Omega 3 and Omega 6 Pathways - Inflammation and Asthma

(back to EFA)

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Drug VS Non-drug approaches to inflammation

To understand why inflammation is increased in asthma, how asthma drugs work, and why the RAINS Study approach may be effective, it is necessary to go into a little chemistry. We have tried to take a simple step-by-step approach for those who are new to the subject.

The principle difference between our complementary approach, and a strictly drug approach, lies in the importance of providing sufficient nutrients for the body to properly reduce inflammation. The nutrients necessary, just for the following pathways to function properly are:

• essential fatty acids (omega-3 and omega-6, in balance),
• zinc,
• magnesium,
• pyroxidine (vitamin B6),
• niacin (vitamin B3), and
• ascorbic acid (vitamin C).

Deficiencies in any one of these nutrients can lead to excess inflammation and result in an increase in asthma symptoms.

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Omega-3 and Omega-6 Pathways

If you have a chemistry background, the following explanation may be old hat to you.

Conversely, however, if this is your first look at omega-3 and omega-6 metabolism, at first glance, the following figures and explanations may seem a little complicated. 

By taking your time, in the next few minutes you will learn, step-by-step: 

• The composition of fatty acids,
• How omega-3 fats can reduce inflammation in asthma,
• How too much of omega-6 fats and/or too little of omega-3 fats, can create inflammation,
• How enzymes are responsible for the conversion of fats,
• How nutritional deficiencies can indirectly create inflammation in asthma,
• Why omega-3/omega-6 balance in the body is important for asthmatics 

BEFORE YOU START - A tip to make this lesson easier for you - Keep the line you're reading scrolled to the top of the page. Try it, and scroll up until this is the line is at the top of the page now, and don't forget to keep scrolling as you read each line.

As you can see, in the above figure, the newly formed Stearidonic Acid, has had an extra double bond created in the carbon chain. 

The number of carbon atoms (18) hasn't changed. However, the number of hydrogen atoms has been reduced from 29 to 27. Another way of looking at it, is that the carbon chain is now less saturated with hydrogen atoms. In other words the chain has been de-saturated of two hydrogen atoms. 

In this example the "desaturation" of hydrogen atoms that has happened is the result of the enzyme delta-6-desaturase. Can you now see how this enzyme gets the desaturase part of it's name?

Now, can you guess what saturated fat means?

That's right, a carbon chain that is completely full of hydrogen atoms, with no spaces for any more hydrogen atoms. These saturated fatty acid chains can vary from 3-20 carbon atoms. 

If a fat is "hydrogenated", in a manufacturing process, what do you think they've done? If you guessed that they filled up the fat with hydrogen atoms, you're right.

You can  probably now guess what partially-hydrogenated fat means.

So, what does hydrogenation of fat mean to you? 

Well, the more empty spaces there are in a fatty acid chain, the more biologically active and alive these fats are.

Saturated fats on the other hand are biologically inactive, which means for all our purposes, they are dead. 

That's why you can leave saturated fat products on the shelf without them "going bad" or rancid. When you're a dead fat, there's no "going bad."

We have been sold on the idea of using dead, hydrogenated, saturated fats because they have a long, economical, shelf life. 

Live, unsaturated fatty acids on the other hand do "go bad" or rancid after awhile. 

This is actually good news, because these are the kind of fats you want in your diet. 

Live fats. And, which do you think your living cells prefer - live or dead fats?

In the next few slides, you'll now see how the enzymes delta-6-desaturase, delta-5-desaturase, elongase, cyclo-oxygenase and oxygenase alter the structure of alpha-linolenic acid (omega-3) into the beneficial, anti-inflammatory prostaglandins – PGE3 series prostaglandins - which reduce inflammation in the body. (Don't worry, we'll take you through, step-by-step as you scroll down).

The following figure shows the conversion pathway of alpha-linolenic acid (1). Note the nutrients that are essential to the enzymes, which make the conversions possible. Without enough of these nutrients these conversions cannot happen. The consequences of this will become clear in a few moments.

Alpha-linolenic acid (1) is converted into stearidonic acid (4) by the enzyme delta-6-desaturase (2). Delta-6-desaturase requires sufficient B6, magnesium and zinc(3) to perform it's duties.

Stearidonic acid (4) is then converted to eicosatetraenoic acid (6) by the enzyme elongase (5).(scroll down)

Eicosatetraenoic acid (6) is then converted to eicosapentaenoic acid (EPA)(9) by the enzyme delta-5-desaturase. Delta-5-desaturase is dependent upon the nutrients vitamin C, niacin and zinc to properly perform it's functions. Unfortunately asthmatics have been shown to be deficient in each of these three nutrients. (See Vitamin C & B3 Deficiencies and  Zinc Deficiencies)

Delta-5-desaturase also prefers to convert EPA into anti-inflammatory prostaglandins of the PGE3 series. This is good news for asthmatics, as this would help to reduce inflammation.

The following figure illustrates that conversion of EPA (9) into anti-inflammatory prostaglandins of the PGE3 series by way of (10) cyclo-oxygenase (COX). 

Cyclo-oxygenase and oxygenase conversion of EPA

Unfortunately, the use of COX inhibitors blocks this conversion, and therefore blocks the benefit to the cells of the PGE3 series anti-inflammatory prostaglandins (11). COX inhibitors are targeted at the Omega 6 pathway, which we will now look at.

Dihomogamma linolenic acid (4) is now converted by delta-5-desaturase to either Arachidonic Acid (AA)(11) or Series 1 Prostaglandins (8). As you can see,  the preferred pathway(7) for omega-6 fatty acids is to the Series 1, anti-inflammatory prostaglandins (8) PGE1.  PGE1 relaxes blood vessels, improving circulation, lowering blood pressure, and even relieving angina. It decreases inflammation response, helping to control arthritis and asthma.  It also regulates calcium metabolism which is helpful in asthma.  PGE1 also improves the functioning of T-cells in our immune system, which destroy foreign molecules and cells that can aggravate asthma symptoms. Finally, PGE1 prevents the release of inflammation causing arachidonic acid from our cell membranes.    Now, this is important to understand: When there is a deficiency of omega-3 fatty acids in the diet, the delta-5-desaturase enzyme (9), rather than being used to convert EPA into Series 3 (anti-inflammatory prostaglandins in the Omega 3 pathway), will begin to convert more DGLA (6) into arachidonic acid (11) and the inflammatory Series 2 Prostaglandins (13). COX-2 enzyme inhibitors reduce inflammation by blocking the final step (12) in the arachidonic acid to Series 2 Prostaglandin pathway.  This is a good news/bad news story, because while they block the production of inflammatory prostaglandins, they also block the production of the anti-inflammatory Series 3 Prostaglandins in the Omega-3 Pathways. The following diagram shows where top asthma drugs interfere with the arachadonic acid pathway: The following is a list of some commonly prescribed NSAIDs: Generic Name Brand Name Traditional NSAIDS Acetylsalicylic Acid (ASA) Diclofenac Ibuprofen Naproxen Aspirin* Voltaren Advil, Motrin* Naprosyn, Anaprox COX-2 Inhibitors Celecoxib Rofecoxib   While drugs designed to interfere with the Arachadonic pathways do give relief, they ignore potential unknown side-effects resulting from interference in both omega-3 and omega-6 pathways. This gives further clarity to the importance of the balance of omega-3 to omega-6 fatty acids and the specific nutrients required in the diet for the enzymes necessary for the proper conversions. If essential fatty acids are properly balanced, the body is in a state of homeostasis, leaning towards a state of non-inflammation. To the degree that balance shifts, towards excessive omega-6 in the diet, we see an increase in inflammatory conditions like asthma and arthritis. To reach that homeostasis, we believe in the restoration of the entire pathways through sufficient essential fatty acid intake, of both omega-3 and omega-6, and enzyme support provided through supplementation of nutrients to make up for any existing deficiencies. Inflammatory conditions, due to imbalanced ratios of essential fatty acids, are presented in a number of other studies.