Wednesday, December 23, 2009

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, like the essential vitamins and minerals, must be consumed in the diet. These essential fatty acids are needed for the production of prostaglandins and eicosanoids – which help regulate blood-clotting, blood pressure, heart rate, immune response and a wide variety of other biological processes.

Linoleic acid is a polyunsaturated fatty acid with 18 carbon atoms and two double bonds. Linoleic acid 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 18 carbons, 2 double bonds, first double bond at the 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 18-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 at the third carbon from the omega end. It is also known as C18:3n3 (meaning 18 carbons, 3 double bonds, first double bond at the n-3 position). There are 3 major types of omega-3 fatty acids that are consumed in foods and utilized by the body: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA can be converted into EPA and DHA in the body. Good dietary sources of ALA are flaxseed oil (51% linolenic acid), canola oil (9%) and walnuts (7%) 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.

Omega-3 fatty acids are generally found to reduce inflammation and thus to have a positive impact on heart disease, arthritis, and other inflammatory conditions such as allergies, asthma, inflammatory bowel disease and others. The existing data for a health benefit of omega-3 fatty acids is particularly strong for a reduced risk of heart disease.


Over the last century, modern diets have come to rely heavily on fats derived from “high n-6” vegetable oils (sunflower, safflower, corn, etc) – bringing the ratio of n-6 to n-3 fatty acids from an estimated “Paleolithic” ratio of 1:1 to the modern-day range of 20-30:1. The unbalanced intake of high n-6 fatty acids and low n-3 fatty acids sets the stage for increases in blood viscosity, vasoconstriction, and generalized inflammation involving everything from heart health to pain levels.

Fatty acids of the n-3 variety, however, have opposing biological effects to the n-6 fatty acids – meaning that a higher intake of n-3 oils can deliver anti-inflammatory, anti-thrombotic and vasodilatory 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.

The most common supplemental sources of essential fatty acids are 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% EPA and 12%-20% DHA. The higher the EPA/DHA content, the better (but also more expensive).

Although GLA supplements are widely available as extracts of evening primrose (EPO) and borage seed, their claims of benefit in reducing menopausal hot flashes, PMS symptoms (breast tenderness and irritability), and inflammatory conditions such as eczema, asthma, allergies, and rheumatoid arthritis are generally not well-supported by objective scientific literature. The data in this area are very mixed and the response to GLA supplementation may be very individual based on initial GLA levels.

The very best evidence for a beneficial health effect of essential fatty acid supplementation exists for the use of fish oil supplements (EPA/DHA) in the reduction in cardiovascular disease risk – prompting the Food and Drug Administration to issue a “qualified health claim” for omega-3 supplements indicating that “The scientific evidence about whether omega-3 fatty acids may reduce the risk of coronary heart disease (CHD) is suggestive, but not conclusive. Studies in the general population have looked at diets containing fish and it is not known whether diets or omega-3 fatty acids in fish may have a possible effect on a reduced risk of CHD. It is not known what effect omega-3 fatty acids may or may not have on risk of CHD in the general population.” Such claims language is permitted on foods or supplements provided that the product does not recommend a daily intake exceeding 3 grams per day of EPA and DHA (which, for the majority of standard fish oil supplements would be in the range of 9-10 grams/day of fish oil).

Scientific support

In the body, linoleic acid (n-6) is metabolized in the body to gamma-linoleic acid (GLA) and then to arachidonic acid – a precursor to specific “bad” eicosanoids which can promote vasoconstriction and elevated blood pressure. Gamma-linoleic acid (GLA), however, while also a fatty acid of the n-6 variety, when taken as a dietary supplement (typically from evening primrose oil, borage seed oil, and black currant seed oil) may be converted largely to dihomogamma-linoleic acid (DGLA), which is known to compete with arachidonic acid (typically found in egg yolks and meat) for conversion into proinflammatory eicosanoids, making GLA (via DGLA) a potential anti-inflammatory fatty acid in conditions such as dermatitis (Thijs et al. 2000, van Gool et al. 2003), periodontis (Rosenstein et al. 2003), rheumatoid arthritis (Leventhal et al. 1994) and inflammatory respiratory disorders (Gadek et al. 1999). Despite this potential anti-inflammatory effect of GLA, the scientific evidence supporting the anti-inflammatory effects of omega-3 fatty acids is much stronger (Blommers et al. 2002, Hederos and Berg et al. 1996, Henz et al. 2000). For example, linolenic acid (n-3) 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 which can counteract the vasoconstriction caused by n-6 fatty acids (Honstra et al. 1990, Kurlandsky et al. 1994).

Recent studies have shown consumption of linolenic acid and other n-3 fatty acids to offer protection against heart disease and heart attacks. This effect is thought to be mediated through the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish oils contains 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, one gram of menhaden oil (a common fish source) provides about 300mg 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) and the “less-sticky” platelets that result. Fish oil, and 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).

Flaxseed, a rich plant source of omega-3 fatty acids, has been shown to lower both systolic and diastolic blood pressure (1-2 tablespoons daily). Epidemiological studies have shown that subjects with high intakes of linolenic acid (n-3) have been shown to have a 50% reduced risk of heart disease - which may be partly due to beneficial effects on blood pressure, cholesterol levels, blood clotting and heart rhythm. Indeed, omega-3 fatty acids are known to reduce thromboxane activity, which could explain the benefits of omega-3’s in reducing platelet aggregation (blood clotting), blood vessel constriction, and a variety of inflammatory conditions such as dermatitis (Bjorneboe et al. 1989) and rheumatoid arthritis (Cleland et al. 1988).

There is also some evidence that omega-3 fatty acids from fish oil and flaxseed may help improve insulin sensitivity, modulate lipid metabolism and combat both mild depression and Attention Deficit and Hyperactivity Disorder (ADHD). Although the data is far from clear, it is known that omega-3 fatty acids are concentrated in the brain and that children and adults suffering from depression and/or ADHD typically show sub-optimal blood levels of essential fatty acids. In addition, population studies suggest that a high consumption of fish (rich in omega-3’s) may be related to a lower risk of depression, including postpartum depression. Mothers pass large amounts of essential fatty acids to their babies during the last 3 months of fetal brain development and via breast milk – so much that new mothers have only half the normal blood levels of omega-3 fatty acids and nursing mothers may have even lower levels.

A number of scientific studies suggest that diets high in omega-3 oils may protect against the development of diseases such as heart disease, attention deficit disorder, arthritis, colitis and other inflammatory diseases (Hawkes et al. 2002, Volker et al. 2001). It has been convincingly shown that omega-3 fatty acids can reduce triglyceride levels in the blood as well as blood pressure (Kestin et al. 1990). The effects of omega-3s on cholesterol levels, however, are inconsistent and may require excessive doses of fish oil to be effective. In rare instances, high dose fish oil supplements may even increase serum cholesterol levels in genetically predisposed individuals.

A major heart protective effect of omega-3 oil is its effect in reducing the “stickiness” of platelets in the blood – thus reducing the likelihood for formation of blood clots. Regular consumption of diets high in fish is clearly linked to a reduced incidence of heart attacks. In some studies, it even appears that the real importance isn’t how much fish you eat – but that you eat it at all. In other words, eating fish once a week appears to be just as effective as eating it 3 or 4 times each week.

The strongest data supporting a heart health benefit of omega-3 fatty acid consumption come from intervention trials with coronary heart disease (CHD) as the endpoint. These studies have ranged in length from 1 year to 3.5 years and in size from 223 people in one study location to 11,324 people in 172 separate centers and have reported significant reductions in CHD risk with increased consumption of omega-3 fatty acids, predominantly EPA and DHA at approximately 800-900mg/day (Burr et al. 1994, GISSI 1999, von Schacky et al. 1999, Singh et al. 1997). Although some of these studies reported an increase in LDL levels, others reported a decrease in LDL and the majority reported no change. In particular, the longest (3.5 years) and largest (n = 11,324) trial found no change in LDL cholesterol, while also reporting a 15% decrease in relative risk of CHD (GISSI 1999). In prospective studies of fish intake (as opposed to intake of fish oil supplements), there is a strong decreased risk of CHD with increasing consumption of fish that may be related to the drop in serum triglyceride levels associated with increasing omega-3 fatty acid intake (Albert et al. 1998, Guallar et al. 1995, Layne et al. 1996, Morris et al. 1995).

Safety / Dosage

No serious adverse side effects should be expected from regular consumption of essential fatty acid supplements or omega-3 oils – whether from fish oil or other common oil supplements (see below). Fish oil is considered by FDA to be GRAS (generally recognized as safe), but due to the tendency of n-3 fatty acids to reduce platelet aggregation (“thin” the blood), increased bleeding times can occur in some individuals (Lund et al. 1999) and doses of EPA/DHA above 3grams per day should be avoided (9-10 grams of most standard fish oils providing 30% omega-3 fatty acids). Other potential safety concerns of high-dose omega-3 fatty acid consumption, since discounted, have included increased oxidation of cell membranes rich in omega-3’s, increased blood levels of LDL cholesterol, and reduced glycemic control among diabetics (Pedersen et al. 2003, Ramirez-Tortosa et al. 1999, Wander and Du et al. 2000).

ALA (alpha-linolenic acid, one of the omega-3 fatty acids) is found in flaxseeds, flaxseed oil, canola oil, soybeans and soybean oil. The best dietary sources of EPA and DHA are cold-water fish such as trout, tuna, salmon, mackerel, herring, and sardines, which all contain about 1-2 grams of n-3 oils per 3-4 ounce serving. The Food and Nutrition Board of the National Academy of Sciences has established an Adequate Intake (AI) of total n-6 fatty acids (primarily linoleic acid) of 11-17 grams/day and total n-3 fatty acids (primarily alpha-linolenic acid) of 1.1 – 1.6 grams/day for adults (an approximate 10:1 ratio of n-6 to n-3 fatty acids). A 4-ounce portion of salmon may contain 900mg of omega-3 fatty acids, while a 4-ounce portion of Atlantic mackerel provides 2.6g of EPA and DHA.

Supplements of linoleic acid (n-6) are typically not needed, whereas linolenic acid (n-3) supplements (2-4g/d) and/or concentrated EPA/DHA supplements (400-1000mg/d) are recommended to support cardiovascular health. According to the International Society for the Study of Fatty Acids and Lipids (ISSFAL), total EPA/DHA intake should be a minimum of 220mg/day of each and should approach about 1 gram per day – about evenly split between the two. Pregnant and lactating women are advised to increase their DHA intake somewhat so that they consume at least 300mg of DHA daily to ensure adequate brain development in their growing babies. When using flax as a concentrated source of essential fatty acids, a typical dose is 1-2 tablespoons per day.

Dosing recommendations for flax seed are 1 Tbsp per day – or up to 3000mg/day from capsules as a dietary source of ALA). Diabetics may lose the ability to convert ALA to EPA and DHA, and thus may need to supplement with fish oil.

GLA supplement recommendations are in the range of 1000-15000mg/day or up to 3000mg of EPO. Levels of GLA above 3000mg/day may lead to higher conversion to AA rather than to the blocking effect of DGLA.


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EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

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