Chapter 9
Supplements for Control of Eicosanoids
As with other areas where we can use supplements to "rebalance" certain aspects of metabolism, the same is true of eicosanoids. Remember from previous chapters that eicosanoids are hormonelike cellular messengers that can be proinflammatory or anti-inflammatory in nature. Simply by eating more of the right types of fats (anti-inflammatory omega-3s) and fewer of the wrong type (proinflammatory omega-6s), we shift the balance away from "bad" eicosanoids and toward "good" eicosanoids, and in doing so, we reduce overall levels of inflammation throughout the body.
Essential Fatty Acids
The term "essential fatty acids" refers to two fatty acids, linoleic acid and linolenic acid, that our bodies cannot synthesize and thus which must be consumed in the diet. (Vitamins and minerals are also termed "essential" because the human body cannot make them and therefore must consume them.) These essential fatty acids are needed for the production of compounds known as eicosanoids, which help regulate inflammation, blood clotting, blood pressure, heart rate, immune response, and a wide variety of other biological processes.
Linoleic acid is a polyunsaturated fatty acid with eighteen carbon atoms and two double bonds. It is considered an "omega-6," or "n-6," fatty acid because the first of its double bonds occurs at the sixth carbon from the omega end. It is also referred to as C18:2n6 (meaning eighteen carbons, two double bonds, with the first double bond at n-6 position). It is found in vegetable and nut oils such as sunflower, safflower, corn, soy, and peanut oil. Most Americans get adequate levels of these omega-6 oils in their diets, due to a high consumption of vegetable oil-based margarine, salad dressings, and mayonnaise.
Linolenic acid, or alpha-linolenic acid, is also an eighteen-carbon polyunsaturated fatty acid, but it is classified as an "omega-3," or "n-3," fatty acid because its first double bond (of three) is located at the third carbon from the omega end. It is also known as C18:3n3 (meaning eighteen carbons, three double bonds, with the first double bond at the n-3 position). Good dietary sources for linolenic acid are flaxseed oil (51 percent linolenic acid), soy oil (7 percent), walnuts (7 percent), and canola oil (9 percent), as well as margarine derived from canola oil. For example, a tablespoon of canola oil or canola oil margarine provides about 1 gram of linolenic acid.
If you think back to the original type of diet early humans relied upon for survival- the so-called caveman diet-it provided a much more balanced mix of n-3 and n-6 fatty acids. Over the last century, modern diets have come to rely heavily on fats derived from vegetable oils (n-6)-bringing the ratio of n-6 to n-3 fatty acids from the caveman's ratio of about 1:1 to the modern-day range of 20-30:1. The unbalanced intake of n-6 fatty acids (high) to n-3 fatty acids (low) sets the stage for increases in blood viscosity (and tendency of blood to clot), vasoconstriction (and elevated blood pressure), and inflammatory processes (involved in everything from heart health to pain levels). Yikes!
Fatty acids of the n-3 variety, however, have opposing biological effects to those of the n-6 fatty acids, meaning that a higher intake of n-3 oils can deliver anti-inflammatory, antithrombotic (clot-preventing), and vasodilatory (blood pressure-lowering) effects that can lead to benefits in terms of heart disease, hypertension, diabetes, and a wide variety of inflammatory conditions such as rheumatoid arthritis and ulcerative colitis.
In the body, linoleic acid (n-6) is metabolized to arachidonic acid, a precursor to specific "bad" eicosanoids that can promote vasoconstriction and elevated blood pressure. Linolenic acid (n-3), however, is metabolized in the body to EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). EPA serves as the precursor to prostaglandin E3, which may have vasodilatory properties on blood vessels, effects that can counteract the vasoconstriction caused by n-6 fatty acids. DHA has been associated with optimal brain development in infants.
Recent studies have shown that consumption of linolenic acid and other n-3 fatty acids offers wide-ranging anti-inflammatory benefits. This effect is thought to be mediated through the synthesis of EPA and DHA. Fish oils contain large amounts of both EPA and DHA, and the majority of studies in this area have used various concentrations of fish oil supplements to demonstrate the health benefits of these essential fatty acids. For example, 1 gram of menhaden oil (a common source) provides about 300 mg of these fatty acids. EPA is known to induce an antithrombotic (clot-preventing) effect through its inhibition of platelet cyclooxygenase (which converts arachidonic acid to thromboxane A2, two compounds that are highly inflammatory) and the "less sticky" platelets that result. Fish oil, with its high content of EPA and DHA, may also protect against heart disease through an anti-inflammatory effect (via reduced cytokine production and/or increased nitric oxide production in the endothelium).
There is also some evidence that omega-3 fatty acids from fish oil and flaxseed may help improve insulin sensitivity (thus reducing glycation) and reduce the perception of stress (thus decreasing cortisol exposure). A recent expert scientific advisory board at the National Institutes of Health highlighted the importance of a balanced intake of n-6 and n-3 fatty acids to reduce the adverse effects of elevated (inflammatory) arachidonic acid, a metabolic product of n-6 metabolism. The committee recommended a reduction in the intake of n-6 fatty acids (linoleic acid) and an increase in n-3 (linolenic acid, DHA, EPA) intake.
No serious adverse side effects should be expected from regular consumption of essential fatty acid supplements, whether from fish oil or other common oil supplements (see below). Due to the tendency of n-3 fatty acids to reduce platelet aggregation (i.e., "thin" the blood), increased bleeding times can occur in some individuals.
The best dietary sources of omega-3 fatty acids are fish such as trout, tuna, salmon, mackerel, herring, and sardines, which all contain about 1-2 grams of n-3 oils per three- or four-ounce serving. A minimum of 4-5 grams of linoleic acid (but no more than 6-7 grams) and 2-3 grams of linolenic acid are recommended per day. Supplements of linoleic acid (n-6) are typically not needed, whereas linolenic acid (n-3) supplements (4-10 g/day) and/or concentrated EPA/DHA supplements (400-1,000 mg/day) are recommended to support cardiovascular health. Total DHA/EPA intake should approach about 1 gram per day, evenly split between the two sources.
The most common supplemental source of essential fatty acids is fish oil-a good source of the omega-3 fatty acids. Other oils, such as flaxseed, borage seed, and evening primrose, are rich sources of essential fatty acids but typically do not provide the high levels of concentrated EPA/DHA found in many fish oil supplements. The highest-quality fish oil supplements should provide 18-30 percent EPA and 12-20 percent DHA. The higher the EPA/DHA content, the better (but also the more expensive).
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