What Are the Real Differences Between EPA and DHA?

Where do you want your EPA and DHA to go? Know the signs.

When you read anything about fish oil, the acronyms EPA and DHA always go together. But what do they really mean, and what’s the difference between them? The reality is that the two key omega-3 fatty acids (EPA and DHA found in fish oil) do a lot of different things, and as a result the benefits of EPA and DHA are often very different. That’s why you need them both. But as to why, let me go into more detail.

Benefits of EPA

The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA is the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons.

  • EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA.
  • The more EPA you have in the diet, the less AA you produce.

This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.)

DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane, you can’t make inflammatory eicosanoids.

Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme, just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.

The various enzymes (COX and LOX) that make inflammatory eicosanoids able to accommodate both AA and EPA, but again due to the greater spatial size of DHA, these enzymes will have difficulty-converting DHA into eicosanoids. This makes DHA a poor substrate for these key inflammatory enzymes. Thus DHA again has little effect on cellular inflammation, whereas EPA can have a powerful impact.

Finally, it is often assumed since there are not high levels of EPA in the brain, that it is not important for neurological function. Actually, it is key for reducing neuro-inflammation by competing against AA for access to the same enzymes needed to produce inflammatory eicosanoids. However, once EPA enters into the brain, it is rapidly oxidized.This is not the case with DHA.

The only way to control cellular inflammation in the brain is to maintain high levels of EPA in the blood. This is why all the work on depression, ADHD, brain trauma, etc., has demonstrated that EPA is superior to DHA.

Benefits of DHA

At this point, you might think that DHA is useless. Just the opposite, because DHA can do a lot of different things than EPA and some of them are even better.

First is in the area of omega-6 fatty acid metabolism. Whereas EPA is the inhibitor of the enzyme (D5D) that directly produces AA, DHA is an inhibitor of another key enzyme, delta-6-desaturase (D6D), that produces the first metabolite from linoleic acid known as gamma linolenic acid or GLA.

However, this is not exactly an advantage. Even though reduction of GLA will eventually decrease AA production, it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA, it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to make anti-inflammatory eicosanoids.

In my opinion, the key benefit of DHA lies in its unique spatial characteristics. As mentioned earlier, the extra double bonds and length of DHA compared to EPA means it takes up a lot more space in the membrane. Although this increase in spatial volume makes DHA a poor substrate for phospholipase A2 as well as the COX and LOX enzymes, it does a great job of making membranes (especially those in the brain) a lot more fluid as the DHA sweeps out a much greater volume in the membrane than EPA.

This increase in membrane fluidity is critical for synaptic vesicles and the retina of the eye because it allows receptors to rotate more effectively, thus increasing the transmission of signals from the surface of the membrane to the interior of the nerve cells. This is why DHA is a critical component of these parts of the nerves. On the other hand, the myelin membrane is essentially an insulator so that relatively little DHA is found in that part of the membrane.

This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes. Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes. In addition, these greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA.

As a result DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery, thus reducing the likelihood of developing atherosclerotic lesions. Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.

Common Effects for Both EPA and DHA

Not surprisingly, there are some areas in which both EPA and DHA appear to be equally beneficial. For example, both are equally effective in reducing triglyceride levels. This is probably due to the relatively equivalent activation of the gene transcription factor (PPAR alpha) that causes the enhanced synthesis of the enzymes that oxidize fats in lipoprotein particles.

There is also apparently equal activation of the anti-inflammatory gene transcription factor PPAR-gamma. Both seem to be equally effective in making powerful anti-inflammatory eicosanoids known as resolvins. Finally, although both have no effect on total cholesterol levels, DHA can increase the size of LDL particle to a greater extent than EPA can.

So Now What?

EPA and DHA do different things, so you need them both.

If your goal is reducing cellular inflammation, then you probably need more EPA than DHA. How much more? The most effective way to find out how much fish oil you need is to test your blood. Our Cellular Inflammation Test Kit allows you to test your personal levels at home. You will receive a detailed report with your AA and EPA levels, as well as your Cellular Inflammation Score, and personalized wellness recommendations. Then, you will never need to guess how much fish oil you should take.

Already know how much fish oil to take? Dr. Sears’ OmegaRx Fish Oil is the best way to get high levels of both EPA and DHA.

Find out your Cellular Inflammation Score
Take the easy finger-stick Cellular Inflammation Test today.

Zone Labs AA/EPA Ratio Blood Test KitEverything inside the Zone Cellular Inflammation Test Kit.

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About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 45 years to the study of lipids. He has published 40 scientific articles and holds 14 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 14 books, including the New York Times #1 best-seller, The Zone, which have sold more than 6 million copies in the U.S. and have been translated into 22 different languages.


  1. Marsha Scheitlin

    I have a son with Down Syndrome which is simiiarities to Alzheimer’s Disease and we are using SPM Active by Metagenics which I’m hoping will help with the conversion of EPA/DHA to the next step. In the light of this, how would this affect your recommendation for EPA/DHA or would we just have to test? Resolvin E1 has been or is currently being investigated in Down Syndrome mouse models and shows promise but I don’t think that the research has been published yet. You say that EPA oxidizes in the brain, why is that and would the SPM Active product prevent that? Very interesting in any effects on genes or insulin.

  2. Grant Richardson

    I have the same question as Nocholas Potter about whether the body really does convert DHA to EPA as needed, for the same reason he asked.

    Your answer “the progression of EPA into DHA is far more robust than the retroconversion of DHA to EPA” seems to contradict a claim I read in another article:
    ” [w]hile some moderate net rise in the level of EPA (eicosapentaenoic acid) was found with higher levels of ALA in conjunction with omega-6:omega-3 ratios lowered to 3:1; no net rise in the level of circulating DHA was found across the various fatty acid mixtures and ratios (…) For example, the feeding of 10.7 grams (10,700 mg) of ALA from flaxseed oil over a four week period failed to provide any significant net rise in the low levels of DHA present in the breast milk of lactating women.”

    Could you help me out on this?

    • Barry Sears

      The particular example you referred to is dealing with the conversion of ALA into DHA, not in the blood, but in breast milk. The regulation of fatty acid content of breast milk is more tightly controlled than the levels of EPA and DHA in the blood. The rate of conversion of ALA into EPA in the blood is very slow and conversion of EPA into DHA is also slow in short-term supplementation studies. However, as shown in a global survey (Stark et al. Prog Lipid Res. 2016 Jul;63:132-52), DHA levels are always higher than EPA. Thus if the steady state levels of of EPA are at 4%, then the steady state levels of DHA will always be greater than 4%. I usually recommend taking the AA/EPA ratio test once a year to sample steady state levels of both fatty acids which provides a good estimate of the balance of initiation to resolution of inflammation in the body.


    Is it true that consuming more DHA than EPA (with a ratio of 2:1) will help for the brain function such as clarity & fluidity?


    • Barry Sears

      The data is clear that EPA has a far stronger effect in treating mood disorders than does DHA. That’s why I feel a 2:1 EPA to DHA ratio appears to be the best for virtually all conditions requiring greater resolution of inflammation.

  4. Tim Rosato

    I would like to ensure I am getting enough DHA and EPA. I follow a vegan diet and try to limit too much Omega 6. I don’t want to take fish oil. If I consume 5 grams of ALA a day (e.g., via flaxseeds, chia seeds) shouldn’t my body be able to convert enough to adequately meet my dietary needs of EPA and DHA? If not, what can I eat or take by way of supplement to boost EPA/DHA? I have ADHD and would like healthy dose of EPA/DHA to help with ADHD symptoms.

    • Barry Sears

      There are vegetarian sources from algal that contain both EPA and DHA. These would be excellent sources for you.

  5. Nicholas Potter

    @drsears I have recently heard a verbal claim that if there are adequate levels of DHA that there will be adequate levels of EPA but the inverse is not true. I researched in #OMEGARXZONE and saw the synthesis flow diagram on page 246 and think I understand the pathway. However, I can’t seem to find a specific citation or other information to determine if the claim is valid. The person who made the claim has interest in the sale of an algae based DHA product.
    Thank you

    • Barry Sears

      The retroconversion of DHA to EPA is only 10% make it a very inefficient process. The progression of EPA into DHA is far more robust. This is why you will always have more DHA than EPA. I try to make that you have at least 4% EPA in the blood to ensure an equal, if not greater, amount of DHA.

  6. Larry Hartman

    great article for scientists, as much as I tried I did not understand one bit of it. Definitely not for the everyday Joe

    • Barry Sears

      Bottom line, you need both EPA and DHA because they do different things. However, you need therapeutic levels of both. Since EPA is converted into DHA, as long as you have at least 4% EPA in the blood, you will have an equal, if not greater, amount of DHA at the same time.

  7. Dee Dee Mares

    Does Emu Oil contain EPA or DHA Omega 3 fatty acids, or is it’s anti-inflammatory properties based on other factors?

    • Barry Sears

      Emu doesn’t contain any EPA or DHA, but I suspect that it may contain various pro-resolving meditators at very low concentrations to explain many of its remarkable anti-inflammatory benefits.


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