In my last two posts I talked about the importance of ω3 polyunsaturated fatty acids (PUFAs). In this post I want to focus on their role as precursors for a group of hormone-like substances collectively known as eicosanoids. The information presented here is largely taken from a recent review article on dietary lipids in inflammatory disorders like cardiovascular disease (1). Some of that material is also summarized on a couple of U.S. National Institutes of Health (NIH) websites (1).

Our bodies make these eicosanoids from two C-20 polyunsaturated fatty acids, the ω3 PUFA eicosapentaenoic acid (EPA) and the ω6 PUFA arachidonic acid (AA). Eicosanoids regulate important physiological functions like inflammation (prostaglandins), blood clotting (thromboxanes), and the immune response (leukotrienes). These are obviously vital defense mechanisms, but when they get out of hand the result is tissue damage and disease.

What could cause these defense mechanisms go awry? Physiological responses regulated by the ω6 PUFA derivatives are usually much stronger and more dangerous than the hormonal effects of EPA-derived prostaglandins, thromboxanes or leukotrienes. Imbalances in the ω3/ω6 ratios therefore have serious health consequences. The higher the ω6/ω3 eicosanoid ratio, the greater the danger of overreaction and disorders like chronic inflammation.

What determines the eicosanoid ω3/ω6 ratio? We can make neither ω3 nor ω6 PUFAs; they have to come from our diets. The ω3/ω6 eicosanoid ratio in our fat stores simply reflects the dietary mix of ω3 and ω6 polyunsaturated fatty acids, This in turn determines the ω3/ω6 ratio of PUFAs incorporated into cell membrane phospholipids, the precursors for eicosanoid synthesis.

Our bodies don′t seem to preferentially make either ω3 or ω6 eicosanoids. Phospholipid-bound ω3 and ω6 PUFAs are equally likely to be released and used as precursors. The elongation of shorter PUFAs to the C-20 fatty acids — linoleic acid to AA and α-linolenic acid to EPA — is catalized by the same enzymes. Other enzymes convert both EPA and AA to eicosanoids, and the ω3- and ω6-derived eicosanoids compete for the same receptors.

There are some quantitative differences in conversion rates and receptor binding between ω3 and ω6 eicosanoids. Nevertheless, the ω3/ω6 eicosanoid ratios are largely determined by the mix of phospholipid-bound ω3 and ω6 PUFAs, and therefore ultimately by the dietary ω3/ω6 mix. There is a clear correlation between the phospholipid PUFA fraction belonging to the ω6 series and death from cardiovascular disease — the higher the ω6 percentage, the greater the death toll (1).

What causes this ω3/ω6 PUFA imbalance in our diets? It is largely due to the excessive consumption of vegetable oils. Canola oil has the least unfavourable ω3/ω6 ratio at about 1:2. That ratio for corn oil is about 1:9, and the other commonly used oils aren′t any better. You can find a table of PUFA compositions for the more common cooking oils on one of the NIH websites quoted in the reference list (1).

Rebalancing the ω3/ω6 polyunsaturated fatty acid mix really requires both a reduction in dietary ω6 PUFA intake and an increase in ω3 PUFA consumption. Given the accumulated excess of ω6 PUFAs in our tissues, taking fish oils is much more effective than adding α-linolenic acid from sources like flax seeds. The conversion from the C-18 PUFA α-linolenic acid to EPA is simply too inefficient; preformed EPA itself is 15 times more effective at raising EPA levels than α-linolenic acid (2).

Compensating for excess ω6 fatty acids is by no means the only role of ω3 fatty acids, nor are imbalances in eicosanoids solely responsible for cardiovascular disease. There can be little doubt, however, that imbalances in dietary polyunsaturated fatty acid intake contribute to heart disease. This connection is both firmly established clinically and physiologically plausible.

So, Eat fatty fish or take EPA/DHA supplements! It is a simple and effective way to reduce your risk of cardiovascular disease and other inflammatory disorders.

Sources:

1. Lands B. A critique of paradoxes in current advice on dietary lipids. Progr Lipid Res 2008;47:77-106. See also
   http://dx.doi.org/10.1016/j.plipres.2007.12.001 [Free Abstract]
   http://ods.od.nih.gov/eicosanoids/ and
   http://efaeducation.nih.gov/
2. Brenna JT, Salem Jr. N, Sinclair AJ, Cunnane SC. α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukotrienes Essential Fatty Acids 2009;80:85-91.
   http://www.plefa.com/article/S0952-3278(09)00016-7/abstract [Free Abstract]