2.34 Essential Fatty Acids & Eicosanoids

The two essential fatty acids are:

1. linoleic acid (omega-6)

2. alpha-linolenic (omega-3)

These fatty acids are essential because we can not synthesize them.  This is because we do not have an enzyme capable of adding a double bond (desaturating) beyond the omega-9 carbon counting from the alpha end (the omega-6 and 3 positions). The structures of the two essential fatty acids are shown below.

Figure 2.341 Linoleic acid1

Figure 2.342 Alpha-linolenic acid2

However, we do possess enzymes that can take the essential fatty acids, elongate them (add two carbons to them), and then further desaturate them (add double bonds) to other omega-6 and omega-3 fatty acids. Thus, there are 2 families of fatty acids that the majority of polyunsaturated fatty acids fit into as shown below.

Figure 2.343 Omega-3 and omega-6 fatty acids and eicosanoid production3

The same enzymes are used for both omega-6 and omega-3 fatty acids. However, we cannot convert omega-3 fatty acids to omega-6 fatty acids or omega-6 fatty acids to omega-3 fatty acids. Among these families, the omega-3 fatty acid, eicosapentaenoic acid (EPA), and the omega-6 fatty acids, dihomo gamma-linolenic acid and arachidonic acid (AA), are used to form compounds known as eicosanoids. These 20 carbon fatty acid derivatives are biologically active in the body (like hormones, but they act locally in the tissue they are produced). There are four classes of eicosanoids:

Prostaglandins (PG)

Prostacyclins (PC)

Thromboxanes (TX)

Leukotrienes (LT)

Some examples of eicosanoid structures are shown in the figure below:

Prostaglandin E1

Thromboxane A2

Leukotriene B4

Prostacyclin I2

Leukotriene E4

Figure 2.344 Eicosanoid structures4-8

The difference in the effects and outcomes of omega-6 and omega-3 fatty acid intake is primarily a result of the eicosanoids produced from them. Omega-6 fatty acid derived eicosanoids are more inflammatory than omega-3 fatty acid derived eicosanoids. As a result, omega-3 fatty acids are considered anti-inflammatory because replacing the more inflammatory omega-6 fatty acid derived eicosanoids with omega-3 fatty acid derived eicosanoids will decrease inflammation. As an example of the action of eicosanoids, aspirin works by inhibiting the enzymes cyclooxygenase (Cox)-1 and Cox-2. These enzymes convert arachidonic acid into inflammatory prostaglandins as shown below.

Figure 2.345 Aspirin inhibits Cox-1 and Cox-29

You have probably heard that you should get more omega-3s in your diet, and in general polyunsaturated fatty acids are considered healthy. However, since omega-3 fatty acids are competing for the same enzymes as omega-6 fatty acids, and because the omega-6 fatty acids are more inflammatory, consuming too many omega-6s is probably more detrimental than helpful. As a result, many people talk about the omega-3:omega-6 fatty acid ratio in people’s’ diets. For most Americans, the ratio is believed to be too high, at almost 10-20 times more omega-6 fatty acids than omega-3 fatty acids10. The table below shows good food sources of some selected omega-3 and omega-6 fatty acids.

Table 2.341 Good food sources of selected omega-3 and omega-6 fatty acids

Fatty Acid Good Food Sources
Linoleic Acid (LA, n-6) Safflower Oil, Corn Oil, Sunflower Oil
Arachidonic Acid (AA, n-6) Eggs, Meat
Alpha-Linolenic Acid (ALA, n-3) Walnuts, Flaxseed (linseed), Canola (rapeseed), and Soybean Oils
Eicosapentaenoic Acid (EPA, n-3) Fatty Fish & Fish Oils
Docosahexanoic Acid (DHA, n-3) Fatty Fish & Fish Oils

Even though Figure 2.343 illustrates the conversion of alpha-linolenic acid to EPA and DHA, this conversion is actually quite limited; 0.2-8% of ALA is converted to EPA and 0-4% of ALA is converted to DHA11. Thus, dietary consumption is the most effective way to get the longer chain fatty acids (EPA and DHA) in our bodies. It is less clear whether ALA consumption is as beneficial as EPA and DHA, but a recent study found it to be equally effective in decreasing blood triglyceride concentrations. In that study, DHA had the added positive benefit of increasing HDL12. These are all positive outcomes that are expected to reduce the risk of developing cardiovascular disease. However, there is evidence accumulating that there is not much cardiovascular benefit from taking fish oil supplements as described in the article below.

Web Link

Fish Oils Claims Not Supported By Research

Essential Fatty Acid Deficiency

Essential fatty acid deficiency is rare and unlikely to occur, but the symptoms are:

Growth retardation

Reproductive problems

Skin lesions

Neurological and visual problems

References & Links

1. http://en.wikipedia.org/wiki/File:LAnumbering.png

2. http://en.wikipedia.org/wiki/File:ALAnumbering.png

3. http://en.wikipedia.org/wiki/File:EFA_to_Eicosanoids.svg

4. http://en.wikipedia.org/wiki/File:Prostaglandin_E1.svg

5. http://en.wikipedia.org/wiki/File:Thromboxane_A2.png

6. http://en.wikipedia.org/wiki/File:Leukotriene_B4.svg

7. http://en.wikipedia.org/wiki/File:Prostaglandin_I2.png

8. http://en.wikipedia.org/wiki/File:Leukotriene_E4.svg

9. http://en.wikipedia.org/wiki/File:Eicosanoid_synthesis.svg

10. Simopoulos AP. (2008) The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med 233(6): 674.

11. Arterburn LM, Hall EB, Oken, H. (2006) Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 83(suppl) 1467.
12. Egert S, Kannenberg F, Somoza V, Erbersdobler H, Wahrburg U. (2009) Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr 139(5): 861.