In 1976, U.S. Senator George McGovern called a hearing to argue that the overconsumption of fat increases the risk of heart disease. This hearing propelled the low-fat craze in America, where eating any kind of fat was considered bad for your health. And while many of us did avoid bad fats in the process, we also missed out on healthy fats, including essential fatty acids like Omega-3 fatty acids. But what is Omega-3, exactly, and what are the benefits of Omega-3?
These healthy fats are now correlated with reduced risk of obesity and heart disease, and they confer protective effects against certain other diseases. For pregnant women, Omega-3 consumption is considered vital for proper fetal development. Adding to those attributes, these fatty acids may also play an important role in your gut health — the focus of this article. Omega-3s can influence the mucosal immune system in the gut and how your gut microbiome behaves. These changes could have substantial impacts on your gut function that reduce the risk of disease overall.
What is Omega-3?
Omega-3s are classified as an essential poly-unsaturated fatty acid (PUFA). Essential fatty acids are those that we cannot produce ourselves. We must therefore obtain Omega-3s from our diet or through supplementation as fish oil pills. While our diet can contain varying amounts of Omega-3s depending on the food we eat, fish oil supplements contain both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two types of Omega-3s. Regardless of the source, consuming Omega-3 fatty acids is correlated with various bodily benefits including improved gut health, reduced risk of heart failure, improved cognitive functioning and fetal brain development.
Omega-3 and intestinal immunity
Your immune system plays an important role in protecting your gut from harm. The early literature on Omega-3 fatty acids suggests that these PUFAs change how your immune system behaves in the gut. These changes protect your immune system from self-harm and strengthen its response appropriately.
- Eicosanoid Synthesis: Omega-3 PUFAs act as precursors of eicosanoids. Eicosanoids are a type of PUFA that is 20 carbon atoms long (eico means 20 in Greek). These compounds act as key immune system mediators, acting through diverse structures that respond to their presence to regulate inflammatory responses. These compounds also affect how your immune cells behave, including T-cells critical for responding to foreign substances called antigens. (The spike protein of the virus that causes COVID-19 is an example of an antigen.)
- Signal transduction: PUFAs can also impact how your cells respond to changes in their gut environment. Exposure to Omega-3s can impact gene expression profiles among macrophages, immune cells tasked with destroying invading bacteria. Omega-3s can also inhibit the NF-kB network, a central immune system pathway, through two molecules called resolvins and protectins. Increased activity of the NF-kB network is correlated with the production of molecules that drives inflammation in inflammatory bowel disease (IBD).
Omega-3 and gut health
We know that the gut microbiome plays a vital role in disease. Changes to the gut microbiome are linked with intestinal diseases such as inflammatory bowel diseases (IBD). The gut microbiome also produces short-chain fatty acids (SCFAs) after digesting the food we eat. These compounds impact the gut-brain axis and reduce the risk of obesity and cardiovascular disease (CVD). Reduced SCFA production caused by changes to the gut microbiome may increase the risk of intestinal disease.
The first studies investigating the impacts of Omega-3s on the gut microbiome were performed on mouse models. Early research showed that PUFAs in the gut impact how well lactic acid-producing bacteria like different Lactobacillus species can adhere to the mucus coating the large intestines. A 2013 study then revealed that providing obese mice with Omega-3s reverted the changes to Bifidobacterium and Enterobacteriales abundance observed after eating a high-fat diet.
The promise of Omega-3s to improve gut function has yet to translate into studies on human participants. Still, a few studies do show promise for the benefits of Omega-3s on the gut microbiome:
- A randomized, open-label, cross-over trial had 22 middle-aged, healthy participants take 4g of Omega-3 PUFA supplementation for 12 weeks. The study observed an increase in the relative abundance of Bifidobacterium, Roseburia, Lactobacillus and Clostridiaceae in fecal samples. Each of these species are capable of producing beneficial SCFAs.
- A 2017 study examining 876 middle-aged and elderly female twins showed a link between circulating Omega-3 levels and the composition of the gut microbiome. In particular, high levels of Omega-3 in the blood were correlated with high levels of N-carbamylglutamate, a compound associated with reduced oxidative stress in the gut.
- A 2020 study compared the effects of daily supplementation with 500 mg of Omega-3 versus 20g of inulin, a prebiotic fiber found in plants like chicory root. The study determined that although both supplements increased SCFA concentrations, they impacted the composition of the gut microbiome differently. While inulin supplementation increased the abundance of Bifidobacterium spp. and Lachnospiraceae, Omega-3 supplementation increased the abundance of bacteria belonging to the genera Coprococcus and Bacteroides. The clinical benefits exerted by impacting different sets of taxa require further exploration, but they do imply different sets of clinical impacts.
Many of the changes to the gut microbiome with Omega-3 supplementation are opposite to those associated with intestinal diseases. For instance, a 2011 study determined that decreased abundance of a specific Clostridium species and Bifidobacterium adolescentis has been observed among patients with Crohn’s Disease. However, even though Omega-3 treatment changes the abundance of bacterial taxa associated with GI diseases, no study demonstrates a causal association between Omega-3 supplementation and microbiome-mediated protection against intestinal diseases. Still, the results raise further questions about the impact of Omega-3s on the gut microbiome.
Can Omega-3 supplements and foods help with other diseases?
Research has shown that foods rich in Omega-3s or the best Omega-3 supplements have positive effects in a number of different diseases and bodily processes:
- Obesity: Omega-3 supplementation has been linked with reduced risk of obesity, including in young women. One way it may do so is by reducing the size of cells that store fat (adipocytes) in your body. Circulating Omega-3 molecules are also positively correlated with circulating levels of a hormone called adiponectin, which controls adipocyte activity. Increased adiponectin activity has been associated with reduced levels of proinflammatory molecules and with increasing the capacity of skeletal muscles to use glucose and fatty acids.
- CVD: Consuming Omega-3s can help reduce the risk of CVD. That’s why the American Heart Association continues to recommend the consumption of two 3 oz. servings of fatty fish per week for all Americans, including pregnant women (assuming the fish are low in mercury content). This recommendation is based on the landmark 2006 JAMA clinical review, which concluded that such a dietary recommendation reduces the risk of coronary death by 36%. More recently, a 2020 meta-analysis of 40 studies (including 135,267 participants) showed that Omega-3 supplementation is an effective strategy for the prevention of certain CVD outcomes, and that for CVD events and MI the protective effect appears to increase with dosage. Taking high doses of Omega-3s (> 3 g/day) is also correlated with reduced blood pressure among older and hypertensive patients. Additionally, Omega-3 consumption is correlated with reduced blood triglyceride levels, a risk factor for CVD. Nevertheless, a 2021 study showed that achieving high levels of circulating Omega-3s did not provide benefits or harms in a cohort of 13,078 patients at high cardiovascular risk relative to placebo. However, differences in patient populations could have played a role in these contrary results. This 2021 study featured only patients with high CVD risk and elevated triglyceride levels, whereas the 2020 study featured a population with diverse CVD risks. Since CVD covers a wide range of disorders, teasing out the variation in benefits for preventing adverse outcomes would provide more insights.
- Fetal development: Omega-3s are critical for proper fetal development. A study performed on 11,875 pregnant women showed that eating less than 340 g of seafood per week was associated with reduced communication, social development and fine motor scores among children. Similarly, a 2018 review analyzing 70 RCTs determined that Omega-3 consumption reduced the likelihood of women undergoing preterm births <37 weeks and <34 weeks.
- Anxiety: In our Gut Health And Anxiety report, we explored the theory that Omega-3 PUFAs could protect against anxiety symptoms. A 2018 study determined that taking at least 2,000 mg/day of Omega-3 PUFAs improved anxiety symptoms. However, this amount is 4 times the minimum recommended Omega-3 level necessary for maintaining overall health. Because no Omega-3s maximum daily allowance has been set, whether the benefits to anxiety are small relative to the dosage remains to be seen.
- Colorectal cancer (CRC): A 2014 study determined that increased Omega-3 and Omega-6 intake was inversely correlated with the risk for distal colon cancer, but not for proximal colon tumors. However, A 2019 study did not observe any difference in the number of polyps in the gut, a precursor to colorectal cancer, with Omega-3 supplementation. A broad survey of the data points to mixed results like these to be attributed to the characteristics of the people being tested. These factors include Omega-3 levels before treatment, ethnicity, inflammatory response levels from the blood, and tumor characteristics. Whether Omega-3s can be used alone or in combination with other anti-colorectal cancer therapies also remains to be seen.
- Diabetes: A 2015 meta-analysis of 20 randomized control (RCT) trials determined that Omega-3 supplementation does not correlate with total glucose levels. This finding was replicated in a subsequent 2019 systematic review. However, the consumption of Omega-3 fatty acids is correlated with reduced risk of type 2 diabetes among a predominantly Chinese cohort. This suggests that the benefits of omega-3 fatty acid consumption may be observed among specific ethnic populations. However, the lack of research on this topic remains a limitation for providing inclusive care for diabetes patients. More research would be needed to include people of specific ethnicities to confirm these findings.
Best sources of Omega-3
With the potential benefits of incorporating Omega-3s in our diets, what are the best foods for getting the Omega-3s you need to keep yourself healthy?:
- Fatty fish: Fatty fishes like sardines, mackerel, salmon, and herring contain high levels of Omega-3s. Additionally, they are also rich in important nutrients such as vitamins D and B12, calcium, iron, selenium, and phosphorus
- Soybeans: Soybeans are an excellent plant source of Omega-3s. Soybeans also provide a rich source of fiber, protein, and antioxidants.
- Nuts and seeds: Many kinds of nuts and seeds are rich in omega-3s, including walnuts, flaxseeds, peanuts and chia seeds. They are also rich in other important nutrients, including protein, fiber,, vitamins, and the minerals magnesium, potassium and zinc.
- Some vegetables and herbs: In addition to protein-based sources, some vegetables and herbs also contain Omega-3s. Seaweed and algae, along with edamame and brussels sprouts, provide a rich source of Omega-3s for those seeking to avoid meat-based foods in their diet. Other leafy green vegetables also provide Omega-3s in small amounts.
Omega-3s exert a number of different beneficial physiological effects. They strengthen the mucosal immune system in our guts, feed members of the microbiome that produce beneficial compounds like SCFAs, and protect against oxidative stress. Consumption of foods high in Omega-3s (like fatty fish, nuts and seeds) has been correlated with reduced risk of obesity and heart disease, and contributes protective effects against certain other diseases. For pregnant women, Omega-3 consumption is considered vital for proper fetal development, although clinicians warn against consuming those types of fatty fish that are high in mercury, like swordfish. While Omega-3s supplementation has a number of benefits, the research on such substances is still young and we don’t know the optimum Omega-3 supplementation for each disease, or for maintaining health generally.