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Prostaglandins: Cause and Cure of Inflammation

The author acknowledges that this topic is inherently laborious and complicated. Scientific research on the topic is quite comparatively recent on this topic. Very few cogent articles are available on the layman’s level. An attempt has been made to limit the amount of acronyms and huge Greek words. At any time, one can skip to the Summary Discussion Box at the end by using the on page scroller.

Prostaglandins are a member of a family of substances called eicosanoids. Other classical subgroups include thromboxanes (TX), leukotrienes (LT), eoxins (EX) and prostacyclins (PGI). Other non-classical subgroups including lipoxins are beyond the scope of this article. Eicosanoids are hormone like substances created in the body from fatty acids. Unlike hormones, eicosanoids are not produced by a specific organ, but created locally in a huge variety of cells. As of this article, nine primary Types of prostaglandins have been identified, designated by the letters A to I. Their actions and regulation include blood vessel permeability, blood pressure control, blood clotting, body temperature, muscle contraction and extension, control of some hormones, menstrual cycles, pregnancy and childbirth, inflammation and infection, stomach acid secretion, regulating formation of plaques in Alzheimer’s Disease, renal function, cancer and tumor control, and interocular pressure control. No doubt other functions with be discovered by future research.

Most Types of eicosanoids have been found to have three basic forms designated as Series with subscripts of 1, 2 and 3. Some older research refers to these forms as “Class”. The numbers of the subscripts 1, 2 and 3 refer to the number of available carbon double bonds in the molecule, which is called the degree of saturation. The actions of the subgroups Series 2 and Series 1 are commonly directly opposite to each other. Often Series 2 are labelled the “bad” or “antagonistic” prostaglandins. An example might be that PGE2 (Prostaglandin Type E, Series 2) contributes to inflammation, redness, swelling, pain, fever and blood clotting at the site on an injury as the primary step in healing. PGE1 prostaglandins do the opposite, which essentially is next in a healing cycle. Research is indicating that the Series 3 prostaglandins somehow moderate the production, balance and action of Series 2 versus Series 1 prostaglandins. Series 1 and Series 3 prostaglandins are commonly referred to as “good” or “beneficial” prostaglandins.

NSAIDs (Non Steroidal Anti Inflammatory Drug) such as aspirin, indomethacin and ibuprofen reduce inflammation by blocking the production of prostaglandins by inhibiting the cyclooxygenase enzymes (COX) used to produce prostaglandins. Unfortunately, they block the production of all prostaglandins.

Prostaglandins are short lived and cannot be stored. They are quickly modified to a non-functional form and excreted. They must be synthesized in nearby tissues and used locally. Prostaglandins occupy receptor sites on individual cells during their usage, and their action can vary with the exact receptor occupied, and with the exact amount of available prostaglandins. Individuals can have vast differences in the availability of prostaglandins, and in the ability to create the three Types of prostaglandins. This would appear to be determined less by Nature than by Nurture, meaning ones diet may make more difference than ones genes. Understand that nurture in this instance includes food, drink, medication, treatments and environment.

Prostaglandins are constructed from fatty acids. Each fatty acid is a chain of carbon molecules, and has a tip and a tail. The tip is a carboxylic acid group (-COOH) and is called the alpha end, or beginning. The carboxylic acid is a weak acid, and is the reason these lipids are called Fatty Acids. The tail is a methyl group (-CH3), and is designated as the omega end. In between the tip and the tail is usually an even number of carbon molecules. Some pairs of carbon atoms are linked with double bonds, and in that case only one hydrogen atoms is attached to either carbon atom. All other carbon atoms have a single bond between them, and each carbon is bonded to two hydrogen atoms.

The position of the first available double bond in relation to the tail determines the omega designation. Omega 3 means the third carbon molecule from the omega end or tail is the first available for bonding with other atoms or separation to form other complex molecules, which is how essential fatty acids are transformed to other fatty acids of varying lengths and functions. A shorthand designation is assigned to each fatty acid that names the number of carbon atoms (C??), then the number of available carbon double bonds (:?), and sometimes the omega designation (ω-?). Some articles use the letter “n” or “w” to indicate Omega.

Any fatty acid that has all the carbon bonds filled with two hydrogen atoms is called Saturated and has a shorthand designation with a zero after the colon (C??:0), indicating it has no available carbon double bonds. Lauric Acid, the primary constituent of coconut oil, has 12 carbons and is designated as C12:0. Saturated fatty acids are not prone to rancidity, as there are no carbon double bonds available to accept oxygen. They can however go rancid by being broken and/or through infection with microbes.

Any fatty acid that has any double carbon bonds is called Unsaturated and has a shorthand designation with a number after the colon (C??:#) indicating the number available carbon double bonds. A fatty acid that is unsaturated can go rancid, or oxidize. The molecule cleaves at a double bond, and oxygen atoms bond to the carbons with the normal double bonds. The oils all vary in the tendency to go rancid. Temperature, time, available oxygen and sunlight are the biggest factors. Oils with a larger percentage of mono-unsaturated fatty acids, and/or higher levels of vitamin E or other antioxidants, have a higher resistance to rancidity. Rancidity also occurs through hydrolitic action, meaning breaking apart trigliceride bonds; and through infection with microbes.

An essential concept is that each oil in nature is composed of a large combination of fatty acids with a varying number of carbon molecules. Saturated, polyunsaturated (PUFA), and mono-unsaturated (MUFA) fats and oils are so named when the highest percentage of the fatty acids present fit that classification. When one refers to olive oil as a mono-unsaturate, it is because about 75% of olive oil is Oleic acid (C18:1, 18 carbon atoms with 1 available carbon double bond). Oleic Acid is the 18 carbon member of the group of Omega 9 fatty acids (ω-9). A complete shorthand designation would be C18:1ω-9. Medium levels of mono-unsaturated fats help to control the production of antagonistic prostaglandins, high levels can slow all prostaglandin production.

All the fatty acids are stored in the body as Tissue Phospholipids. In addition to food sources, the fatty acids are sourced from these tissue phospholipids as needed to make the various eicosanoids. The regulation of this balance of food and tissue sources is critical to proper balances of the different series of prostaglandins.

Linoleic Acid and Series 1 Prostaglandins

Linoleic acid (C18:2) is the starting source for Series 1 and Series 2 prostaglandins. Series 1 prostaglandins have the following effects:

  • Prevent thrombosis, through disaggregation of platelets
  • Lower blood pressure
  • Open blood vessels and relieves angina pain
  • Slow down cholesterol production
  • Increase insulin efficiency
  • Prevent inflammation and controls arthritis
  • Control cell growth, including cancers and tumors
  • Improve nerve function and control pain
  • Improve T-cell function
  • Regulate calcium metabolism
  • Prevent release of Arachidonic acid from cells, which slows down Series 2 prostaglandins production

Linoleic acid is dominant in the plant based oils. Linoleic Acid often designated as (LA), and is the 18 carbon member of the group of Omega 6 fatty acids (ω-6). A complete shorthand designation would be C18:2ω-6. Although most of the Linoleic acid in a diet is plant sourced, animal products contain some Linoleic acid as LA is accumulated and stored through their diet.

To make Series 1 prostaglandins, Linoleic acid must be transformed into Gamma Linolenic acid (GLA) by an enzyme called Delta-6 Desaturase (D6D). A complete shorthand designation for GLA would be C18:3ω-6. In enzyme language, a desaturase removes the two hydrogens from two adjacent carbon atoms and creates a double bond between them. In other words, a desaturase creates another unsaturated point on a fatty acid carbon chain. This same D6D enzyme is also used in the starting process of making Series 3 prostaglandins. GLA must be processed by using an elongase enzyme which, like it sounds, works to enlongate a fatty acid chain by adding 2 more hydrocarbon segments (-CH2).

This converts GLA into Dihomo Gamma Linolenic acid (DGLA)(C20:3ω-6). At this chemical juncture, DGLA can be transformed into Arachindonic acid as a precursor to Series 2 prostaglandins, or into Series 1 prostaglandins using cyclooxygenase enzymes (COX).

There a very few sources of naturally occurring GLA in any diet. These include evening primrose oil (~ 8-11%), borage seed oil (~ 15-17%), hemp seed oil (~ 1%) and black currant seed oil (~ 14-17%). Series 3 prostaglandins mitigate which Series of prostaglandin is eventually made from GLA. However it should be seen that the overall lack of Series 1 prostaglandins is due to a decreasing ability for a body to produce Gamma Linolenic acid (GLA). This can be countered by adding a GLA source to the diet.

The following factors inhibit the production of Gamma Linolenic acid. Some work by inhibiting the D6D enzyme that converts Linoleic acid to GLA, which also limits Series 3 prostaglandin production:

  • Aging Process
  • Diets containing high levels of saturated fats
  • Diets containing levels over 5% of essential fatty acids (EFA)
  • Diets containing high levels of Omega 6 fats, as they use up so much D6D enzyme
  • Processed, rancid, and hydrogenated vegetable oils, which block the D6D enzyme
  • Lack of biotin, vitamin E, zinc, magnesium and vitamins B6 and B12, condition interferes with D6D and other enzymes
  • Medium to high sugar and/or alcohol consumption, interfere with D6D enzyme
  • Diabetes, poor pituitary function and low thyroid function, interfere with D6D enzyme
  • Malnutrition or overeating, interfere with D6D and other enzymes
  • Viral infections, cancer and diabetes
  • Radiation, including nuclear byproduct exposure, and UV from excessive sunlight
  • Stress and some mental illnesses

Arachidonic Acid and Series 2 Prostaglandins

Arachidonic acid (C20:4ω-6) is the direct source for Series 2 prostaglandins via cyclooxygenase enzymes (COX). Series 2 prostaglandins have the following effects:

  • Initiate blood clotting by aggregating platelets
  • Increase blood pressure by constricting blood vessels
  • Induce labor
  • Involved in menstrual cycles
  • Lower insulin efficiency
  • Promote inflammation
  • Promote cell growth, including tumors
  • Help initiate immune response
  • Regulate calcium metabolism
  • Increase release of arachidonic acid from cells

The body creates Arachidonic acid from Linoleic acid, but mostly it is sourced from meat and dairy products, butter, animal fats, organ meats, egg yolks and some seaweeds. Arachidonic Acid often designated as (AA), and is the 20 carbon member of the group of Omega 6 fatty acids (ω-6). The complete shorthand designation is C20:4ω-6.

Arachidonic acid is known as a “conditionally essential fatty acid”. AA does become essential if there is a deficiency in Linoleic acid or if one has a lowered ability to convert Linoleic acid to Arachidonic acid. The central nervous system, liver and skeleton require AA for proper function, and levels are about 10% to 20% of a body’s tissue fatty acids, highest in the nervous system. Higher levels of Arachidonic acid are better utilized with higher levels of activity, as they help the body recover from heavy workouts. So Arachidonic acid itself is not the issue, problems occur when too much Series 2 prostaglandins are made from it.

Linolenic Acid and Series 3 Prostaglandins

Linolenic acid (C18:3) is the initial precursor for Series 3 prostaglandins. Series 3 prostaglandins have the following effects:

  • Protect against heart attack and stroke
  • Control arthritis, lupus and other auto immune issues
  • Control asthma
  • Modulate the production of Series 2 vs. Series 1 prostaglandins
  • Prevent release of Arachidonic acid from cells, which slows down Series 2 prostaglandins production

Linolenic acid is sourced mostly from fish oil and other marine products. Linolenic Acid often designated as Alpha Linolenic Acid (ALA), and is the 18 carbon member of the group of Omega 3 fatty acids (ω-3). In some articles who don’t want to speak Greek, it is also known as LNA. The complete shorthand designation is written as C18:3ω-3. Linolenic Acid must be converted in three steps starting with Delta-6 Desaturase (D6D) to Eicosapentaenoic Acid (EPA) (20:5ω-3). Eicosapentaenoic Acid is thankfully referred to as EPA (20:5ω-3), and is getting to be another household dietary acronym. EPA is then converted using cyclooxygenase enzymes (COX) to make Series 3 Prostaglandins.

Another Fatty acid in the Omega 3 pathway to be aware of is Docosahexaenoic acid, or DHA (22:6ω-3). DHA is the other beneficial Omega 3 fatty acid found in marine sourced oils, organ meats and organic egg yolks. DHA is a bit like a storage unit, since the pathway from EPA to DHA can be reversed, and Series 3 prostaglandins can therefore be made from DHA. DHA is absolutely essential for brain development in infants, and is plentiful in human breast milk.

Diets containing high levels of Omega 6 fats will lower production of Series 3 prostaglandins, as the Omega 6 fats use up so much of the available D6D enzyme. Series 3 prostaglandins are created at a much slower rate than either Series 1 or Series 2 prostaglandins. Think of Type 3 prostaglandins most important function as being the regulator of whether one is producing more anatagonistic or more beneficial prostaglandins.

The Final Step

The modification of Dihomo Gamma Linolenic acid (DGLA), Arachidonic acid (AA) and Eicosapentaenoic Acid (EPA) to the appropriate eicosanoids involves initial changes by cyclooxygenase and lipoxygenase enzymes, and often many further processes that are beyond the scope of this article. Oxidation inside a cell is potentially dangerous, so these processes are carefully and highly regulated. The constituents created by the break down pathways during normal metabolism of eicosanoids can also have side effects and reactions.

Prostagladin Pathways from Omega 3 and Omega 6 Fatty Acids

A Summary Discussion

Prostagladins are the body’s primary defense against inflammation, auto immune diseases and tumor growth. Along with other eicosanoids, they control a huge variety of bodily functions. Produced locally, they have autocrine and paracrine functions, meaning that they work on the same cells or nearby cells from their production sites.

Basically, all eicosanoids, including prostaglandins, are created starting with 18 carbon chain fatty acids that get modified and extended to 20 carbon chain versions, then carefully modified and oxidized into complex hormone-like substances. A proper balance of the fatty acids is necessary to achieve a proper balance of prostaglandins.

Many diseases. diets, anti-inflammatory treatments and other drugs scuttle the body’s ability to create the beneficial prostaglandins needed to control inflammation. Most work by stopping the action of the D6D enzyme. The D6D enzyme is responsible for the beginning step of the conversion of Linoleic acid and Linolenic acid to prostagladins. To restate more obviously, anti-inflammatory drugs (NSAID’s) that stop the production of the inflammatory Series 2 prostaglandins also stop the production of beneficial Series 1 and Series 3 prostaglandins.

Long term diseases, eating habits and drugs may lead to dire side effects, as well as the inability to heal oneself by maintaining proper beneficial prostaglandin levels. Understand that inflammation is a body’s primary method of starting a healing process, but inflammation is also key in auto immune issues such as arthritis and lupus, as well as other diseases and infections. The failure to adequately control inflammation creates the long term degradations found in such diseases.

Many dietary trends are often low in the ingredients to make adequate beneficial prostaglandins. There are many complex pathways involved in producing beneficial prostaglandins, and a myriad of ways in which these pathways can be disturbed or stopped. Those who monitor ongoing research about the ideal ratios of the different Omega fatty acids should easily recognize that the prostaglandin balance is key to those health benefits.

Over the last century or so, food in general has had a diminishing trend for Omega 3 fatty acids. Animals are raised commonly on feed stocks rather devoid of Omega 3’s. Maintaining animal health often involves drugs and treatments that block fatty acid conversions. In the effort to reduce calories by reducing fat, and using it for other purposes, beneficial fats are reduced.

Plants are grown using pesticides and fertilizers that can reduce their Omega 3 content. Using unrefined oil is essential for health. Often oils are processed in a manner that strips them of beneficial components. Commercial oil refining removes lecithin, chlorophyl, many free fatty acids, phosphotides, minerals, Beta carotene, flavinoids and vitamin E. Then preservatives are generally added. During the deodorization part of the process, the temperature reaches 240 degrees and beyond, which can damage remaining beneficial fatty acids.

The process of hydrogenation to increase shelf life and resistance to temperature (think margarine and shortening) yields highly unhealthy fats and trans fats which are not only marginally or not at all usable for body processes and components, but also block the action of beneficial fatty acids. Common frying and deep frying techniques damage oils that are rich in essential fatty acids, so most common frying oils contain only trace amounts of Omega 3 fatty acids.

Omega 6 to Omega 3 ratios between 2:1 and 3:1 are accepted as ideal. At the risk of contradicting growing public consciousness about Omega ratios, it should be mentioned that, within reasonable boundaries, the real issue is not the ratios. Ultimately it is the amount of available Omega 3 fatty acids. For most, this means taking marine or flax supplements supplying about a gram a day. For those in need of healing from arthritis, cancer, lupus, infections or inflammation; the solution might be to ramp up those supplements to 2 to 3 grams per day per 100 lbs of body mass.

Of great importance is the general lack of Gamma Linolenic Acid (GLA) from which Series 1 beneficial prostaglandins are made. One can supplement a direct source of GLA of around 1/2 gram per day of borage seed oil or black currant seed oil, 1 gram per day of evening primrose oil, or 10 grams per day of hemp seed oil per 100 lbs of body mass. Adding GLA directly to the diet is usually not necessary long term and can be ramped back down once the symptoms of an issue are diminished.

Proper consumption of certain saturated fatty acids improves prostaglandin balance. Saturated fats, especially Lauric acid found in coconut oil, have been proven to assist in the production of beneficial prostaglandins by enhancing production and storage of EPA and DHA.

Please understand that this recommendation is based on a rather simplistic view of the complex interactions of prostaglandins and their production. It is a good generality, but does not account for individual genetic defects, mental illnesses, rare diseases, or nutritional deficiencies.

Personal review and research of prostaglandins is difficult. The vast majority of available information concentrates solely on the Series 2 prostaglandins responsible for detrimental effects. Indeed most available articles and definitions only include Series 2 information. This is not a problem, except in that it makes it harder to evaluate the complex interaction of prostaglandins, and eicosanoids in general.

In all the information and experiments available about fats and oils, seldom are the topics of oil contamination, quality and condition addressed. Since oils and fats can contain damaging pesticides, drugs and other chemical compounds, the wise choice of sources is paramount to long term health.

A large industry in the pharmacological equivalents of eicosanoids, mostly prostaglandins and leukotrienes, has developed and is burgeoning. Over time, further research and better integration of the many forms of medicine will help render a more usable body of information on prostaglandins.

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