Omega-3 Fish Oils: The Greatest Nutritional Health Discovery Since Vitamins, Part Three—The Basics of How EPA and DHA Bring Health Benefits

An Interview with Professor Jørn Dyerberg, M.D.

Written By:
Richard A. Passwater, Ph.D.
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Do all omega-3 fatty acids provide heart benefits? Does the ratio of EPA to DHA matter? Is EPA good for the heart while DHA is good for the brain? Does it matter if EPA and DHA are present as free fatty acids, triglycerides or ethyl esters? Several misconceptions have arisen over the years and some readers may be surprised at the answers to these questions.

We have been chatting with Dr. Jørn Dyerberg regarding his major discovery of omega-3 fatty acids in human health. In the June 2010 issue, Dr. Dyerberg recounted his expedition into Greenland to discover why these remote-living Eskimos had about only one-tenth the heart disease incidence of many Western Countries including the USA and Denmark. Last month, we discussed the detective work required to solve the scientific riddle. In this session, we will cover how EPA and DHA function and clarify several issues concerning omega-3 fatty acids in general.

 Jørn Dyerberg, M.D., professor and Dr. Med. Sc., has made several discoveries that elucidate many of the health benefits of omega-3 fish oils. Dr. Dyerberg made five scientific expeditions to Northwest Greenland in the 1970s examining the association between fish oil intake and coronary heart diseases in Eskimos. Dr. Dyerberg, who is Danish, hypothesized that the rarity of coronary heart disease among the Inuit could be due to the omega-3 fatty acids in their diet consisting largely of seal and cold-water oily fish. Together with his fellow researchers, he went on to elucidate the unique physiological effects of these fatty acids. His research opened new fields leading to thousands of health studies by many. His own research encompasses more than 350 scientific publications primarily concerning blood lipids, atherosclerosis, the blood coagulation system, omega-3 polyunsaturated fatty acids, trans-fatty acids and prostaglandins.

 In 2007, Dr. Dyerberg was honored by the American Heart Association in “Recognition of Outstanding Scientific Contribution for the Advancement of Heart Health Worldwide.” In 2008, he received the American Dietetic Association Foundation’s Edna and Robert Langholtz International Nutrition Award.

Passwater: Usually in science, when one question is answered, other questions are raised. You sought to uncover why Eskimos had only a fraction of the heart disease normally observed in Western Nations. You found a difference in EPA and DHA content between the blood of Eskimos and that of the Danes and North Americans. This raised the question: From where did these fats come? You were able to trace their origin to diet. This raised the question: What biochemical effects did they have? You verified that EPA and DHA had effects on cardiovascular health in terms of improved (longer) blood clotting times, improved blood lipid (triglycerides, cholesterol, etc.) levels and a better balance of prostaglandin (PG) formation. This raised several other questions. Is either EPA or DHA more important? Can other omega-3 fatty acids have similar biochemical effects? Can other fatty acids be converted into EPA and DHA in the body or are EPA and DHA themselves essential fatty acids?

Let’s start with the very basics of the concept that some types of fats are essential to life. At one time, fats were considered merely unessential sources of calories. Now, we understand that fats are important components of every cell and the many compounds made from fats are involved in controlling thousands of functions. We now recognize that a balance of omega-3 and omega-6 fats that is close to the balance of fats of the Paleolithic diets to which man has been exposed for many thousands of years is a better fit for our genetic makeup than the more recent agricultural diets and the modern fast-food diets.

The concepts of “vitamin F” and “essential fatty acids” were developed decades ago, but no one knew much else about the biochemistry of fatty acids. Drs. H.M. Evans (the discoverer of vitamin E in 1925) and George O. Burr demonstrated that fat-free diets impaired the growth and reproduction of laboratory animals in 1927 (1). They viewed this as a vital factor in fats along the lines of a vitamin and called this factor “vitamin F” at first. Drs. George O. Burr and Mildred M. Burr introduced the concept of essential fatty acids (EFAs) during the next two years (2). Specifically, linoleic acid (LA)—a C18: 2 omega-6 fatty acid that cannot be made in the body—was involved. The deficiency symptoms noted were basically scaly skin and an increased consumption of water. These symptoms were eliminated when LA was added to the fat-free diet. It wasn’t until about 1970 that it was realized that EFAs were critical to the retina. Now, EFAs are recognized as being essential to normal growth reproduction and good health.

Dr. Dyerberg, wasn’t that basically all that was known about EFAs when you found appreciable amounts of EPA and DHA in the blood of the Greenland Eskimos?

Dyerberg: Yes, at the time we made our original observations in Inuits, the essentiality of (omega-6) fatty acids was related only to these basic issues, and the focus was on linoleic acid. The omega-3 series was not considered and the discovery of derived products (as the prostaglandins) was in its initial state, and the relation of EPA and DHA deficiencies to increased Ischemic Heart Disease (IHD) was unknown. IHD is the medical term for reduced blood flow to the heart. Over the years, interest in the health benefits of consuming omega-3 fatty acids EPA and DHA has also been aimed at the intake of the EFA alpha-linolenic acid (ALA, 18: 3 n-3), which in other mammals can be converted into EPA and DHA. In man, however, it can only be converted to a small extent.

The focus of interest has in that respect been twofold: whether ALA has health benefits of its own and whether the conversion of ALA to longer-chained omega-3 fatty acids in humans is sufficient to produce desirable tissue levels of EPA and DHA.

The concept of “essential” polyunsaturated fatty acids (PUFAs) is a bit odd in a way, in that very few essential functions are known of the prime essential PUFAs linoleic acid (18: 2 n-6) and linolenic acid (18: 3 n-3). Linoleic acid has a function in the water barrier of the skin, but no essential functions are known related to linolenic acid. Their longer-chained derivatives, arachidonic acid (AA) (20: 4 n-6), EPA (20: 5 n-3) and DHA (22: 6 n-3), are truly the “essential” fatty acids when it comes to their function and effects in the body.

Passwater: The Institute of Medicine states, “ALA is not known to have any specific functions other than to serve as a precursor for synthesis of EPA and DHA” (3). Heart health involves more than the old concept of EFAs. What is important to heart health goes beyond growth and maintenance and the classical symptoms of EFA deficiency of scaly skin and thirst. Cardiovascular optimization involves the two long-chain omega-3 fatty acids, EPA and DHA, and their intermediary docosapentaenoic acid (DPA) (22: 5n-3). The only fatty acids for cardiovascular optimization are EPA and DHA. Let’s look at the basics of EPA and DHA.

We have mentioned earlier that the body is very inefficient in producing either EPA or DHA from the more common plant-based omega-3s such as ALA from flaxseed oils and a similar C18 omega-3 fatty acid from other plant oils and certain fish, stearidonic acid (SDA).

Animals do have enzymes that can add double bonds and lengthen the fatty acid (desaturation and elongation) in polyunsaturated fatty acids, but not after the omega-9 position in the fatty acid. (Plants can introduce new double bonds between an existing double bond and the terminal methyl group.) Animals can increase unsaturation to a very limited extent, but can’t change an omega 6 into an omega-3, nor can they make omega 6 or omega 3 fatty acids.

Dr. Dyerberg. Please elaborate on the ability for humans to make EPA and DHA and how does this relate to heart health?

Dyerberg: The body can form a small amount of EPA and DHA from ALA. However, this is inadequate for optimal cardiovascular health.
Omega-3 prostaglandins (PGs) and other essential metabolites such as protectins (complementary regulatory proteins that protect cell membranes; also called CD59 or MIRL) can be made only from EPA and DHA. A small amount of omega-3 PGs can result from ALA after the body converts it to EPA or DHA. ALA contributes only a little to the heart health benefits attributed to EPA and DHA since only about 1–5 % of ingested ALA becomes EPA and next to nothing DHA.

Passwater: Billy Shakespeare pointed out that a rose by any other name is still a rose and the famous quote, “a rose is a rose is a rose” was soon born. Dr. Dyerberg, is an omega-3 an omega-3 an omega-3 (suggesting that all omega-3s are equal) or are there major health differences between the omega-3 fatty acids?

Dyerberg: Consumers should be aware that just having “omega-3” on a product label doesn’t mean that it is necessarily heart healthy. The consumer should be interested in how much EPA and DHA are present. If the omega-3 is from ALA, then little of it will be converted into the form of omega-3 that produces heart benefits, which is EPA and DHA.

It can be concluded that to obtain desirable levels of plasma and tissue long-chained omega-3 fatty acids by supplementation, far lower and acceptable dietary doses are effective when supplementing with the preformed fatty acids such as fish oil-based supplements, than by giving the precursor ALA. To obtain desirable heart health benefits with ALA intake, this cannot be achieved by supplementation, but necessitates substantial dietary alterations.
The effect of ALA intake on cardiovascular risk markers is comparable to that of linoleic and oleic acid, and dietary changes reducing the intake of saturated fat and increasing the ALA intake are consequently advisable.

With regard to supplementation, ALA (often derived from flaxseed oil) has only minor effects on cardiovascular risk, probably due to the low conversion rate to long-chained omega-3 fatty acids.

Passwater: Is this conversion dependent on the rest of the diet?

Dyerberg: Yes, as an example, excessive omega-6 fatty acids such as the amount present in typical western diets can reduce the already meager amount of conversion of ALA to EPA.

Passwater: Please allow me to add some background information here. The conversion of ALA to long-chain EPA is influenced by diet as well as genetics. The high levels of linoleic acid (LA) in Western diets inhibit the low rate of ALA conversion further. If one consumes very high amounts of ALA and very little LA, the conversion of ALA to EPA can be enhanced, but it still falls short of what is required for optimal heart health. This is why the diet of the Eskimos was protective against heart disease and the diets in Western nations were not. This is the “why Eskimos don’t get heart attacks” story of Dr. Dyerberg’s research in Greenland is what we are discussing.

If one wishes to focus on preventing IHD, then one should focus on EPA and DHA. Our focus is on optimization and not merely deficiency. The state of knowledge and consensus of experts in the field is that ALA conversion to EPA is too inefficient to rely on for optimum heart health. Most scientists in the field agree and note the most recent studies confirm the lower range of conversion (more toward 1% than 5%) among those consuming standard western diets (4). A 2001 study using radioisotopes to follow the conversion found that “Only about 0.2% of the plasma ALA was destined for synthesis of EPA” (5).

Even if the conversion is many times higher in some, whatever the figure is, it isn’t enough to produce the heart benefits produced by EPA and DHA. One percent or 10% is not 100%. If ALA did produce sufficient conversion to EPA and DHA, there would have been no need for Dr. Dyerberg to go to Greenland and find EPA in the blood of the Eskimos. There would have been ample EPA in most peoples’ blood from ALA present in these diets and people would have only 10% of the IHD.

This is not to say that ALA is of little value or that it produces no benefit. It is an essential fatty acid and has multiple health benefits including benefits to overall cardiovascular health, as well as many benefits that we have yet to elucidate. Whole flaxseed also has merit because it supplies fiber and ALA. ALA is good and should be in everyone’s diet, but, ALA does not significantly contribute to the strong heart benefits of EPA and DHA which are due to the eicosanoids (derivatives of C20 fatty acids) that have been the focus of this discussion.

This point was the focus of a 2006 systematic review entitled, “Omega-3 Fatty Acids from Fish or Fish-Oil Supplements, but not Apha-Linolenic Acid, Benefit Cardiovascular Disease Outcomes in Primary- and Secondary-Prevention Studies,” which was published in the American Journal of Clinical Nutrition (6).

Earlier that year in the same journal, Dr. L. Arterburn and colleagues concluded, “A large proportion of dietary alpha-linolenic acid (ALA) is oxidized, and because of limited interconversion of n-3 fatty acids in humans, ALA supplementation does not result in appreciable accumulation of long-chain n-3 fatty acids in plasma” (7).

Not only do we inefficiently convert ALA to EPA, but adult humans do not make DHA from ALA. Adults cannot meet the needs of DHA for the developing fetus for neuro and brain development without dietary DHA. In infants, very high amounts of ALA did result in some increase in blood DHA in two studies (8, 9).

The International Society for the Study of Fatty Acids and Lipids (ISSFAL) published its official statement on ALA supplementation and conversion to long-chain polyunsaturated fatty acids in humans in 2009 in the peer-reviewed journal for experts in this field, Prostaglandins, Leukotrienes and Essential Fatty Acids (10). The ISSFAL is a body of over 500 lipid scientists. The meta analysis and review was conducted by Dr. J. Thomas Brenna of Cornell University, Dr. Norman Salem, Jr. of Martek Biosciences, Dr. Andrew J. Sinclair of Deukin University (Australia) and Dr. Stephen C. Cunnane of the University of Sherbrooke (Canada). The ISSFAL statement concludes, “With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA or other precursors.” The statements of the ISSFAL can be also viewed at

ALA supplementation can increase EPA slightly, but not optimally. However, the evidence clearly shows that precursor supplementation does not increase blood levels of DHA whether the supplement is ALA, EPA or stearidonic acid. The only known means to increase blood DHA by supplementation in adults is through the consumption of preformed DHA. Dietary DHA and blood/breast milk DHA has a remarkably tight dose-response relationship (11).

 A point of confusion in studies regarding fatty acids is whether the study involves supplementation or replacement. As Dr. Brenna points out, “In considering dietary interventions, seemingly conflicting results can be reconciled by attention to two concepts: supplementation versus replacement. Supplementation is the addition of a dietary nutrient with no other change in the diet. Replacement is the substitution of one food for another. In the case of ALA, supplementation is achieved by the addition of an oil rich in ALA, such as flax or perilla oil, to an otherwise unchanged diet. The major change in the diet is an increase in ALA, with insignificant changes in other fatty acids. Replacement would be achieved by substituting an ALA-rich cooking oil such as canola for ALA-poor oils such as corn, safflower, sunflower and peanut. Importantly, replacement also significantly alters the dietary proportion of the omega-6 PUFA, linoleic acid, a factor that is often overlooked in the interpretation of such studies. Linoleic acid competes with ALA for conversion to long-chain PUFAs and influences the answer” (12).

Two studies out of the 21 studies reviewed by the ISSFAL showed that conversion of ALA can be improved, but not to optimal EPA or DHA levels. In one study, DHA increased by an impressive 21%, when high-ALA perilla oil was used as cooking oil in place of moderate-ALA soy oil over 10 months. Perilla oil has about 15% linoleic acid, compared to more than 50% linoleic acid in soy oil, and thus linoleic acid was reduced to less than a third of pre-intervention levels (13). In the second study, the researcher instructed the participants to avoid foods high in linoleic acid, in addition to the supplementation with ALA (14). Good luck with that.

The U.S. Food and Drug Administration (FDA) has examined this question and announced on September 8, 2004 the availability of a qualified health claim for reduced risk of coronary heart disease (CHD) on conventional foods that contain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids (15). The qualified health claim does not apply to ALA.
Now, let’s resume our chat with Dr. Dyerberg. Dr. Dyerberg, are vegetarians usually sub-optimally nourished in terms of EPA and DHA even if they eat ample ALA, say from flaxseed sources? Are vegetarian diets overly rich in omega-6 fats as well?

Dyerberg: My answer is yes. It should, however, be stressed as I mentioned before, that if the diets are altered substantially, as the vegetarians’ and even more so the vegans’ are, the conversion of the 18 carbon PUFAs to their longer derivatives is enhanced. As the vegetarian diet generally is very rich in omega-6 fatty acids, I would recommend a supplementation with EPA and DHA.

Passwater: Would vegetarians be better off taking DHA derived from microorganisms or ALA?

Dyerberg: As mentioned, I would recommend that vegetarians—and especially vegans—add an EPA/DHA supplement to their diet. Whether this supplementation is based on fish oil or on algae is, in my opinion, of no importance. It is the fatty acids that work and your body does not differ between their origins.

Passwater: As our long-term readers realize, I often ask the same question in a couple of different ways as a means of emphasis and clarity just to be sure that everyone understands the issue. Let me repeat. So, in order to get the heart benefits, now so widely attributed to omega-3s, we need specific omega-3s—the long-chain EPA and DHA. Are EPA and DHA of equal value to the body? Can the body interconvert EPA and DHA?

Dyerberg: Both EPA and DHA have essential functions in the body. We do not know in detail all these metabolic processes. EPA and DHA can be inter-converted in the body to a certain extent, but especially the conversion of EPA to DHA is modest. Both fatty acids are present in marine food, and I see no reason to spend a lot of money in producing and supplementing with pure substances [i.e., standalone EPA and standalone DHA]. The human biology has developed with foods containing EPA and DHA (and AA!), and it is not a meaningful nutritional issue to search for the pure substances.

Passwater: At first, your research centered on PG formation from EPA and DHA. You linked the presence of EPA and DHA in the diet of Eskimos to a better balance of PG. Specifically, you found that EPA and DHA balanced the production of the PGs responsible for increased clotting time, blood platelet protection and vascular function to reduce blood platelet aggregation.

Now, research has moved to include membrane function and phospholipids. Your research has expanded into the role of EPA and DHA in forming better membrane phospholipids, which result in more fluid and thereby healthier membranes. The result is better health throughout the body in all systems. Thus, we can understand the better health that EPA and DHA produce beyond heart benefits. They affect every cell in the body via their important role in every cell membrane.

Evidence has emerged describing the biological essentiality of DHA for vision and the brain, its function and behavior. Most of the dry weight of the brain is lipid (fat) because brain activity depends greatly upon the functions provided by lipid membranes. [The brain is 60% fat, and DHA is the most abundant fatty acid in the brain, comprising 25–35%.] DHA is found in even greater concentrations—50–60%—in the retina.

Drs. Michael Crawford and Andrew Sinclair have shown that the brain needs DHA for its structure, growth and function. Drs. Gene Anderson and Nicholas Bazan have shown that vision requires docosahexaenoic acid (DHA). Dr. Claudio Galli has shown that DHA is important in learning.

We have discussed EPA and DHA in regards to eicosanoid balance. Is the association of DHA with brain health due to its relationship with membrane fluidity and neurotransmitters? Is this an oversimplification or is there scientific basis for such an association? Is EPA needed just as much as DHA for brain function?

Dyerberg: DHA has both structural and functional effects in the brain, and so have its derivatives, the protectins. But, EPA also seems to have essential roles related to brain function. A recent meta analysis of randomized, controlled trials actually finds that EPA, but not DHA, appears to be responsible for the efficacy of omega-3 long-chain PUFA supplementation in depressed individuals (16).

Passwater: On May 26, you were a featured speaker at the opening session of “A Celebration of DHA: Discovery, Achievement and Challenges for Global Health 40 Years On” at the Royal Academy of Medicine in London. A goal of the conference was to call for a new focus to be placed on brain disorders and ill mental health; they will be the top two burdens of ill health worldwide by 2020 and are the greatest threat to humankind today.

Do you see an important role for fish oils in reversing this trend?

Dyerberg: One of the most interesting nutritional findings in recent decades has been the effect of dietary factors on modifying age-related cognitive decline (dementia).

Several studies have found a negative association between intake of long-chained omega-3 fatty acids and the risk of dementia. In the Framingham Heart Study, the top quartile of plasma DHA levels was associated with a significant 47% reduction in the risk of developing dementia (17). I find these positive results in dementia, especially Alzheimer’s, one of the most promising fields of research in the huge area of omega-3 science.

Passwater: With attention being given to DHA for brain function, when did we realize that mothers’ milk contained DHA?

Dyerberg: In recent decades it has been realized that mothers’ milk contains both EPA and DHA, however in varied amounts dependent on the omega-3 intake of the mothers (18). The DHA/EPA ratio is generally from 2: 1 to 1: 1, but in Italy, mothers’ milk contained more EPA than DHA (0.17 and 0.12 wt% respectively) (19). Consequently, DHA and EPA as well as AA are essential for newborns as the content of mothers’ milk is considered the “gold standard” for the composition of food to the newborn.

Passwater: Forgive the redundant question, but I want to make this point clear. Does it matter what is the ratio of EPA to DHA in the diet? Does a higher ratio of DHA mean more goes to the brain? Are supplements having more DHA than EPA more suited for brain health and are supplements with more EPA than DHA better for heart health?

Dyerberg: Again, to me it is a nutritional issue. Marine food sources contain EPA as well as DHA in various amounts and in various relative amounts. As long as you get enough of both, either from food or from supplements, it is fine. This means 200–300 milligrams of each of these fatty acids per day.

Passwater: EPA and DHA are best known for their heart and brain benefits. However, a dazzling amount of research involving EPA and DHA is increasingly being associated with reduced inflammation, which has an impact on many conditions from arthritis to athletic recovery to heart health to cancer. Does this property of fish oil involve the PG-3 family of prostaglandins?

Dyerberg: A steady and increasing number of scientific publications have appeared, now reaching tens of thousands, broadening into areas of which we were not aware when the omega-3 arena was opened by us. This includes: the anti-inflammatory effects in rheumatic disorders, the possible effects in mood and psychiatric ailments and the positive influence on the development of the brain and nervous system in newborns. All the above results relate to the long-chained omega-3 fatty acids EPA and DHA.

Several studies have demonstrated that omega-3 fatty acid supplementation attenuates the inflammatory process in chronic inflammatory disorders (e.g., rheumatoid arthritis) (20). This effect has been used in the treatment of various autoimmune disorders and lends support to the notion of an anti-inflammatory effect of omega-3 fatty acids in IHD prevention. It also supports the explanation for the benefit of low doses of omega-3 fatty acids in coronary heart disease.

The anti-inflammatory effect of long-chained omega-3 fatty acids was first noticed when examining the chemo-tactic potency of leukotrienes generated from EPA compared to the leukotrienes formed from AA. Leukotrienes are proinflammatory agents synthesized in the white blood cells (leukocytes). Leukotrienes derived from AA exhibit 10- to 30-fold greater potency than the EPA-derived leukotrienes.

New families of locally acting anti-inflammatory substances generated from omega-3 fatty acids, termed resolvins, protectins and isoprostanes have recently been identified. These components control the duration and magnitude of inflammation. Given the potent actions of leukotrienes, lipoxins, adhesion molecules, resolvins and protectins in human disease, the intake of EPA and DHA may attenuate the development of atherosclerotic diseases.

Passwater: EPA and DHA affect the risk of heart disease in many ways ranging from the anti-clotting effect that you elucidated in the 1970s to rhythm-normalization of the heart beat to triglyceride level affects, and as we are now finding, also to anti-inflammation affects.

I like to look at the anti-inflammatory effect as just as important as any other risk factor in heart disease. Omega-6s produce the chemical messengers of inflammation. Chronically, this leads to silent inflammation and the smoldering fires in the arteries and heart that lead to many diseases. Omega-3s lead to the chemical messengers that produce the opposite effect. A balance of both is needed.

In addition to the omega-3 and omega-6 fatty acids we have been discussing, there are also omega-7 and omega-9 fatty acids. Omega-9 fatty acids are generally the monounsaturated fatty acids such as oleic acid common in the Mediterranean diet.

Omega-7 fatty acids generally seem to behave worse than saturated fatty acids. Omega-7 fats behave like saturated fats, not the monounsaturated fats that they are. Omega-7 fats raise LDL and lower HDL. There is no known role in the body for omega-7 fatty acids.
Are omega-9 fatty acids of value, and if so, what role do they play in the body?

Dyerberg: Omega-9 fatty acids such as oleic acid have good organoleptic qualities as constituents of olive oil. The omega-9 monounsaturated fatty acids do not share the cholesterol-increasing properties of saturated fats, and are therefore recommended to constitute 10% of our daily energy intake.

Passwater: Why COLD water fatty fish? Would fatty fish from the tropics also have EPA and DHA? Why are cold water fish usually cited for their EPA and DHA content? Is it because they need more body fat to survive the cold and thus have more stored EPA and DHA? Or is their diet different?

Dyerberg: The content of EPA and DHA is higher in cold water than in tropical marine fish. The reason may be that EPA and DHA have low melting points, thereby keeping the cells in the body of cold water fish in a flexible state in spite of the low sea temperature.

Passwater: Most fats in foods are in the form of triglycerides. Triglycerides are the most compact and calorie-dense compounds that can be converted into energy in the body.

During digestion, the fatty acids are stripped off the glycerol backbone of the triglycerides. They are reassembled later in the lymph and via the veins that reach the liver. They can then be burned for energy, used to make phospholipids and eicosanoids or converted back into TG for storage in fat cells.

Today, fish oil supplements are available in various forms. Regarding supplements, does it make much practical difference which form the fish oil is in (triglyceride, phospholipids, ethyl ester, free fatty acid or whatever)?
My preference is the basic triglyceride form that is produced merely by rendering. However, there are products that have been concentrated after further distillation and even available as highly purified ethyl esters. The latest research that I have seen suggests that all are about equally absorbed. The triglyceride forms enter the lymph and bloodstream earlier than the ethyl esters, but in the long-term, all are about equally absorbed, though at different rates at different periods of time. Again, I prefer the more natural distribution of EPA and DHA on the middle carbon of the glycerol backbone of the triglyceride, rather than the more randomize distribution of EPA and DHA on all three carbons that occurs during heavy distillation and the reformation during condensation of the distillate in the second position.

Is there any meaningful difference?

Dyerberg: Generally, the various fatty acid formulations (triglycerides, ethyl esters, free fatty acids, phospholipids) are well absorbed, especially when taken along with a meal. We found earlier that triglycerides compared to ethyl esters, are somewhat better absorbed. At the recent International Society for the Study of Fatty Acids and Lipids meeting in Maastricht, a study was presented finding exactly the same results.

Regarding the stereochemistry of the fatty acid position in the triglyceride molecule, several studies have documented that this has no effect on the bioavailability of the fatty acids.

Passwater: How much EPA/DHA do you recommend daily?

Dyerberg: The average intake of marine omega-3 fatty acids in Americans is low (approximately 200 mg/day), and for many it is zero! It is far below what today is considered a target intake in the United States, namely, 400–500 mg/d of EPA + DHA. For pregnant females, we recommend a daily intake of 200–300 mg of DHA, due to the special need of DHA for the fetus’ brain development.

Passwater: Thank you, Dr. Dyerberg. Let’s pause once again and resume our chat with a look at some of the research with fish oil that documents the health benefits with which we began this conversation. WF

1. H.M. Evans and G.O. Burr, “Increased Efficacy of Subcutaneous when Compared with Intraperitoneal Administration of the Ovarian Hormone,” Am. J. Physiol. 77 (3), 518–210 (1926); H.M. Evans and G.O. Burr, “A New Dietary Deficiency with Highly Purified Diets,” Proc. Soc. Exp. Biol. Med., 24, 740–740 (1927).
2. G.O. Burr and M.M. Burr, “A New Deficiency Disease Produced by the Rigid Exclusion of Fat from the Diet,” J. Biol. Chem. 82 (2), 345–367 (1929).
3. Food and Nutrition Board, Institute of Medicine of the National Academies, Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (The National Academies Press, Washington, D.C., 2002).
4. Fats of Life Newsletter, ”Fat Basics”, accessed June 24, 2010.
5. R.J. Pawlosky, et al., “Physiological Compartmental Analysis of Alpha-Linolenic Acid Metabolism in Adult Humans,” J. Lipid Res. 42 (8), 1257–1265 (2001).
6. C. Wang, et al., “n-3 Fatty acids from Fish or Fish-Oil Supplements, but not Alpha-Linolenic Acid, Benefit Cardiovascular Disease Outcomes in Primary- and Secondary-Prevention Studies: A Systematic Review,” Am. J. Clin. Nutr. 84 (1), 5–17 (2006).
7. L.M. Arterburn, et al., “Distribution, Interconversion, and Dose Response of n-3 fatty Acids in Humans,” Am. J. Clin. Nutr. 83 (6 Suppl), 1467S–1476S (2006).
8. K.J. Clark, et al., “Determination of the Optimal Ratio of Linoleic Acid to Alpha-Linolenic Acid in Infant Formulas,” J. Pediatr. 120 (4 Pt 2), S151–S158 (1992).
9. C.L. Jensen, et al., “Biochemical Effects of Dietary Linoleic/Alpha-Linolenic Acid Ratio in Term Infants,” Lipids 31 (1), 107–113 (1996).
10. J.T. Brenna, et al., “Alpha-Linolenic Acid Supplementation and Conversion to n-3 Long-Chain Polyunsaturated


Dr. Richard Passwater is the author of more than 40 books and 500 articles on nutrition. He is the
vice president of research and development for Solgar Vitamin and Herb. Dr. Passwater has been WholeFoods Magazine’s science editor and author of this column since 1984. More information is available on his Web site,

Published in WholeFoods Magazine, Aug. 2010 (epub July 20, 2010)