Omega-3s: Everything You Need to Know

May 19, 2020

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omega-3s As a health-minded individual, you’ve no doubt gotten the memo that omega-3 fatty acids are important. You may dutifully eat your weekly servings of small, oily fish. Perhaps a fish oil pill is even part of your daily supplement routine. But do you know why?

Looking back, I used to write about omega-3s a lot in the early days of Mark’s Daily Apple (more than a decade ago, geez!) Since then, I’ve covered the topic here and there, but I thought it was time for a refresher. Today I’m going to focus on giving you a broad overview of their function and an update on the state of the research literature.

It would be impossible to cover all the reasons that omega-3s are important for health in a single post, nor all the areas of ongoing research. I’ll try to hit the big ones here. Let me know in the comments what else you’d like me to cover in future posts.

What Are Omega-3 Fatty Acids?

Omega-3s are essential polyunsaturated fatty acids (PUFAs)—“essential” means the body can’t synthesize them. We have to get them from food or supplements.

As Primal folks, you might have an adverse reaction to the word “polyunsaturated.” It’s true that in the ancestral health world, we tend to be wary of PUFAs—or really, oils containing high proportions of PUFAs such as safflower and canola—due to their propensity to become rancid and be pro-inflammatory. However, this is a don’t-throw-the-baby-out-with-the bathwater situation. First, when it comes to overconsumption and inflammation, we are primarily concerned with omega-6 fatty acids, not omega-3s. Second, PUFAs, both omega-3s and even the oft-maligned omega-6s, serve many functions in the human body.

I’ll return to the issue of omega-6s vis-à-vis omega-3s later in this post. For now, I just want you to understand that omega-3s are polyunsaturated, essential, and important.

A Quick Primer on Polyunsaturated Fatty Acids

Omega-3s and omega-6s are both types of polyunsaturated fatty acids. What does this mean? Fatty acids comprise chains of carbon atoms of differing lengths. Picture each carbon atom having four arms. They “hold hands” to form the chain. With the remaining hand(s), they hold on to one or more hydrogen atoms.

If each carbon atom uses one hand to hold the carbon on its left and one to hold the carbon on its right, that leaves two hands free for hydrogen. When each carbon is attached to two hydrogen atoms, these fatty acids are called saturated.

Sometimes carbons form double bonds, meaning they use two hands two grab a neighboring carbon. This leaves only one hand free for hydrogen. These are unsaturated fatty acids. When fatty acids only have one double bond along the carbon chain, they are called monounsaturated. When they have multiple double bonds, they are polyunsaturated.

The number in the name of the fatty acid tells you where you can find the first double bond. In omega-3s, the first double bond is on the third carbon atom from the omega (methyl) end. In omega-6s, it’s on the sixth carbon atom.

Double bonds form “kinks” in the fatty acid chains, affecting the shape, and ultimately the function, of the fatty acid. It is not inherently bad for a fatty acid to be polyunsaturated, but it does mean that they are especially vulnerable to oxidation. Omega-3 and omega-6 fatty acids (along with their less appreciated cousins, the omega-9 fatty acids) are each important in their own way.

The Three Main Types of Omega-3s

There are many forms of omega-3 fatty acids, of which three are particularly noteworthy for humans:

Alpha-linolenic acid (ALA)
Eicosapentaenoic acid (EPA)
Docosahexaenoic acid (DHA)

ALA is the most abundant in the diet. In humans, its main biological function is as a precursor for EPA and DHA. ALA that is not converted to EPA or DHA is used mainly for energy.

Even though ALA is converted into EPA and DHA, the latter two are still considered essential (or “conditionally essential”) because conversion rates are too low to provide all the EPA and DHA needed for optimal functioning. Females are better able to convert ALA thanks to higher estrogen, but both sexes need to get EPA and DHA in their diet and/or from supplements.¹

But What Do Omega-3 Fatty Acids DO?

Omega-3s are found throughout the body, notably in cell membranes, where they affect the fluidity of the membranes and, ultimately, gene expression. All the omega-3s play numerous important roles in the body, including in cellular metabolism, immune system function, and cardiovascular health.

EPA is involved in producing signaling molecules called eicosanoids that modulate inflammation, while DHA is an important structural component especially in the nervous system and retinas. Both EPA and DHA are generally considered to be anti-inflammatory, although that’s something of an oversimplification. Their effect on the immune system depends on the context.

Generally speaking, though, EPA and DHA exert anti-inflammatory effects, in contrast to omega-6s, especially arachidonic acid (AA), which tend to be pro-inflammatory. Omega-3s work their anti-inflammatory magic in a number of ways, including by producing specific eicosanoids, suppressing pro-inflammatory transcription factors, decreasing production of inflammatory cytokines, and by “turning off” inflammatory responses once they have done their job.² ³

Omega-3s’ Roles in Disease

Because inflammation is characteristic of so many disease states, omega-3s are a major area of research interest. Researchers have studied how omega-3s interact with practically every major disease and developmental process you can think of.

I’ll tell you up front, we still have a lot more questions than answers. Sometimes it seems that omega-3 intake in the diet buffers against a certain health issue, but the results aren’t replicated in randomized control trials. (It may be that the initial epidemiological studies are flawed – I’m highly skeptical of this methodology overall.) Experiments often yield inconsistent results. There may be differences between getting omega-3s from whole foods versus supplements, or certain populations may respond differently than others to supplementation. Studies may not be targeting the optimal dose. On and on.

The fast is, there are few “knowns” with regard to specific diseases. It’s fair to say that it’s clearer that omega-3s are important in a global sense — for overall health — than for any specific disease or disorder.

Cardiovascular Health

The potential for omega-3s to prevent or treat cardiovascular disease has probably has received the most attention. There is lots of data here… and the results are all over the map. Let me try to summarize some of the major findings, focusing on recent meta-analyses where possible:

Observational studies suggest that people who eat one or two servings of fish per week have better cardiovascular health than people who do not.⁴
A recent meta-analysis evaluated 19 studies, with 45,637 participants, in which researchers assessed biomarkers of omega-3s—basically, how much omega-3 people had in their systems. ALA and DHA were associated with lower risk of fatal coronary heart disease but not total coronary heart disease.⁵
Some research suggests that omega-3 supplementation may be particularly helpful for individuals with existing cardiac disease, at least in terms of reducing the risk of cardiac and all-cause mortality.⁶ However, other analyses show minimal benefit.⁷ ⁸
EPA and DHA may be useful in reducing high blood pressure.⁹

Overall, the data from many studies seems promising, though it gets messy when you really dig into the literature. Despite the messiness, last year the U.S. Food and Drug Administration concluded that there is “credible evidence” that EPA and DHA may reduce the risk of coronary heart disease and hypertension.¹⁰

On the other hand, a Cochrane Review published earlier this year takes a different stance.¹¹ The authors conclude that there it is unlikely that omega-3 supplementation meaningful affects mortality, although they concede that there might be some benefit for cardiovascular disease events and arrhythmia. Effects of supplementation may vary by dose, which might help explain inconsistencies between studies.¹² ¹³ Optimal dose could depend on what outcomes you’re hoping to achieve.

One area where omega-3 supplementation seems to shine is in the treatment of hypertriglyceridemia, or high triglycerides.¹⁴ Multiple studies show a benefit, but at doses higher that you’re likely to take over the counter. To reduce triglycerides, the American Heart Association recommends taking 2 to 4 grams of EPA+DHA under a doctor’s supervision.¹⁵

Mental Health

Omega-3s are abundant in the brain and play key roles in neuronal functioning. It’s no surprise that they would be considered in the treatment of mental health disorders. Some disorders, notably depression, are also thought to be inflammatory, making anti-inflammatory omega-3s a potentially useful intervention. What does the data say?

People who eat more fish are at lower risk of depression¹⁶, and individuals diagnosed with depression may have chronically low levels of omega-3s in their cells.¹⁷ ¹⁸
Some studies show that omega-3s, especially EPA, reduce depressive episodes¹⁹ and clinical anxiety²⁰.
Omega-3s are also under investigation for a number of other mental health disorders including schizophrenia and bipolar disorder, but there is not enough evidence to draw firm conclusions about their efficacy.²¹

Aging and Age-Related Cognitive Decline

There are multiple pathways by which omega-3s might support healthy aging, especially in the brain. A couple small studies demonstrated positive effects of supplementation on brain structure and function in older adults.²² ²³ However, results have been inconsistent overall, with no clear benefit for preventing or treating Alzheimer’s or dementia.

Other studies have looked at whether omega-3s can improve physical functioning. One found that in older adults with coronary artery disease, EPA+DHA improved functioning and was associated with getting more weekly exercise.²⁴ Another showed increased muscle protein synthesis with supplementation.²⁵

Rheumatoid Arthritis (RA)

Likely due to their anti-inflammatory properties, omega-3s show promise for the treatment of rheumatoid arthritis. A recent meta-analysis of 20 randomized control trials linked omega-3 supplementation to improvements in 8 distinct health markers for RA, including stiffness in the morning and joint tenderness.²⁶ Some studies, but not all, find that omega-3 supplementation reduces arthritis pain.²⁷

Cancer

The data with regard to cancer are too disparate to summarize neatly. Researchers are particularly interested in the possibility that omega-3s may reduce incidence of breast and colorectal cancers. I’ll be keeping my eye on this.

One important note is that some studies have found limited evidence of a positive association between omega-3 intake and prostate cancer. However, other large-scale epidemiological studies suggest that men who consume more fish are at lower risk for prostate cancer.²⁸ ²⁹ It’s not clear what’s going on here, but it does suggest that you should talk to your doctor if you’re considering supplementing with omega-3s and you have had, or are at high risk for developing, prostate cancer.

What does it all mean?

Here’s how I read the situation: There is no doubt that omega-3s are crucial for health. You don’t want to be chronically low in omega-3s. Whether there is a benefit for supplementing with omega-3s—especially above and beyond what you get from your diet—depends on what you hope to get out of it. If you’re thinking about using omega-3s to treat a specific health issue, talk to your doctor. There are too many variables at play—your dietary intake and health status, types and omega-3s and dosing—to make blanket recommendations.

How to Get Omega-3s

Dietary Sources of Omega-3 Fatty Acids

Marine animals are the primary dietary sources of EPA and DHA in the human diet. This is why I and others have argued previously that fish and shellfish played a critical role in human evolution.³⁰ The abundance of DHA in particular was probably pivotal to our advanced brain development.

Some of the best sources of EPA and DHA are salmon, mackerel, anchovies, sardines, herring, and oysters. Cod livers are delightfully mild and pack a wallop of vitamins A and D to boot. Primal-friendly sources of ALA include flax seeds, chia seeds, and walnuts. You also get some omega-3s in meat and eggs (chickens are often fed omega-enriched feed). Grass-finished beef and pastured eggs³¹ will deliver higher doses.

Although seafood is by far the best source of EPA and DHA, if you are vegetarian or vegan, you can get these important fatty acids from algal oil. Seaweed and chlorella also contain omega-3s, but nowhere near the quantities found in seafood.

How Much Do You Need?

The generally accepted advice is to aim for one to two servings per week of seafood, but there is no set recommended daily allowance (RDA) for ALA, EPA, or DHA. Generally, you’ll find recommendations to consume anywhere from 250 to 500mg per day of combined EPA+DHA. I developed an omega-3 formula with clean ingredients to make it easy to get sufficient EPA and DHA every day.

Does Your Omega-3:Omega-6 Ratio Matter?

In the body, omega-6s compete for space with omega-3s. Both can be incorporated into cell membranes, where they affect the membranes’ fluidity, permeability, and signaling pathways. Research shows that the amount of each in cell membranes is proportional to omega-3 and omega-6 consumption in the diet. An imbalance of omega-3 to omega-6 PUFAs can negatively affect how the cells—including in immune cells and neurons—function.³²

The primary omega-6 fatty acid is linoleic acid (LA). LA and the primary omega-3 ALA use the same enzymatic pathways to convert into longer-chain fatty acids: arachidonic acid (AA, in the case of LA) and EPA and DHA (in the case of ALA). High LA levels can crowd out the ALA and make it so that it can’t make the all-important EPA and DHA.

You can directly impact the amount of omega-3s and omega-6s in your tissues by changing your diet.³³ This, in turn, can affect your levels of inflammation and disease risk. For example, across cultures with diverse diets, greater intake of omega-6s is associated with having more omega-6 in the tissues and with greater incidence of cardiovascular disease. This effect is moderated by omega-3 intake. Across all levels of omega-6 intake, higher omega-3 consumption is associated with lower disease risk. The lower the omega-3 intake, the higher the risk.³⁴

Although some research suggests that the high ratio of omega-6 to omega-3 in modern diets puts people at risk for developing certain diseases such as heart disease and cancers,³⁵ Experts argue that our ancestors evolved with a diet that had approximately equal proportions of omega-3s and omega-6s.³⁶ Depending on whom you ask, modern diets may have a ratio of 1:10, 1:16, 1:20, or more!

I used to bang the drum about hitting the right omega-3:omega-6 ratio in your daily diet. In recent years I’ve backed off that stance somewhat. I still think modern diets like SAD are way too high in omega-6s, but the answer isn’t to pile on heaping servings of omega-3s to balance it and “correct” the ratio. The solution is to reduce consumption of omega-6s (mostly from refined seed and vegetable oils, and products containing those oils) while getting adequate omega-3s.

Should I Supplement With Fish Oil?

It is certainly possible to be deficient in omega-3s. Clinical deficiencies usually manifest as scaly rashes. Severe omega-3 deficiencies are rare in most parts of the world, though. Subclinical low omega-3 levels may manifest as brittle nails and hair, poor sleep, or mood disturbances.

Despite a mountain of evidence that omega-3s are essential for health, there is still no clear guidance about who exactly should supplement and how much. It seems to me that the best practice, and one I follow myself is: aim to get omega-3s from food, and supplement wisely as needed. In practice, this means I select grass-fed meat when I can, and I eat pastured eggs most days, and I eat a couple servings of small-oily fish every week. I take an omega-3 supplement most days, but I’ll skip that on the days when I eat fatty fish. Plus, I eat a lot of ALA-containing vegetables.

The other thing I do, of course, is limit my omega-6 consumption by avoiding refined seed and vegetable oils. I’m not overly concerned with omega-6s found in nuts, which I don’t eat in huge quantities anyway, or other whole foods.

For folks who are already eating a lot of omega-3-rich foods, further supplementation may not offer a ton of benefit.³⁷ If you’re not sure where you fall, you can ask your doctor for a blood test for omega-3 levels. You can also just track your food for a few days in an app like Cronometer that tells you how much you’re consuming.

Are There Any Downsides?

Perhaps. Some people have raised the concern that because they are polyunsaturated, omega-3s, especially in supplement form, are subject to rancidity and may cause oxidative stress. This speaks to the importance of sourcing your supplements from a reputable source. Store them according to instructions on the label and use them by their best-by dates. It’s another argument for prioritizing food sources as well.

Furthermore, it seems clear that more is not better, especially when it comes to supplementation. Excessive intake may lead to bleeding since EPA and DHA can reduce platelet aggregation, although this doesn’t seem to be a big risk for the average person. Nevertheless, the FDA recommends of cap of 3 grams EPA+DHA per day, with no more than 2 grams coming from supplements. Higher doses should only be taken with a doctor’s supervision.

In any case, these risks seem to me to be considerably less than the potential downsides of getting insufficient omega-3s. I still count omega-3s as a central player in overall health and healthy aging.