Answering the Fish or Flax Question

Essential fatty acids are making news with claims they benefit a range of conditions from asthma to Zellweger syndrome. Although provocative, much of the evidence is circumstantial and indirect, thus diminishing confidence in the purported benefits. There is, however, solid and compelling evidence supporting the benefit of omega-3 fatty acids—particularly those found in fish oils, eicosapentaenoic acid and docosahexaenoic acid—in cardiovascular disease prevention. The good-fat/bad-fat discussion often confuses consumers, though. So retailers should be able to answer the following questions when it comes to omega-3s.

What Are Omega-3 Fatty Acids And What Are Good Dietary Sources?
Chemically, omega-3 fatty acids are long chains of carbon atoms (18 to 22, if you're curious) with three to six double bonds (unsaturation sites) in the chain. All are polyunsaturated fatty acids, and are called omega-3s because the first double bond is on the third carbon atom counting from the end of the fatty acid molecule (the omega carbon). N-3 means the same thing, but instead of calling the last carbon omega, it is called the nth carbon. The terms long-chain and short-chain omega-3 fatty acids generally refer to EPA/DHA and alpha-linolenic acid, respectively.

EPA and DHA are found almost exclusively in seafood because they are synthesized by microscopic single-celled organisms at the base of the marine food chain. Generally, the oilier the fish, the more omega-3 fatty acids are present. Some fungal and algal DHA sources have been discovered, cultivated and commercialized primarily to supply the neonatal/infant formula industry with a non-fish omega-3 source. In the future, fungal and algal sources of EPA may be commercially available.

ALA, on the other hand, is synthesized in plant chloroplasts and is found in leaves and some seed oils. The richest, most readily available plant-oil source is flaxseed (or linseed) oil, which contains about 55 percent ALA by weight. Other sources are camelina, chia and perilla oils. Of the commonly used vegetable oils, canola and soybean are reasonably good sources. Certain nuts, primarily walnuts, contain some ALA.

What Is The Difference Between Fish Oil-Derived EPA/DHA And Plant Oil-Derived ALA? Can ALA Substitute For EPA/DHA?
EPA, DHA and ALA have structural differences, and, therefore, differ in their metabolism and ultimate health effects. The metabolites of EPA are well known and include eicosanoids, such as the 3-series prostaglandins, prostacyclins and thromboxanes, and the 5-series leukotrienes.¹ These EPA metabolites are generally less active than the proinflammatory and prothrombotic metabolites derived from arachidonic acid, EPA's omega-6 cousin. Because omega-3 and omega-6 fatty acids compete for conversion into these important metabolites, dietary intake levels determine tissue levels. And because the American diet is awash in omega-6 fatty acids, the best approach is to increase omega-3 and decrease omega-6 intakes.

ALA's only known essential role is to serve as a precursor to EPA and DHA. Although one study reported conversions of up to 15 percent,2 most researchers believe adults can only convert a small amount of ALA to EPA/DHA (perhaps less than 1 percent).3^,4 A primary reason why ALA is so poorly converted to the longer-chain EPA and DHA is because it is mostly used for energy, and thus rapidly removed from the blood, whereas EPA and DHA are not.

Is There Good Evidence Omega-3 Fatty Acids Have Health Benefits? Does ALA Have Different Effects?
The evidence is strong for EPA and DHA, but spotty for ALA. Although population studies (both worldwide and within the United States) are consistent with a cardioprotective effect of both marine5-8 and plant omega-3 oils,9^,10^,11 the former are also supported by compelling supplementation studies,12^,13,14 whereas such studies are generally lacking for ALA. Comparing populations with low versus high blood levels of marine omega-3 fatty acids, the risk for death from cardiovascular disease can be as much as 90 percent lower in the latter group.5^,6 But this association does not prove causation. In other words, because high blood levels of omega-3 fatty acids are associated with reduced risk for coronary heart disease does not prove omega-3 fatty acids are responsible. The kind of study that shows causation is a randomized, controlled trial.

There are two such studies with EPA/DHA:

In the Diet and Reinfarction Trial (DART), about 1,000 British heart patients were advised to eat two servings of oily fish per week or take fish oil capsules for two years.12 The other groups were asked to increase their fiber intake, alter their fat intake or to not change their eating habits. At the end of the study, 29 percent fewer people had died in the group advised to eat fish than in a similar group not given the advice. The primary weaknesses of this study are that the actual intake of EPA and DHA was not determined, but it was estimated to be about 600 mg to 900 mg per day, and that the observed protection cannot be unambiguously attributed to EPA/DHA alone. A long-term follow-up study with remaining survivors from the DART revealed that long-term dietary modifications—increasing fatty fish intake or fish oil capsule supplementation—does not reduce risk of cardiac death.15 This suggests the salutary effects of increased EPA/DHA intake are short-lived or are exerted only acutely.

In the GISSI-Prevention study, more than 2,800 Italian heart attack survivors were given purified EPA/DHA in capsule form and asked to take one per day for 3.5 years.^14,16 Each capsule provided 850 mg of EPA/DHA in roughly equal amounts. As in the DART, death rate from any cause was reduced by more than 25 percent, and sudden deaths (presumably from a second heart attack) dropped by more than 45 percent compared with a similar number of patients not given omega-3 oils. However, the cardioprotective effects of the EPA/DHA supplement manifested most prominently in the first nine months after a heart attack, with protection tapering off as the study progressed. Additionally, no benefit of EPA/DHA was noted for preventing a nonfatal secondary heart attack. These two studies, especially the latter, point directly to EPA/DHA as the agents responsible for the cardiovascular health benefit.

Similar studies have been attempted with ALA but they have not shown the same benefit, and researchers aren't sure why. It could be that ALA is ineffective, that too few patients were studied or that other extenuating circumstances obscured the true benefit. For example, in a study from Norway, more than 6,500 men in their 50s were given flaxseed oil supplements providing 5.5 g of ALA per day for one year.¹⁷ There was no cardiovascular benefit found compared with a similar group given sunflower seed oil, which contains virtually no ALA. Here ALA's failure could be that Norwegian diets already contain so much EPA and DHA that there was nothing left for ALA to do.

In another study, ALA supplementation (2.9 g per day from 20 ml of mustard seed oil) was compared with fish oil supplementation (1.8 g per day) in 360 patients admitted to an Indian hospital for suspected heart attacks.18 Although both fish oil and ALA reduced total cardiac events, the reduction was statistically significant only with the former. Here, the number of patients studied may have been too small to confidently detect a beneficial effect from ALA.

Finally, in the Lyon Heart Study, an increase in dietary ALA (from canola-based margarines) was just one of several diet modifications that together resulted in reduced heart attack risk.19 In this study, like the DART group encouraged to eat more fatty fish, it is impossible to unambiguously conclude ALA afforded the benefit when so many other things changed at the same time. (Study participants also ate less saturated fat and cholesterol and more fruits and vegetables.) So although there are suggestions from population studies that ALA may be beneficial, direct proof is lacking. Support for EPA and DHA, however, is stronger.

Why Are Omega-3 Fatty Acids Good For You?
A definitive answer is still unknown. Almost all the studies exploring mechanistics have used far greater doses of omega-3 oils than were used in the GISSI and DART studies. Doses of 3 g to more than 20 g of EPA/DHA have been examined for effects on blood lipids (notably triglycerides), platelet function (blood thinning), blood pressure, blood vessel flexibility and inflammation.20 In many of these studies, the marine omega-3 oils proved beneficial. There have been very few studies of the biological effects of the low intakes (less than 1 g per day) used in these major trials, so we don't know if the mechanisms proposed based on high-dose studies played any role in saving lives.

What Are The Recommended Intakes Of ALA, EPA And DHA?
The American Heart Association's nutrition committee recently published a scientific statement regarding omega-3 fatty acids, heart disease and stroke.20 After reviewing the literature, the committee made three recommendations:

For patients with diagnosed coronary heart disease, the AHA recommends "about 1 g of EPA/DHA per day." While preferring oily fish as the source, the AHA acknowledges many people either cannot or will not eat enough fish to meet this target. Accordingly, an EPA/DHA supplement could be considered with a health care provider's input.

For patients without diagnosed heart disease, the AHA recommends at least two meals of oily fish per week and the inclusion of oils and foods rich in ALA .

For patients who need to reduce serum triglyceride levels, the AHA recommends a higher dose of EPA/DHA, 2 g to 4 g a day. This would, of course, be done under medical supervision.

How Clean Are Encapsulated Oils?
With all the recent press about mercury toxicity of fish, it's natural to question fish oil capsule purity with respect to mercury or other environmental toxins such as PCBs and dioxins. Mercury can indeed bioconcentrate in fish at the top of the marine food chain, a fact that prompted the Food and Drug Administration to issue an advisory regarding four species of fish in particular: king mackerel, shark, swordfish and tile fish (also know as golden bass or golden snapper). Because fetuses and breast-fed infants are at highest potential risk for mercury toxicity, the FDA's advice to avoid such fish is directed primarily to pregnant (or wanting to be so) women and nursing mothers.

Mercury is not found in fish oil supplements because mercury (actually methyl mercury, the toxic form) is water-, not oil-soluble.²¹ When oil is extracted from fish, mercury (and lead, cadmium and other heavy metals) stay behind in the fish meal. (For information on the methyl mercury content of selected fish, visit www.cfsan.fda.gov/~frf/sea-mehg.html.) Organic pollutants are another matter. These oil-soluble compounds can find their way, via the marine food chain, into fish oils.²² Consequently, they can be detected in some fish oil products, most often cod liver oil. Fortunately, most supplements use fish oil concentrates derived from fish muscles rather than livers. Oil from muscle tissue contains significantly fewer pollutants.

Also, a more highly concentrated omega-3 fatty acid means lower amounts of chemicals are present. This is because more chemical processing is required to concentrate EPA and DHA, and such processing removes more pollutants.

The Irish equivalent of the FDA recently examined the extent of fish oil product contamination (visit www.fsai.ie/press_releases/130302.htm). Although it was able, with highly sensitive analytical methods, to detect a variety of industrial compounds in fish oil products, the agency concluded that when taken according to manufacturers' instructions, the products, even the cod liver oil, would not pose a health risk. As an aside, virtually all the meats and other animal products we eat also contain traces of these compounds. Whether and to what extent they are harmful is a matter of much speculation.

How Much Is Enough?
Although it is important to try to eat recommended amounts of omega-3 fatty acids, it is difficult to know how much you're actually getting. Fish have variable amounts of fatty acids. The levels in capsules are currently not regulated, thus label claims may or may not be true. And beyond an accurate measure of intake, each person has differences in digestion, absorption, tissue distribution and metabolism. Consequently, only a standardized blood test that measures red blood cell EPA and DHA levels can accurately measure intake.

Research Favors Fish Oils
Most Americans would do well to increase their intake of both plant- and marine-derived omega-3 fatty acids and to reduce their omega-6 fatty acid intake from vegetable oils. Getting more than the small amounts of EPA and DHA typically consumed in Western diets appears to reduce risk for death from heart attacks; whether ALA does the same is unknown. Recommended intakes of EPA and DHA are generally 0.5 g to 1 g per day. Recommended ALA intakes are about 1.5 g to 3 g per day. Foods are the optimal sources of these fatty acids, but capsules may also be used. Such capsules have virtually no heavy metal contaminants. Although traces of pesticide and herbicide residues are sometimes detectable in these oils, when taken at recommended levels they pose no health threat.

William S. Harris, Ph.D., is the Daniel Lauer/Missouri Professor in Metabolism and Vascular Research at the University of Missouri-Kansas City, and is co-director of the Lipid and Diabetes Research Center at the Mid America Heart Institute of St. Luke's Hospital in Kansas City. He is an internationally recognized expert in omega-3 fatty acids and cardiovascular health, with more than 20 years of research-related experience.

Harris owns Omegametrix LLC (www.omegametrix.com), a company that offers to the public analytical services for measuring red blood cell omega-3 levels.

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