Essential Omega-3 and Omega-6 Fatty Acids

  • Higher omega-3 fatty acid blood levels particularly the long-chain variety of omega-3 fatty acids (EPA and DHA) have  cardiovascular protective benefits.
  • Higher dietary intakes of the plant based omega-3 called alpha linoleic acid (ALA) have been associated with an approximate 20% lower risk of fatal heart disease.
  • Individual blood level response to omega-3 supplements can vary considerably.

Plant-based nutrition typically provides us with polyunsaturated fatty acids (also called PUFAs) that include omega-3 and omega-6s. Both of these plant based PUFAs are important for good health and are considered essential fatty acids.

Essential fatty acids

Essential fatty acids means the body cannot make them and must be supplied by nutrition. Along with omega-3 fatty acids, omega-6 fatty acids play a crucial role in normal growth and development and brain health.  A healthy diet contains a balance of omega-3 and omega-6 fatty acids. Quite importantly, the typical American diet tends to contain a low amount of omega-3 fatty acids and 14 to 25 times more omega-6 fatty acids.

Flaxseeds, walnuts, soy foods, pumpkin seeds, and canola (rapeseed) oil are good sources of polyunsaturated fats that include the essential omega-3 called alpha linolenic acid (ALA). The most common omega-6 polyunsaturated fatty acids (PUFA) is linoleic acid (LA) also derived from vegetable oils and is abundant (comprising over half by weight) of safflower, sunflower, and corn and poppy seed oils.

Two types of omega-3s

There are two major types of omega-3 fatty acids in our diets one type from plants and the other from marine sources. Alpha-linolenic acid (abbreviated as ALA) is found in some vegetable oils, such as soybean, rapeseed (canola), and flaxseed, walnuts and some green vegetables, such as Brussel sprouts, kale, spinach, and salad greens. The marine sources of omega-3s are found mostly in cold-water fish and consist of the two most biologically important omega-3s called: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids are polyunsaturated fatty acids that are essential nutrients for health. The human body is able to partially convert ALA (the plant-based omega-3) to EPA and EPA. Nevertheless, both vegetable and marine sources of omega-3 fatty acids have health benefits.

Omega-6 friend or foe?

The American Heart Association (AHA) supports an omega-6 PUFA intake of that makes up at least 5-10% of total calories. Higher consumption of linoleic acid (LA), an omega-6, has a number of health benefits. Increasing linoleic acid containing oils may help lower blood pressure and improve insulin resistance -the problem associated with prediabetes and diabetes and reduce the incidence of type 2 diabetes. However, there has been some controversy about omega-6 oils. A recent re-analysis of an old study (1966-1973) called the Sydney Diet Heart Study (British Medical Journal, 2013) raised health concerns about very high levels of the omega-6, linoleic acid (safflower oil margarine substitution for saturated fats) in a group of prior heart attack survivors. The study showed more harm in the group randomized to more omega-6 but the results are far from conclusive. The majority of those original participants  were active smokers (despite their recent heart attack) and smoking is known to oxidize linoleic acid.  Oxidized LA is a bad player and is the major fatty acid component of oxidized LDL-cholesterol and an increased amount of oxidized LDL-C can enhance the progression of atherosclerosis (hardening of the arteries) and increase “plaque instability” and heart attacks. The lack of benefit and evidence of harm with increased omega-6 fatty acids in the Sidney Diet Heart Study is believed by most experts to be far from conclusive. The results are considered confounded by smoking which is a strong oxidant. Most experts agree that there is insufficient evidence that health can be improved by reducing omega-6 but, on the other hand, there are well documented health benefits of increasing omega-3 fatty acids.

The ratio

There is also a belief that omega-6 fatty acids are pro-inflammatory and must be reduced to improve the omega-6 to omega-3 ratio. This ratio has been considered by some critical for optimized health. However, both of the essential omega-3 and omega-6 fatty acids have been scientifically proven to benefit cardiovascular health and any target ratio can obviously be influenced by changing the numerator -or the denominator. Therefore, amounts become irrelevant in ratios, so the use of ratios can obviously be misleading: is it too much omega-6 -or not enough omega-3? The use of the omega-6/omega-3 ratios to guide nutrition choices is not recommended. Omega-6 have pro-inflammatory properties and anti-inflammatory properties and a more reliable ratio looks at the more specific fish-derived omega-3 fatty acid called EPA (eicosapentanoic acid) and the omega-6 called arachidonic acid (AA). The EPA/AA ratio has much more credibility since clinical trial results show a higher ratio is associated with less heart disease and lower risk of sudden death.


Omega-3 fatty acids can exert heath benefits by way of multiple mechanisms. They can prevent cardiac electrical instability (arrhythmia), and lessen the risk of hardening of the arteries and its complications. These benefits are believed related to anti-inflammatory properties and anti-blood clotting mechanisms. In addition, omega-3’s can stimulate the release of a natural blood vessel dilating chemical called nitric oxide. Omega-3 fatty acids are required for numerous normal body functions, including building cell membranes in the brain and are associated with protection against heart disease and possibly stroke. Clinical studies are now ongoing in regard to benefits for such conditions including cancer, inflammatory bowel disease, and other autoimmune diseases such as lupus and rheumatoid arthritis. Some of the pivotal studies related to cardiovascular diseases the number one cause of death on the planet follows:

Clinical Trials

  • The Lyon Heart Study was the first clinical trial to demonstrate the beneficial effects of the Mediterranean diet in reducing heart disease compared the effectiveness of a Mediterranean diet enriched with the plant based omega-3 fatty acid called alpha linolenic acid (ALA) (supplied by a canola-enriched margarine) compared to those who received usual care with a “prudent” Western-type diet typically prescribed for heart health. The death rates from recurrent cardiovascular disease were significantly reduced in the group of patients with known coronary disease randomly assigned to consume a Mediterranean diet. Moreover, the Harvard School of Public Health’s Nurses Health Study found a 45% reduction in incident fatal heart attack associated with those with the highest compared to lowest amounts of alpha-linolenic acid.

There is positive evidence of higher omega-3 blood levels and associated lowest risk of cardiac arrest (sudden cardiac death). Higher omega-3 fatty acids blood levels compared to lower levels in healthy individuals aged 65 and older -without preexisting heart disease were associated with nearly a 30% lower risk of cardiovascular death including sudden death and with slower rates of cellular aging. (Mozaffarian D, et al. Plasma Phospholipid Long-Chain omega-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study. Annals of Internal Medicine 2013;158:515-25). In this study blood levels of EPA and DHA -the 2 main long-chain omega3s were associated with significant health benefits and decreased risk of cardiac arrest and provide biologic plausibility to maintaining higher omega3s (either by nutrition and/or supplement use).

  • The largest of the omega-3 outcome studies, the GISSI-P (GISSI-Prevention) trial originally reported in 1999 studied 1 gram of omega-3 supplementation in a group of heart attack victims and showed a very significant reduction in overall mortality, cardiac death and an impressive 45% reduction in sudden death rates over a 3.5-year period. Significant benefits of supplementation emerged within three to four months and were most notable in those patients with more significantly impaired heart function.
  • Results from the JELIS (Japanese Eicosapentaenoic Acid Lipid Intervention Study) in 2007 used 1.8 g/day of EPA and in a high risk group (only 20% had prior coronary disease unlike the GISSI-P study) and showed a reduction of combined cardiovascular events but no benefit in mortality or sudden death. This study did decrease “unstable” cardiac events leading many to consider a protective effect on hardening of the artery progression. Two more recent studies from 2010 in those with known coronary artery disease were “neutral” and did not show a decrease in cardiac events. Both the German OMEGA that studied 1 g/day omega-3 PUFAs and Alpha Omega trial that  used a margarine supplemented with low-dose EPA+DHA or ALA, EPA+DHA+ALA or a control margarine were both substantially underpowered and the results must be interpreted with caution.
  • In patients with preexisting hardening of the arteries (atherosclerosis) the UCSF Heart and Soul Study looked at higher blood levels of EPA+DHA (>3.6% of total fatty acids) and CV risk. Those with higher blood levels had a clinically important lower risk of all-cause death over nearly a 6-year period of follow-up.
  • The GISSI-HF (GISSI-Heart Failure) study was a large trial that looked at omega-3 PUFAs in a group of heart failure patients maximally treated with current standard of care therapy. The simple addition of a 1 gram of omega-3 supplement demonstrated a statistically significant reduction of all-cause death rate. This is considered clinically a very important finding and has led researchers to initiate further larger studies. Heart failure is a very common and serious condition and represents the number one reason for hospitalization in the USA for seniors. The ability to lower the death rates in heart failure may be an important advance.

Omega-3 fats in general have had favorable associations with various measures of health including a beneficial or effect on type 2 diabetes. A more recent prospective, population-based study looked at omega-3 blood levels and found that higher blood levels of omega-3s (a marker of fish intake) is linked to a lower long-term risk for type 2 diabetes. Those participants with the highest omega-3 intake lowered diabetes by 33% (Diabetes Care. 2014;37:189–196). There continues to be interest on measurements of the two major marine sources of omega-3s: EPA and DHA. Higher EPA blood levels were linked to lower cardiovascular disease risk in the JELIS study and in the Framingham Heart Study higher blood levels of DHA were linked to a nearly 50% less risk of dementia (Arch Neurol. 2006;63:1545-1550).

Fish and Omega-3s

EPA and DHA supplements could be considered in consultation with the physician especially if there is limited fish consumption. Higher fish intakes (up to and including 5 servings) have been associated with an approximate 40% lowering of coronary heart disease mortality based on epidemiological studies. Omega-3 fatty acids especially from marine sources have an important triglyceride lowering effect and are used therapeutically at higher doses (4 grams per day) with severely elevated triglycerides (>500mg/dL).


High concentrations of mercury, a neurotoxin can damage developing brains in fetuses, and can be found in some kinds of popular fish such as albacore “white” tuna (0.32 parts per million of mercury). Children under six can eat up to one 3-ounce portion a month; children from 6–12, two 4.5-ounce portions a month. Consider canned light tuna (0.12 parts per million of mercury) the better choice when buying canned tuna. Beware of “gourmet” or “tonno” labels which contain yellowfin tuna and can contain mercury levels comparable to canned white.

  • A healthier choice to consider is canned salmon (mostly sockeye or pink from Alaska) that is low in contaminants and high in heart-healthy omega-3s.

Other high mercury fish include the following: swordfish, shark, king mackerel, marlin, orange roughy and tilefish. Women of reproductive age and young children are advised to avoid these types of fish and limit overall consumption of all fish to no more than 12 ounces per week, according to the Food and Drug Administration, as it takes months for the body to rid itself of mercury. If you want more information about the levels in the various types of fish you eat, see the FDA food safety web site or the EPA Fish Advisory website.

The Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) consider five of the most commonly eaten fish that are low in mercury are: shrimp, canned light tuna, salmon, pollock, and catfish. When choosing your two meals of fish and shellfish, you may eat up to 6 ounces (one average meal) of albacore tuna per week. The American Heart Association recommends eating fatty fish at least twice a week because it is high in omega-3 fatty acids. Fatty varieties that are low in mercury include wild salmon, herring and sardines.

Controversy and a look at the details

Fish oil (omega-3s) studies have periodically been a source of controversy. A high profile and controversial meta-analysis (or collection of studies) found that omega-3s did not improve health and many believed this was the final nail in the coffin about omega3s . The basis of this negative finding was the appearance of a lack of statistical significance -that is the way science works. A critical review of the study design however tells another story. The study broke with tradition and demanded an unusually high statistical level for significance and defined the so-called “p-value” (a marker of statistical significance) at 0.006 (this means there is only a 0.6% chance the results were the result of chance).

The statistical hurdle (p value 0.006) was very controversial and not even close to the more commonly used level of significance (defined by a p value at 0.05)  If not for this statistical maneuver the results should have been reported that fish oil supplementation significantly reduced risk for cardiac death by 9% (relative risk reduction of 0.91; 95% CI, 0.85 to 0.98; p=0.01). (Rizos EC, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: A systematic review and meta-analysis. JAMA. 2012;308:1024-1033).

Men’s health and Omega-3s

A recent media storm followed a 2013 report by Brasky et al. in the J Natl Cancer Institute entitled, “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial” and had many men thinking twice about their omega-3 supplements.  This headlines did not accurately report the study design and findings. The study did not test the question of whether giving fish oil supplements (or eating more oily fish) increased prostate cancer risk but evaluated omega-3 blood levels -blood levels are related to intake, metabolism and genetics. Nevertheless, the differences of omega-3 blood levels between prostate cancer cases and controls were actually very small (a difference from 3.62 to 3.74) and still within the normal variation. Bottom line, the differences are considered of no clinical significance.

A more complete story about omega-3 and prostate cancer is found in a large 2010 study that analyzed multiple studies (a meta-analysis) reported a reduction in late stage or fatal cancer, but no overall relationship between prostate cancer and fish intake. A prior in 2001 study reported higher fish intake was associated with lower risk for prostate cancer incidence and death, and another in 2004 reported similar findings. (Terry Pet al. Fatty fish consumption and risk of prostate cancer. Lancet 2001;357:1764-6, Leitzmann MF, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 2004;80:204-16).

Reassuring is the fact that Japanese typically eat about 8 times more omega-3 fatty acids than Americans do and their blood levels are twice as high, and their prostate cancer risk is not higher but much lower than in the West. The lower 5th percentile of blood omega-3 fatty acids in the Japanese living in Japan is higher than the average levels in Americans -including Japanese Americans.

The randomized control studies do not support any harmful effect of omega-3 on cancer risk in general, and a 2012 review of omega-3 and prostate cancer concluded the higher your blood levels of omega-3s the lower the cancer risk. (Gerber M. Omega-3 fatty acids and cancers: a systematic update review of epidemiological studies. Br J Nutr 2012;107 Suppl 2:S228-S39.)


According to the AHA patients with documented heart disease should consume about 1 g of omega-3 per day of this essential fatty acid -preferably from oily fish. American’s have in general very low omega-3 levels and it is more likely that lower amounts of omega-3 and not too much omega-6 is a health concern. Higher omega-3 blood levels are associated with improved heart health but individual variability of blood level response to eating fish or taking supplements is possible and likely accounts for some mixed and misleading study results. Omega-3 studies that show significant benefits in heart health also show the benefit is correlated with the highest omega-3 blood levels.

Harris, WS. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Current Atherosclerosis Reports. 2006; 8(6):453-9

Itakura H, Yokoyama M, Matsuzaki M, et al. Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb. 2011;18:99-107.