How Omega-3 Fatty Acids Improve Health

Can of sardines

Omega-3 fatty acids, types of polyunsaturated fatty acids that are most abundant in fish and fish oil, have long been associated with lower risk and/or mortality from heart disease. Meta-analyses of supplementation trials have, however, been equivocal as to their benefit. In this article we’ll see whether it can be ascertained whether they have benefit or not, and whether and how omega-3 fatty acids improve health.

Epidemiological evidence

The modern theory that fish consumption, along with its abundant provision of omega-3 fatty acids, prevents heart disease comes from studies of Greenland Eskimos, who have a very low rate of heart disease and a very high consumption of fish and other marine animals. Below is a chart that shows tissue content of omega-3 and its relation with cardiovascular (CVD) mortality – coronary heart disease and stroke mainly. (Chart source.) The tissue compositions were calculated, not directly measured.

It can be seen that the relation between omega-3 tissue levels and cardiovascular mortality holds across many countries as well as within countries. Even in Japan, a country with generally high fish intake and low heart disease risk, increasing consumption of fish and omega-3 was associated with substantially reduced risk of heart disease, mainly non-fatal.

One wonders, however, what other factors could be at play. In Greenland, for example, at least at the time studied, one would expect that the inhabitants had a low intake of processed foods that contained sugar, refined flour, and vegetable (seed) oils.

Trials of fish oil supplementation

Since these results were found, many trials have been done in which subjects were supplemented with fish oil and followed for heart disease and other clinical endpoints. Results have been mixed.

The GISSI-Prevenzione trial, carried out in Italy, gave one gram of omega-3 daily to people who had suffered a recent heart attack, and found an up to 20% decreased risk of death in those who took it, compared to no supplementation.

The Lyon Diet Heart Study used a “Mediterranean diet” as the intervention, part of which included the use of a margarine enriched in alpha linolenic acid, an omega-3 fatty acid. The subjects had also suffered a heart attack before placed on the intervention.  Subjects in that trial had a 50 to 70% lower risk of recurrent heart disease.

Meta-analyses have been mixed, however.

One meta-analysis found that supplementation with omega-3 fatty acids “reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease”, with decreases of from 20 to 30%.

Another, more recent meta-analysis found no effect. Another found no effect in secondary prevention of heart disease.

What could be going on to give such mixed results?

One possibility is that supplementation doesn’t increase the omega-3 index equally in all patients or all trials, due to issues of bioavailability and trial design. Since tissue composition of omega-3 is thought to be behind a decrease in CVD, just giving it to someone doesn’t guarantee a rise in the omega-3 index, which is a measure of omega-3 in red blood cells.

When actual blood levels of omega-3 fatty acids are measured in male physicians, large reductions in cardiac sudden death were found, as much as 90% reduction, even adjusted for confounding factors..

Another possibility, related to the first, is a high background intake of omega-6 fatty acids, which are abundant in seed oils, and which are consumed massively in most of the developed world. Far greater intake of omega-3 is necessary in someone with a high intake of omega-6 to raise tissue levels to one that reduces risk. It’s estimated that in the U.S., a “healthy dietary allowance” of DHA and EPA, the two main omega-3 fatty acids found in fish oil, could be reduced ten-fold if omega-6 consumption were greatly reduced also. The reason is that omega-6 and omega-3 fatty acids compete with each other for incorporation into body tissues, so the less there is of one, the less is needed of the other.

In all large interventional trials, no consideration was given to baseline omega-3 fatty acid levels. (See here.) In those with high initial levels, little to no effect of supplementation would be seen. Most were told to take capsules at breakfast, which for many is a low-fat meal, hindering absorption. This is similar to some studies on iron depletion, where initial and final ferritin levels are important, not the mere fact of phlebotomy. In omega-3 trials, the initial and final tissue levels are important, not the mere fact of supplementation. The intervention must actually do what it is designed to do.

In drug trials, only the intervention group gets the drug, but in trials of omega-3, both groups have a certain level of them in their tissues. Participants are recruited without considering baseline omega-3, and therefore there will be a substantial overlap in omega-3 tissue levels between the intervention and the control groups. In this way, randomized controlled trials are flawed when used in nutrition.

Check out the following chart. (Source.) It shows that post-intervention, after the intervention group got fish oil and the control group did not, there’s a huge overlap in red blood cell omega-3 fatty acids between the two groups. In fact, the upper half of the control group and the lower half of the intervention group could practically be interchanged. An observation group excluded from the trial because they either ate fish regularly or already took fish oil had nearly identical levels of erythrocyte omega-3 as the intervention group.

This paper also points out that by the year 2000, the fish oil genie was out of the bottle, as reports were appearing in the mainstream press about the benefits of fish oil, and many people started taking it. As it happens, trials conducted in the 1980s and 1990s had much better results than trials conducted after 2000, likely because the earlier trials were able to create a large difference in tissue omega-3 concentrations between intervention and control groups. After 2000, many more people ate fish or took fish oil, and differences between intervention and control groups may have been far less.

Composite end points in the trials may be another factor. For example, if the main effect of omega-3 is to lower the risk of sudden cardiac death, but the trial uses a composite end point of sudden cardiac death, myocardial infarction, and stroke, the difference between intervention and control groups decreases.

Statin use may be another confounding factor. A recent study found that statin use may mitigate the beneficial effects of omega-3 fatty acids. Since so many patients at risk for CVD take statins now, that could account for differing results in trials, depending on how many people in the trial were taking them, and how much statin use varied between intervention and control groups.

Yet another possibility is that the associations between fish consumption and less heart disease are real, but that something else in the fish wholly or partially causes less heart disease. Maybe protein, for example, or the particular amino acid composition of fish protein, or that fish displaces food that causes heart disease.

Making sense of it all

As we’ve seen, epidemiological evidence strongly supports both fish consumption and levels of tissue omega-3 as preventative of cardiovascular disease, but randomized trials have been equivocal.

In my view, the fact that tissue levels of omega-3 strongly support the preventative effect, then omega-3 fatty acids do indeed prevent CVD, possibly even in spectacular fashion.

But, a high background intake of omega-6 fatty acids from seed oils can negate the benefits of omega-3 consumption. If someone consumed a lot of processed food that was high in seed oils, or consumed them in some other fashion, they may get zero benefit from omega-3 supplementation.

With a low background level of omega-6 consumption, safe levels of omega-3 can be attained with only a tenth the amount of omega-3 as compared to with a relatively high background of omega-6.

Therefore, the best policy, as I’ve noted before, would appear to be to lower vegetable (seed) oil consumption as much as possible. That’s possibly even more important than supplementing with fish oil.  The key is to bring them into balance. If you consumed no added sources of omega-6, then consuming fish a couple of times a week may be enough.

I do take fish oil, but not daily, a teaspoon of cod liver oil a couple to three times a week. Each teaspoon provides about 1 gram of omega-3 fatty acids. I also strive to consume zero vegetable oils; I also minimize consumption of high omega-6 nuts, and chicken, which contains a relatively high amount.

PS: Check out my Supplements Buying Guide for Men.

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  1. Mellie Walks says:

    I definitely agree with lowering omega 6’s by cutting out vegetable oil, nuts and chicken. I also avoid pork too!

    • P. D. Mangan says:

      Avoiding pork? Beyond the pale!

    • Nils says:

      Why nuts? They’re positively associated with decreased CVD and overall mortality. There’s probably an important difference between processed Omega 6 oils and raw whole nuts.

  2. Herman Rutner says:

    Herewith a dissenting comment. The chart shows calculated not experimental tissue, data, possibly erroneously making the Quebec Inuit diet similar to the far healthier balanced Japanese diet. The Eskimo diet also included significant consumption of berries, carbs and veggies in summer time further reducing the damage from the 100% blubber diet of 3100 cal per day in winter time..
    Pasted below is an excerpt of an epidemiological review article dated 1987 cited in a 2015 newsletter of Dr Mc Dougall, a high carb diet proponent:
    “Eskimos Suffer from Atherosclerosis
    Claims that Eskimos were free of heart (artery) disease are untrue. A thorough review of the evidence concludes that “Eskimos have a similar prevalence of CAD (coronary artery disease) as non-Eskimo populations, they have excessive mortality due to cerebrovascular strokes, their overall mortality is twice as high as that of non-Eskimo populations, and their life expectancy is approximately 10 years shorter than the Danish population..
    Mummified remains of Eskimos dating back 2,000 years have shown extensive hardening of the arteries throughout their brains, hearts and limbs; as a direct consequence of following a carnivorous diet of birds, caribou, seals, walrus, polar bears, whales, and fish. The June 1987 issue of National Geographic magazine carried an article about two Eskimo women, one in her twenties and the other in her forties, frozen for five centuries in a tomb of ice. When discovered and medically examined they both showed signs of severe osteoporosis and also suffered extensive atherosclerosis, probably the result of a heavy diet of whale and seal blubber.”
    I take a teaspoon of molecularly distilled codliver oil daily along with 400 U of mixed tocopherols as an in vivo preservative.

    • Drifter says:

      Assuming what you say is correct, I don’t think this is strong evidence of an issue with the fat in their diet, however it may be an issue of lack of nutrients (vitamin C?). As Chris Masterjohn has written about, many of the inuit were severely hypothyroid, which they understood and counter-acted by eating the thyroid glands animals they killed in order to become fertile. Hypothyroid is in itself a major CVD risk factor, likely causual. Also, egyptian mummies who apparently ate a diet low in fat and very much like what mainstream medicine currently recommends had severe CVD and cancer, so this sounds like yet another case of confirmation bias on part of McDougal & Co. If the blubber were such a problem, low carb, high fat diets would have uniformly bad results instead of the widely documented good results that many people experience, including plaque regression.

  3. Drifter says:

    I think there’s another related issue that gets no attention as far as I know but seems to be of huge importance. Dr. Gundry brought up a point in one of his podcasts that women who eat very low fat diets and have children in close succession will often have a mentally healthy first child, but the later children will have developmental difficulties. I have seen this exact thing in several cases within my social circle. He attributes this to the woman’s body having enough of the type of fat stored up to build the baby’s brain for the first child, but not having sufficient fat for the later children and if I remember correctly he specifically attributed it to a lack of either DHA or EPA which is very highly concentrated in the brain and which the mother has to have enough of to produce a mentally healthy baby. This would seem to be especially an issue for vegan women.

    • TeeDee says:

      Drifter, thanks so much for your input, here. With so many instances of people saying the exact opposite of one another with regards to nutrition, it comes down to who can provide the most sound, established evidence.

  4. Bill says:

    I am glad that you have written this PD. I had my GP tell me last Friday that fish oil is not thought now to be healthy for folks with heart issues. I did not for a second believe him. But here you have replied to that BS.

    And this is the bloke who is still banging on about taking statins… I have been seeing this GP for 17 years. But I am now looking around for someone who is better informed and not a statinologist…

  5. oil boy says:

    What about exotic oils like avocado or walnut? Are these evil seed oils too? Are we limited to tallow, lard, coconut oil, and butter?

  6. Nick says:

    I’ve doctored up a graphic I’ve seen in the Twittersphere (with permission of the author) listing o3 & o6 values of various foodstuffs: .

    Didn’t I read somewhere (Mark’s Daily Apple?) that nuts aren’t as treacherous, because of the fiber and whatever else in them?

    • P. D. Mangan says:

      Yes, I saw that, great graphic.Omega-6/3 levels in food.

      As for nuts, I avoid them precisely for the reason seen in this graphic, high omega-6. For many, probably most, people, nuts are better than what they normally eat, but if someone eats well, nuts are a net detriment in my opinion.

      • Bill says:

        PD, nice tip about walnuts. I will have to ease back on them.

        But with canned fish surely the type of oil also added in the can, makes a difference. I’ve been checking what oils are in the canned sardines, salmon and tuna on the shelf before buying. It’s almost all blended oil or sunflower here. And the tuna in virgin olive oil has recently disappeared off the shelf no longer stocked.

        So now I;m buying tuna etc in brina

        • P. D. Mangan says:

          Hi Bill – definitely makes a difference. If you buy fish packed in garbage oil, it turns the food from healthy to detrimental.

  7. Rick says:

    I limit all PUFA including fish oils. They turn rancid in a warm high oxygen environment like the human body and suppress thyroid function. Humans should consume cream, butter, coconut oil and other saturated fats. Olive oil is neutral, not as good as saturated and not bad as polyunsaturated.

  8. Brad Lemley says:

    This is a tough one. Ray Peat, who has a pretty sophisticated understanding of nutrient-hormone interaction, objects to fish oils for the same reasons that Rick cites. He says if you eat fish, eat warm-water types, as their fat is more saturated. My take is that cold water fatty fish is okay on occasion, but the popular conception that fish is the only safe form of animal flesh is overdoing it, and supplemental fish oil should be taken sparingly if at all.

  9. Hey D.

    I just finished the Ultimate Omega-3 diet by Evelyn Tribole. It goes over a lot of this. She is sorta anti-red meat as well so folks certainly can’t accuse her of “paleo bias”.

    Decent, quick read.

  10. Shameer Mulji says:

    What are your thoughts on this studying showing increased lipid peroxiation / oxidative stress via a combination of heme iron (red meat) + fish oil intake?

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