Why omega 3s are crucial to strong metabolic health

Omega-3 fatty acids improve cellular health, help reduce inflammation and promote metabolic health. Here's the science behind them and how you can get more.

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Article highlights

  • Omega-3 fatty acids are key elements of cells and metabolic pathways. They come in three forms: alpha-linolenic fatty acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). All three are part of a metabolic pathway in which ALA is converted to EPA and DHA.
  • ALA is considered an “essential” omega-3 fatty acid because the body can’t make it independently and must obtain it through foods, including olive oil, seeds, and nuts. EPA and DHA are readily available in food, especially seafood.
  • Getting enough omega-3s limits the impact of omega-6s, another fatty acid that is associated with inflammation. At a ratio of 16:1, the Western diet typically contains too many omega-6s and not enough omega-3s.
  • Adequate omega-3 intake seems to be associated with less inflammation as well as protective effects against cardiovascular disease and depression.
  • TAKEAWAY: Making sure the body gets enough omega-3s through diet helps maintain metabolic health and reduce inflammation.

Omega-3s are everywhere on food packaging, from milk to eggs to pizza. But many of us probably don’t appreciate why they’re so important or how to get them (hint: it’s not through packaged foods!), let alone how many we need.

Omega-3 fatty acids are a crucial building block of our cells and play a role in several processes at the core of metabolic fitness. And, it turns out, most of us may not be getting enough.

What Are Omega-3 Fatty Acids?

Omega-3s are a type of fatty acid, the building block of all fats. Fats, in turn, are nutrients that are essential to the structure of every cell in the body and have a hand in all aspects of health and disease. They also play diverse roles as signaling precursors that allow intercellular communication and even make up the oil on your skin.

The human diet typically includes at least 20 different types of fatty acids, such as saturated, monounsaturated, and polyunsaturated fatty acids. These names refer to the chemical structure of the molecule: Saturated fatty acids have single bonds between their carbon molecules, while unsaturated fatty acids have one or more double bonds (monounsaturated or polyunsaturated, respectively). The chemical structure of a fatty acid determines its state at room temperature. Saturated fats (like most animal fats) are usually solid, while unsaturated fats (like most plant-based oils) are generally liquid.

The body needs all types of fatty acids to function properly. It can synthesize many of them in the liver from the raw materials it gets elsewhere in your diet. But two polyunsaturated fats—omega-3 alpha-linolenic fatty acid (ALA) and omega-6 fatty linoleic acid (LA)—are considered “essential” fatty acids, which means that the body can’t make them on its own. That’s why it’s essential that you get enough of each through your food.

ALA is just one of the three primary forms of omega-3 fatty acids. The other two are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA is found in plants, especially olive oil, seeds, and nuts, and it is typically the most abundant omega-3 fatty acid in American diets. But for the body to use ALA, it must be converted into EPA and DHA. All three of these omega-3 fatty acids are part of a metabolic pathway in which a series of enzymatic reactions drive this conversion. You can also get EPA and DHA directly from food, mainly seafood.

Omega-3s are often referred to as a “good fat” that protects against insulin resistance and prevents plaque buildup in the arteries. They are a fundamental part of all cell membranes and are found at especially high levels in some tissues. For example, in parts of the retina, omega-3s make up about 30% of all fatty acids in the cell membrane. In cells throughout the body, omega-3s serve as the basis of cell receptors, facilitating communication between cells. They also keep arteries elastic, which wards off cardiovascular disease—more on that later.

What’s the Difference Between Omega-3s and Omega-6s?

Omega-3s and omega-6s are both polyunsaturated fatty acids. They get their name from the position of the double bond in their chemical structure. In omega-3s, the double bond is three atoms away from the final methyl group; in omega-6s, the double bond is six atoms away. The American diet typically contains too many omega-6 fatty acids—which are found in refined seed oils, grains, and grain-fed meat—and not enough omega-3s. Omega-3s and omega-6s use the same pathways for metabolism and need the same limited enzymes to do so. Although you need omega-3s and omega-6s for cellular function, having higher levels of omega-6s compared to omega-3s can promote inflammation.

 

Both omega-3s and omega-6s are precursors—molecules involved in reactions that form a different molecule—for signaling molecules called eicosanoids, including prostaglandins (PGs). Each is used to create different PGs: Omega-3s are precursors for PG1, which reduces inflammation, while omega-6s, in contrast, produce pro-inflammatory PG2s. Since the two types of fatty acids compete for the enzymes that make these conversions happen, having more omega-3s in the body means that more of those enzymes will be used in the production of anti-inflammatory PG1s, and fewer will be available to convert omega-6 fatty acids into inflammatory PG2.

Getting ample omega-3s blocks the damage that too many omega-6s can do, which is why it’s essential to keep a good omega-3 to omega-6 ratio. Research has established that humans evolved on a diet in which the ratio was roughly 1:1. The proportion of omega-6s in Western diets increased sharply during the 20th century as people began to consume more soybean oil, which is high in linoleic acid (an omega-6 fatty acid).  Today, the standard Western diet has an omega-6 to omega-3 ratio of roughly 16:1. Estimates for the ideal ratio vary, but a lower ratio— closer to what humans are genetically equipped to live with—is generally considered more metabolically healthy.

How Omega-3s Affect Metabolic Health

Anti-inflammatory capabilities

The human body uses temporary states of inflammation to fight off disease, but chronic low-grade inflammation is a hallmark of metabolic syndrome. It’s also the root cause of many diseases, including cardiovascular disease, cancer, and neurological diseases. In addition to keeping pro-inflammatory PG2s at bay and promoting the production of anti-inflammatory PG1, omega-3s combat inflammation in other ways.

Omega-3s act inside cells to change gene expression in a way that disrupts pro-inflammatory pathways involving proteins like NF-kappa-B (NF-kB) and reduces the production of pro-inflammatory cytokines, other proteins involved in cell signaling.

Omega-3s—especially EPA and DHA—also limit the production of other pro-inflammatory molecules, like thromboxanes and leukotrienes. The omega-6 metabolic pathway that produces these inflammatory molecules competes for the same limited enzymes used by the omega-3 pathway, so when there’s an abundance of omega-3s, the omega-6 pathway cannot proceed. This competition results in fewer pro-inflammatory molecules and the production of more anti-inflammatory mediators.

NSAIDs like ibuprofen reduce inflammation through the same pathway to reduce inflammation. These drugs block COX-2 activity outright, preventing the enzyme from making the precursors to pro-inflammatory molecules. Reducing inflammation by getting more omega-3s in your diet doesn’t work as quickly as taking NSAIDs. However, it still has a significant effect on decreasing systemic inflammation and the diseases that stem from it.

Insulin resistance

Omega-3s are also part of several pathways that regulate insulin sensitivity, but their real-world effect on insulin in humans is still unproven; much of the research here is in limited studies or animal models. One small study showed that increasing omega-3 intake was correlated with significantly higher insulin sensitivity in overweight middle-aged men. Those who ate the highest amounts of omega-3s had 43% higher insulin sensitivity compared to those who ate the least. Their fasting insulin concentrations were also 25% lower.

Several mechanisms could explain how omega-3s might impact insulin sensitivity. One is that omega-3s counter the inflammatory effect of the amino acid homocysteine, which plays a role in insulin resistance and is found at high levels in people with Type 2 diabetes. A mouse study found that treatment with omega-3s in the form of fish oil supplements reduced insulin resistance induced by high levels of homocysteine. The authors hypothesized that omega-3 treatment changed the lipid profiles of the mice in a way that decreased the inflammation caused by homocysteine, which in turn reduced insulin resistance.

Another mechanism is that omega-3s act upon the endoplasmic reticulum (ER), the part of the cell where proteins are produced. ER stress, a condition where the ER is unable to fold proteins properly, is associated with diabetes. It’s thought that ER stress activates the inflammatory pathways that keep insulin from regulating glucose. A mouse study found that omega-3s help prevent this stress, restoring insulin sensitivity.

Other researchers have found that EPA and DHA could have a protective effect against insulin resistance brought on by a high-fat diet. As a study in rodents illustrates, a high-fat diet decreases the activity of an enzyme called PI3 kinase, which helps maintain the presence of a glucose transporter protein called GLUT4 in the muscles and fat. GLUT4 is important because it reduces blood glucose levels by bringing glucose into cells. EPA and DHA ensure that PI3 kinase is active, which ensures GLUT4 can continue to maintain blood glucose levels.

So far, we don’t have large-scale human studies to demonstrate whether these mechanisms translate to improved glucose profiles in humans. Two meta-analyses on the effect of omega-3 supplements on metabolic markers in people with diabetes found little impact on glucose control. Both did demonstrate reduced triglycerides, which is vital for metabolic health.

Other Conditions Related to Omega-3s

Cardiovascular disease

The anti-inflammatory effect of omega-3s is important for cardiovascular health. Omega-3s keep artery walls flexible and prevent clotting and plaque from clogging arteries.

Omega-3s are often touted for their ability to lower LDL cholesterol, but the effects of EPA and DHA on cholesterol levels are not fully understood. Research has produced conflicting results: While a recent interventional study on DHA alone found that supplementation with DHA was associated with a reduction in LDL cholesterol, an older pooled analysis found that DHA increased both LDL cholesterol and “good” HDL cholesterol and that EPA didn’t appear to affect either.

While the evidence that omega-3s support cardiovascular health is clear, there’s conflicting evidence about the ability of omega-3 supplementation to prevent cardiovascular events like heart attack, stroke, or death. Nevertheless, they are still used to treat hypertriglyceridemia––abnormal amounts of triglycerides in the blood, which can clog and harden arteries, leading to an increased risk of the cardiovascular events mentioned above. EPA and DHA are thought to increase the activity of an enzyme called lipoprotein lipase, which breaks down triglycerides. They also prevent plaque buildup in the arteries by reducing the number of pro-inflammatory cytokines in the arterial wall.

Both omega-3s and omega-6s are also precursors for a group of fatty acid metabolites called oxylipins, which help regulate biological functions, including inflammation, the constriction and relaxation of blood vessels, and blood clotting. Other research has shown that EPA and DHA can “reprogram” the metabolism of triglyceride-rich lipoproteins (TRLs)––which means that it changes the way the cells consume energy. TRLs transport triglycerides between tissues. Increased TRL is linked to cardiovascular disease, and keeping them in check may be another way omega-3s reduce inflammation and keep plaque from accumulating on artery walls.

Depression

Omega-3s are often touted for their beneficial effects on brain health. Even though EPA is not abundant in the brain, it can rapidly cross the blood-brain barrier as a free fatty acid. Low amounts of EPA in the blood have been linked with depression, with one possible explanation being that they keep inflammation low. One meta-analysis found that a daily dose of one gram or less of omega-3s made up of at least 60% EPA can improve depression, perhaps because of its ability to curb pro-inflammatory cytokines.

Omega-3s are shown to be neuroprotective, helping maintain the health of neurons and their communication pathways in the brain. They’ve also been shown to influence brain development in infants and children: One study, for example, found higher cognitive ability in infants whose mothers ate more fish during pregnancy, while another found higher IQ in infants whose mothers took omega-3 supplements when pregnant or breastfeeding.

How to Get Omega-3s

Our bodies don’t use all omega-3 fatty acids the same way, and it’s essential to understand the differences when choosing how we get them. Whether you get your omega-3s from fish, fish oil supplements, or omega-3-fortified foods, research shows that increasing your intake of these fatty acids can lead to measurable changes in the make-up of omega-3s in your cellular membranes within days of consuming them. But specific sources are richer in bioavailable omega-3s—the kind that the body can use readily—than others.

Coldwater fish are by far the richest source of bioavailable EPA and DHA, but levels vary a lot between species. Farmed Atlantic salmon is at the top of the list, with about 1.24 grams of DHA and 0.59 grams of EPA in every 3 ounces. The same amount of Atlantic herring has 0.94 grams of DHA and 0.77 grams of EPA, while an equal amount of sardines has roughly 0.74 grams of DHA and 0.45 grams of EPA. Mackerel, canned pink salmon, rainbow trout, oysters, and seabass are good sources of EPA and DHA. Quality eggs (go for pasture-raised) can also be a source of EPA.

ALA is an omega-3, but the body must convert it to EPA and DHA before using it. This process leads to only a small amount of EPA and DHA because most ALA is used for energy before it can be converted. Only about 5% of ALA is converted to EPA and 1% to DHA. According to the National Institutes of Health, getting EPA and DHA from food “is the only practical way to increase levels of these omega-3 fatty acids in your body.” In short, don’t rely on ALAs alone to meet your omega-3 intake, but getting some through your diet doesn’t hurt.

Flaxseed oil is a common source of ALA. An ounce of chia seeds has more than 5 grams of ALA per serving. Edamame has almost 0.3 grams per half-cup, and black walnuts have about 0.76 grams of ALA per ounce.

Small amounts of omega-3s are found in beef, pork, and poultry. Fish oil supplements typically contain 30-50% omega-3s by weight. Even if you don’t eat meat, you can get enough omega-3s from plant-based foods, especially those from the sea. Some types of seaweed, in particular Calliblepharis jubata and Undaria pinnatifida, are not only high in EPA and DHA but also have a low omega-6 to omega-3 ratio. 

One of the best ways to keep omega-6s in check is to avoid processed foods, including those processed using oil. Swap refined seed and vegetable oils for oils rich in omega-3s, like olive oil. Grain-fed meat is also a rich source of omega-6s, so go for grass-fed when you can.

According to the National Institutes of Health, men should aim to get at least 1.6 grams of ALA daily, and women should get 1.1 grams. The U.S. Department of Agriculture Dietary Guidelines recommend getting an average of 250 mg of combined EPA and DHA per day.