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westonaprice.org has an excellent article on prostaglandins, from which I’ve extracted some parts

Function

{@weston}

Prostaglandins are produced in the cells by the action of enzymes on essential fatty acids. There are two prostaglandin pathways, one that begins with double-unsaturated omega-6 linoleic acid and one that begins with triple-unsaturated omega-3 alpha-linolenic acid. Both pathways essentially involve elongation of the 18-carbon EFA’s to the 20-carbon root used in each of the three eicosanoid types, plus further desaturation.
On the omega-6 pathway, the Series 1 prostaglandins are produced from a 20-carbon, triple unsaturated fatty acid called dihomo-y-linolenic acid (DGLA) that is found in liver and other organ meats. The Series 2 prostaglandins are produced from a 20-carbon quadruple unsaturated fatty acid called arachidonic acid (AA) found in butter, animal fats, especially pork, organ meats, eggs and seaweed. On the omega-3 pathway, the Series 3 prostaglandins are produced from a 20-carbon quintuple unsaturated fatty acid called eicosapentaenoic acid (EPA) found plentifully in fish liver oils and fish eggs.

In the simplest terms, the Series 2 prostaglandins seem to be involved in swelling, inflammation, clotting and dilation, while those of the Series 1 group have the opposite effect. This has led some writers, notably Barry Sears in his popular book The Zone, to call the Series 2 family the “bad” eicosanoids and to warn readers against eating liver and butter, sources of arachidonic acid, the Series 2 precursor. Sears also asserts that perfect balance of the various prostaglandin series can be achieved by following a diet in which protein, carbohydrate and fat are maintained in certain strict proportions. This is a highly simplistic view of the complex interactions on the prostaglandin pathway, one which does not take into account individual requirements for macro and micro nutrients, nor of imbalances that may be caused by nutritional deficiencies, environmental stress or genetic defects. Like all systems in the body, the many eicosanoids work together in an array of loops and feedback mechanisms of infinite complexity. Furthermore, liver and eggs are both highly nutritious foods. Liver supplies DGLA, a precursor of the Series 1 prostaglandins, and both liver and eggs supply DHA, an important nutrient for the brain and nervous system. Arachadonic acid found in butter and eggs is also an important constituent of cell membranes.

The Series 2 prostaglandins do indeed play a role in swelling and inflammation at sites of injury. This is not at all a “bad” effect, but an important protective mechanism—the body’s way of immobilizing the affected site to prevent further injury and facilitate healing. Series 2 prostaglandins also seem to play a role in inducing birth, in regulating temperature, in lowering blood pressure, and in the regulation of platelet aggregation and clotting.

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relationships between thromboxanes and prostacyclins of Series 2 (TXA2 and PGI2) with prostaglandins PGE1 of Series 1.14 For example, TXA2 seems to be essential for the release of calcium from the cells, while PGI2 inhibits release of calcium.

....
He notes that a variety of diseases can be explained in terms of imbalance between Series 1 and Series 2 prostaglandins. Over-synthesis of Series 2 prostaglandins encourages thrombosis; inhibition of overall prostaglandin syntheses can elevate blood pressure, and paradoxically, increase serum cholesterol
  • series 3 mitigates extreme reactions from series 2

Formation

The omega-6 pathway begins with double-unsaturated linoleic acid (LA) found mainly in seed oils. It is desaturated by the action of a desaturating enzyme, delta-6 desaturase (D6D), resulting in an 18-carbon, triple-unsaturated fatty acid called gamma-linolenic acid, GLA. (GLA differs from the 18-carbon triple-unsaturated alpha-linolenic acid in that the unsaturated carbon double bonds are in different places along the carbon chain.) An elongase enzyme then adds two more carbon atoms to GLA, taking us another step along the prostaglandin pathway to form a 20-carbon triple-unsaturated fatty acid called dihomo-gamma-linolenic acid (DGLA). DGLA forms the root of the Series 1 prostaglandins such as PGE1, PGF1a, and PGD1, and thromboxanes such as TXA1

DGLA is then transformed into 20-carbon quadruple-unsaturated arachidonic acid (AA), which is the root or precursor of the Series 2 eicosanoids. The Series 2 family includes a number of prostaglandins such as pge2 pgf2a and pgd2 ,prostacyclins such as pgI2, thromboxanes such as TXA2, leukotrienes and lipoxins.

Series 3 prostaglandins are produced on another pathway entirely, one that begins with triple unsaturated alpha-linolenic acid, found in seed oils of northern origin, like flax. This essential fatty acid is desaturated twice and elongated once to produce eicosapentaenoic acid (EPA), a 20-carbon fatty acid with five double bonds. EPA is the root substance of the Series 3 family that includes the prostaglandins such as PGE3, PGH3 and PGI3, thromboxanes such as TXA3 and leukotrienes. EPA is then further elongated and desaturated to produce docosahexaeonic acid (DHA) a 22-carbon fatty acid with six double bonds. DHA is found plentifully in the brain and is in fact essential for the development and function of the brain. DHA also acts as a storage molecule. It can be shortened and resaturated to produce EPA and the Series 3 eicosanoids.


Disseases, precautions

  • biggest issue is the blockage of production by inhibition of delta-6 desaturase (D6D)

{@weston}

One of the most common blocks in the prostaglandin chain involves delta-6 desaturase (D6D), the first step in the production of prostaglandins from essential fatty acids. When action of this enzyme is blocked, so is the entire pathway. This vital enzyme is inhibited first and foremost by trans fatty acids found in margarine, shortening and hydrogenated fats.

excess omega-6 fatty acids from modern commercial vegetable oils inhibit the pathway that leads to the Series 3 group. This is because both pathways begin with desaturation by the same delta-6 desaturase enzymes. Too much omega-6 in the diet “uses up” the delta-6 desaturase enzymes needed for the omega-3 pathway

Deficiencies of biotin, vitamin E, protein, zinc, B12 and B6 all interfere with the action of delta-6 desaturase and other enzymes involved in prostaglandin production.4 B12 is found only in animal foods. B6 is also found chiefly in animal foods. It is highly sensitive to heat. Best sources are raw dairy products, raw fish and raw meat. Zinc absorption is inhibited by phytic acid in whole grains and legumes, particularly soy, that have not been properly prepared. Best sources of zinc are animal foods—red meat, organ meats and some sea foods such as oysters

Alcohol consumption interferes with D6D, as does malnutrition and overeating—so moderation is the key to tripping lightly down the prostaglandin pathway

There is some evidence that an excess of oleic acid (found chiefly in olive oil and nuts) may inhibit prostaglandin production.5 Even consumption of essential fatty acids should be restricted to about 4% of the diet. Excess of EFA’s, especially omega-6 EFA’s, can cause problems with both pathways. Excess consumption of sugar also interferes with the desaturating enzymes.

Diabetes, poor pituitary function and low thyroid function are synonymous with altered and inhibited D6D function.6 These ailments are often treated with evening primrose, borage or black current oils, which contain GLA, the Series 1 precursor. Dietary GLA can be used when production is blocked by defective D6D action.

Diseases caused by altered D6D function include diabetes, alcoholism, cancer, premature aging, high cholesterol, Crohn’s disease, cirrhosis of the liver, eczema, PMS, noncancerous breast disease, Sjogren’s syndrome, scleroderma, ulcerative colitis and irritable bowel syndrome.

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Kidney disease as well as hyperthyroidism are associated with inadequate amounts of PGE1. TXA2 synthesis seems to be deficient in cases of ulcerative colitis, leaving to an overproduction of other prostaglandins.

Massive overproduction of certain prostaglandins seems to be involved in rheumatoid arthritis. A failure of TXA2 production, with concurrent excess production of other prostaglandins, leads to an increased susceptibility to cell mutation and hence to cancer. PGE1 deficiency seems to be involved in psoriasis and schizophrenia. On the other hand, manic behavior is associated with higher PGE1 production rates than normal. Depression is associated with elevation of TXA2 synthesis.

Various types of muscular dystrophy are associated with accumulation of calcium in the cells, due to reduced TXA2 production. Deficient TXA2 formation may also be involved in multiple sclerosis. Migraine headaches with accompanying gastrointestinal disturbances can be explained by increased prostaglandin production, particularly PGE1.

Historical Diet Perspective

{@weston}

The modern diet contains large amounts of omega-6 fatty acids compared to that of a generation ago, because high omega-6 oils from soy, corn, cottonseed and safflower have been introduced into the food supply. They are used to make hydrogenated fats and as a replacement for traditional fats and oils such as olive oil, butter, coconut oil, goose fat and lard. The modern diet is also deficient in omega-3 fatty acids compared to that of a generation ago because modern farming methods have the effect of increasing the amounts of omega-6 and oleic acid in vegetables, fruits, fish, eggs, grains and legumes, while decreasing the amount of valuable triple unsaturated omega-3. A good way to put omega-3 fatty acids back into the diet is to add a small amount of flax oil, rich in linolenic acid, to salad dressing.

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In India, milk products provide AA and shorter chain fatty acids while insects provide the longer chain fatty acids of the omega-3 chain. Fish, pork and coconut oil provide all the necessary fatty acids in the Polynesian diet; American Indians valued fish, bear fat and oil of the evening primrose plant. Traditional combinations of rich foods, therefore, need not be avoided. They provide factors that open both lanes of the prostaglandin pathway, creating a wide and open highway to skip along for renewed vitality and vibrant health.

Interesting

The desaturase enzyme systems do not work well in infants. This is why mammalian milk is rich in long chain fatty acids of both pathways {@weston}

The action of many drugs can be explained by their ability to stimulate or interfere with Series 1 and Series 2 prostaglandin production. Aspirin and steroids inhibit TXA2 activity and therefore reduce swelling; Lithium inhibits PGE1 which seems to be elevated in manic-depressive disorders. Melatonin, amantadine and colchicine (used to treat gout) activate TXA2.

Diet Notes

  • one egg a day is sufficient to ward of mental faculty loss {@weston}
Under optimum conditions, adults can make both DHA and EPA out of linolenic acid, the omega-3 essential fatty acid. But conditions are rarely optimal. Lack of many nutrients can inhibit the desaturating enzymes (D6D and D5D) that make this conversion, including deficiencies of protein, zinc, biotin, vitamin E, vitamin B6 and vitamin B12. Consumption of sugar, trans fatty acids and overconsumption of commercial vegetable oils, high in omega-6 fatty acids, also inhibits these enzymes. There is some evidence that an excess of oleic acid (found chiefly in olive oil and nuts) may inhibit prostaglandin production. On the other hand, saturated fats, especially lauric acid found in coconut oil, improve the body’s production of DHA and EPA.

!

Some population groups that have been largely carnivorous for generations, such as the Eskimo and Irish seacoast peoples, also lack these enzymes. Fish liver oils and organ meats are a must for these “obligate carnivores,” otherwise their prostaglandin pathways are largely dysfunctional.  This is why certain groups so quickly degenerate into alcoholism and other chronic diseases when they no longer have access to sea foods and organ meats found traditionally in their diets. Once again, cod liver oil with its rich cargo of EPA and DHA is the supplement of choice for people whose ancestors consumed large amounts of sea food and organ meats.

References

Default quote : {@weston}

@:weston
see files Tripping Lightly Down the Prostaglandin Pathways – The Weston A. Price Foundation.html | https://www.westonaprice.org/health-topics/making-it-practical/tripping-lightly-down-the-prostaglandin-pathways/