give rise. Below is the general scheme.
Linoleic acid 18:2n-6 (omega 6 fatty acid)This oil is found in many nuts and seeds including safflower, sunflower, sesame, soy bean, corn, cottonseed, and wheat germ (in approximate descending order). These oils eventually get converted into series 1 prostaglandins (PGE1). PGE1 relaxes smooth muscles; decreases platelet aggregation; prevents the release of arachidonic acid from cell membranes, thus decreasing the amount of inflammatory substrate available; enhances mucin production in the stomach for protection; inhibits tumor growth; decreases inflammation; stabilizes red blood cell membranes; and blocks the conversion of arachidonic acid into inflammatory eicosanoids.
NOTE: Because there has been a lot of misinformation concerning the conversion of one of linoleic acids metabolites dihomogamma linolenic acid an important point needs to made. In most biochemistry text books, and in many less technical books and periodicals on the subject, it is stated that DHGLA gets converted to arachidonic acid via the enzyme delta 5 desaturase. This may be true in certain mammalian species such as rats and mice, but in humans this conversion is very slow. The activity of the enzyme delta 5 desaturase is minimal in humans, rabbits and guinea pigs. In addition, both DHGLA and GLA actually inhibit the action of delta 5 desaturase. It is sometimes mentioned that GLA supplements can be harmful because they increase the levels of arachidonic acid in the body which also increases inflammation. This is not true in humans. Only small amounts of arachidonic acid are produced and this small amount is blocked in its transformation into inflammatory mediators by delta 5 desaturase.
PGE1 Derived from omega 6 fatty acidswhich are found in many nuts, seeds and grains as well as evening primrose, borage and blackcurrent oilsPGE1 has many effects. These include keeping blood pressure under control, regulating the secretion of the protective substances of the stomach, reducing inflammation and influencing mood and emotions. There are certain pathologiessuch as diabetes, alcoholism, hypertension, and atopic dermatitisthat involve a decreased production of PGE1. The enzyme delta 6 desaturase is the rate limiting enzyme for the production of PGE1. A synthetic analog of PGE1, "Cytotek," is sometimes prescribed for the prevention of stomach ulcers when NSAIDS are being used to treat inflammation. Certain nationalities such as Irish, Celtic, Scandanavian, Scottish and Native American have deficiencies of delta 6 desaturase and may require the more immediate precursor (GLA) to generate adequate levels of PGE1. It should also be noted that DHGLA may have more properties of its own as it generates some unique metabolites that have not been studied much yet.
PGE2 Derived from arachidonic acid, 20-4 omega 6, which comes almost entirely from animal derived foods, PGE2 is responsible for generating the bodys inflammatory response. This is vital for normal immune function. It acts to increase platelett aggregation, increase permeability, increase temperature, pain, and increase contraction of smooth muscle in the blood vessels. However, in many disease processes the reduction in these prostaglandins is very important in improving the condition. Most inflammatory conditions, as well as asthma and cardiovascular pathologies, benefit from a reduction of PGE2. Aspirin has been found to decrease production of PGE2. It is believed that this is the mechanism by which it exerts its anti-inflammatory effects is by blocking the cycbooxygenase, the enzyme that is critical for converting arachidonic acid into PGE2.
PGE3 Derived from omega 3 fatty acids, this prostaglandin is responsible for anti-inflammatory action, decreasing platelet adhesiveness, decreasing serum triglycerides and improving the integrity of cell membranes. It has also been shown to have a regulatory effect on blood pressure similar to PGE 1. Generally, it is in a balance with the other prostaglandins, especially PGE 1. Currently, PGE3 levels in the U.S. are probably on the deficient side because the U.S. diet is very low in omega 3 fatty acids. Like PGE 1, the rate limiting enzyme for PGE3 production is delta 6 desaturase which can be antagonized by a number of different factors such as coffee, insulin, trans fatty acids, alcohol, and aging. It is believed that our diet as hunters and gatherers was much higher in omega 3 fatty acids, therefore our levels of PGE3 were considerably higher.
In some people there may be a problem converting alpha linolenic acid into Eicosahexaenoic acid, 20:5 omega 3 (EPA) and docosahexaenoic acid, 22:6 omega 3(DHA). In such cases, it may be necessary to directly supply these in the diet either through foods or supplements. In infancy DHA is supplied directly through mothers milk. Infants not receiving this DHA (formula fed infants) have been found to develop their brain function and visual acuity more slowly.
(Marz R, 47-48)
Footnotes
Flax Oil and Prostaglandin Synthesis. Nutrition 8:211-212, 1992.
Abstract: Alpha linolenic acid was shown to decrease the levels of arachonicdonic acid. This suppression of arachidonic acid was found to be dependant upon the dose of alpha linolenic acid unless linoleic acid intake was allowed to go up.
GLA in diabetes: Resultsfrom the GM Multicenter Trial Gruppi. Diabetes Care. 16:8-15, 1993.
Abstract: In 111 pts with mild diabetic neuropathy, it was shown that GLA 480mg/day over the course of 1 year prevented further deterioration and in some cases was seen to actually get better.
GM in RA:Results form a double blind study. AnnaJs of Internal Medicine. 119:867-873, 1993.
Abstract: 1 .4gms/day of GLA was given in form of borage oil while they were taking their NSAIDS. There was a significantly reduced number and vereity of painful joints in 37 patients after 24 weeks.
Marz, Russell. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.
Omega 3 oils in RA:Results form a long term double blind study. Arthritis and Rheumatism 37:824-9, 1994.
Abstract: 90 patients with RA were treated with 2.Sgms omega 3 oils from fish for 12 months. There was a significant clinical benefit from both subjective and objective evaluations.
Willis, AL. Handbook of the Eicosanoids: Prostaglandins and Related Lipids. Boca Raton, FL: CRC Press, Inc., August 1989. A.L. Willis is probably the formost expert in the field of Eicosanoid metabolism, Prostaglandins and Fats. Much of the cuurent research that has been done he has been involved with.