Omega-3 Supplementation Guide PDF

Omega-3 fatty acids are essential fats that play critical roles in neurodevelopment, cognitive function, immune response, inflammation control, cardiovascular health, cancer prevention, and healthy aging. Several types of omega-3s exist, but the ones that have the greatest influence on human health...

Omega-3 fatty acids are essential fats that play critical roles in neurodevelopment, cognitive function, immune response, inflammation control, cardiovascular health, cancer prevention, and healthy aging. Several types of omega-3s exist, but the ones that have the greatest influence on human health are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and to a lesser degree, docosapentaenoic acid. Although omega-3s are present in many foods, especially nuts, seaweed, and fatty fish (like salmon, tuna, and mackerel), some people may require supplemental omega-3s to ensure they're getting enough. Omega-3 supplementation is a complex subject with a lot of confusion but a multitude of evidence shows that optimal omega-3 supplementation can positively impact human health and even counteract many age-related and chronic inflammatory processes and conditions, including cardiovascular disease, dementia, and autoimmunity. This guide will help you choose a quality omega-3 fatty acid supplement, determine the best dose for your needs, and answer your frequently asked questions about these essential nutrients. How to Choose A Quality Omega-3 Supplement There are many choices when selecting an omega-3 supplement. Choosing a quality product requires careful consideration of several important factors, including: Freshness: Aim for low rancidity Purity: Look for low contamination Form: Choose higher bioavailable forms Concentration: Opt for higher omega-3 concentrations relative to other fats and ingredients Each of these factors can influence the supplement's effectiveness and the extent to which it delivers the health benefits associated with omega-3 supplementation. Freshness Why is freshness a concern? Omega-3s are prone to oxidation, making them rancid and negating some of their beneficial effects. Choose a fresh product with low oxidation levels. How is freshness determined? Scientists determine omega-3 freshness by TOTOX, or “total oxidation." TOTOX approximates an omega-3's oxidation – how rancid it is – by adding two measures of rancidity: the peroxide value (the primary oxidation product) and the para-anisidine value (the sum of all secondary oxidation products). The Global Organization for EPA and DHA, a trade group for the omega-3 supplement industry, recommends that all omega-3 supplements have a TOTOX ≤ 26. However, several recent studies have found that many omega-3 supplements are highly oxidized, with more than half of those tested exceeding this figure. Look for products with a TOTOX ﹤10. Note: TOTOX oxidation measurements are primarily reliable with unflavored omega-3 products based on fish oil and it can be difficult to capture true oxidation in flavored fish-oil based products and krill oil/phospholipid omega-3 products. Which is worse: low omega-3 intake or oxidized supplementation? While omega-3 oxidation in supplements is common, there is limited clinical evidence of the long-term harmful effects of significantly oxidized omega-3 supplements due to ethical concerns. However, some clinical trials have demonstrated suboptimal effects of lipids and triglycerides from oxidized omega-3 products even in the short term. Therefore, selecting fish oil supplements with low levels of oxidation is prudent to ensure both safety and efficacy. Despite omega-3s' vulnerability to oxidation, evidence suggests oxidized omega-3 fatty acids can still perform healthy functions. Some omega-3 supplement manufacturers have improved the quality of omega-3 products by adding small amounts of antioxidants (e.g., rosemary extract or mixed tocopherols) to limit rancidity. The risks associated with NOT consuming omega-3s likely surpass those related to oxidation. Having low omega-3 levels is a risk factor for many chronic health conditions, including coronary heart disease, cardiac death, heart failure, and premature death, among others. While choosing the least oxidized supplement is advisable, prioritizing sufficient omega-3 intake is crucial. Purity Omega-3s are derived from natural products and may contain environmental contaminants, including mercury, polychlorinated biphenyls, dioxins, and others. Although the amount of toxins in omega-3 supplements is likely low, chronic exposure to these and other contaminants may cause long-term health complications. However, high-tech distillation processes like supercritical or advanced molecular distillation reduces the risk of heavy metal contamination. However, the highest quality omega-3 products today have close to or undetectable levels of environmental contaminants. Look for products with low contaminant levels. Form Omega-3s in over-the-counter or prescription supplements are available in various forms, depending on their extraction, processing methods, or natural occurrence. These forms include: Triglycerides: These occur naturally or through the re-esterification of ethyl esters; they have high bioavailability. Phospholipids: These occur naturally; they have high bioavailability. Ethyl esters: These are produced via molecular distillation; they have low bioavailability. Whereas most omega-3 fatty acids in fish are triglycerides and phospholipids, prescription omega-3 supplements are typically ethyl esters. The FDA regulates prescription supplements for safety and quality, but studies suggest they are not absorbed or integrated into cells as efficiently as omega-3s in triglyceride form. Unfortunately, total oxidation (TOTOX) is difficult to accurately measure in phospholipid form, making it challenging to choose a quality phospholipid supplement. Tip: Taking ethyl esters with a high-fat meal may triple their bioavailability. Concentration The concentration of omega-3 fatty acids in a supplement is important because it influences the product's effectiveness and the dose needed to achieve health benefits. Ideally, a high-quality omega-3 contains at least 80 percent omega-3 fatty acids, primarily EPA and DHA. The remainder typically consists of other fats and ingredients, including vitamins (such as vitamin E, an antioxidant), flavorings, preservatives, and "filler" oils, like soybean or safflower oil, which contain omega-6s and omega-9s. Omega-3 Quality Checklist Fresh: Low oxidation (TOTOX < 10) Pure: Free of contaminants and heavy metals Form: Triglyceride or phospholipid for optimal bioavailability Concentrated: > 80 percent omega-3 fatty acids How do you determine if your supplement makes the cut? To determine the quality of an omega-3 supplement, rely on third-party testing from NSF International or ConsumerLab (see Resources below). These organizations perform thorough testing to ensure the supplement matches its content claims and is free of harmful contaminants. In addition, the International Fish Oil Standards (IFOS) group can provide a detailed analysis of a product's purity and potency. Takeaway Ensure you choose a quality omega-3 supplement by selecting a third-party validated product in triglyceride or phospholipid form or opting for a prescription omega-3 product. Quality triglyceride products to consider (no affiliation): OmegaVia: Ultra-concentrated Omega-3 ○ TOTOX < 10 ○ High concentration, >75 percent Metagenics: Omegagenics EPA-DHA 1000  ○ TOTOX < 10 ○ High concentration, >75 percent Pure Encapsulations: One Omega ○ TOTOX < 14 ○ High concentration, >80 percent Carlson: Elite DHA Gems ○ TOTOX < 10 ○ DHA only Innovix Pharmaceuticals: Innovix Triple Strength ○ TOTOX 80 percent Vegan options DEVA: Vegan Omega-3 DHA-EPA 300 ○ TOTOX < 10 ○ Concentration varies Carlson: Vegetarian DHA ○ TOTOX < 10 ○ Concentration varies Note: These are just a few options. Many excellent omega-3 supplement products are available on the market. Be sure to periodically reassess the supplement you choose using the above checklist to ensure that new lots adhere to the same (or better) standard. How Much Omega-3 Should You Take? A good approach for determining how much omega-3 you should take is to check your current omega-3 levels – your Omega-3 Index – and tailor the dose based on those results. The Omega-3 Index The Omega-3 Index measures the percentage of omega-3 fatty acids in red blood cells, providing a reliable assessment of your long-term omega-3 intake. Developed by Dr. Bill Harris, one of the world's leading experts in omega-3s, this simple blood test is available through a home kit offered by OmegaQuant (no affiliation). Why does the Omega-3 Index matter? Research demonstrates that a higher Omega-3 Index reduces the risk of premature death from all causes by 35 percent. Higher indices also correlate with improved brain white and gray matter integrity – and subsequent enhanced executive function. However, lower Omega-3 Index scores are linked to higher red blood cell distribution width, indicating nutrient deficiency or disease. The Omega-3 Index is also a powerful predictor of heart disease, comparable to other well-established risk factors. Knowing your Omega-3 Index can help you make informed choices about your dietary and supplemental omega-3 intake. What’s the typical Omega-3 Index score? The average Omega-3 Index is about 4 percent in the U.S. and other Western countries, reflecting low dietary and supplemental omega-3 intake. However, research suggests that maintaining an Omega-3 Index between 8 and 11 percent maximizes health benefits, especially cardiovascular health. If your Omega-3 Index is low, you may want to consider supplementation. Note: Current American Heart Association guidelines suggest eating two servings of fatty fish weekly and do not recommend omega-3 supplements. However, this approach likely would not increase a low Omega-3 Index to desired levels. Does the Omega-3 Index reflect omega-3 levels in all tissues? While the Omega-3 Index generally reflects omega-3 concentrations in most of the body's tissues, including the heart and muscles, it might not fully represent levels in the brain. Interestingly, BDNF is a better marker of omega-3 levels in the brain. How often should you be tested? Because the Omega-3 Index reflects the concentration of omega-3s in your red blood cells, testing every four months – coinciding with the cells' life cycle – will provide the greatest insights into the effectiveness of your dietary and supplementation strategies. Learn more about the Omega-3 Index in this interview with Dr. Harris. How much should you take if your Omega-3 Index is low? There is no established dose for omega-3 supplementation. However, to reach the optimal Omega-3 Index range of 8 to 11 percent from a baseline of 4 percent, experts recommend consuming 1,750 to 2,500 milligrams (1.75 to 2 grams) of omega-3s daily. While higher doses of ethyl ester form greater than 2 grams daily may carry a slightly increased relative risk of arrhythmia in older people with cardiovascular risk factors, they may also provide qualitatively unique benefits, including immune system regulation, neurological support, muscle growth promotion, and heart protection. In one trial, elite athletes who consumed up to 3.6 grams of supplemental omega-3s daily experienced reduced pro-inflammatory cytokines, including IL-1B, and increased anti-inflammatory cytokines, including IL-10. Another trial demonstrated that 5 grams of supplemental omega-3s daily attenuated muscle disuse atrophy in young women after immobilization. The study's investigators posited that high-dose fish oil may increase protein synthesis rates in skeletal muscle. In a small study in which 33 healthy people with the APOE4 gene variant took at least 2 grams of DHA-rich omega-3 fatty acids daily along with a B-complex vitamin, DHA and EPA levels in their cerebrospinal fluid increased. Authors of a large-scale review found that 2 to 3 grams of omega-3 daily reduced systolic and diastolic blood pressure. Omega-3 fatty acids are considered safe, and clinical trials have demonstrated their safety at high intakes, with some trials providing up to 25 grams daily. However, it's important to note that the safety of consuming these omega-3 megadoses was assessed in a short-term clinical trial, and such high doses should be approached with caution and under medical supervision. Note: Your optimal omega-3 dose may differ considerably from that of your partner, friend, or family member. Many people carry genetic variants in the enzymes that metabolize fatty acids, influencing their omega-3 status. Takeaways There's no "standard" optimal dose for omega-3s. Doses above 2 grams daily may carry slight risks but can also provide considerable benefits, such as immune support and muscle growth. Optimal omega-3 doses can vary widely due to baseline (pre-supplemental) levels and genetic differences in fatty acid metabolism. Higher doses may reduce inflammation, protect against muscle atrophy, and enhance brain uptake of omega-3s. Frequently Asked Questions Are omega-3s from algae the same as those from fish or krill oil? Omega-3s from algae raise circulating omega-3 levels as efficiently as those derived from fish oil. However, they differ in terms of their content and cost-effectiveness. Algal-derived omega-3 supplements often: Consist mainly of DHA with little to no EPA, potentially diminishing their effectiveness for cardiovascular disease prevention. Have lower concentrations and smaller recommended doses than products derived from fish or krill oil – and end up costing you more in the long run. Is omega-3 from flaxseed or other plant sources such as hemp suitable as a replacement for marine-derived omega-3s? Plants like flaxseed, hemp, and walnuts contain the omega-3 ALA. The body converts ALA to EPA and DHA, but the conversion rate is remarkably low, with 0.2 to 8 percent of ALA converting to EPA and even less converting to DHA. Therefore, ALA might not be a suitable substitute for EPA and DHA. Although algae-based products provide a plant-based option to increase serum DHA levels effectively, they might not boost EPA. In addition, consuming ALA alone doesn't usually raise the Omega-3 Index above 8 percent. However, certain biological mechanisms may allow people who follow plant-based diets and consume ALA to reach adequate levels of EPA and DHA. For example, some hormones, such as estrogen, can enhance the efficiency of this conversion. (See FAQ “Are omega-3s from algae the same as those from fish or krill oil?“) Note: ALA is safe, and its consumption is associated with lower arrhythmogenic cardiomyopathy and decreased cardiovascular disease risk. Is there an optimal time to supplement omega-3 fatty acids? There are no guidelines for optimal “timing” of omega-3 fatty acid intake. However, some evidence suggests that EPA and DHA improve sleep quality and reduce the body's postprandial (post-meal) pro-inflammatory response. Sleep In a trial in which 84 adults consumed either EPA or DHA-rich oils before bedtime over 26 weeks, DHA-rich oil consumption improved sleep latency (the time it takes to fall asleep) and sleep efficiency but worsened other markers of subjective sleep quality. Postprandial inflammation Blood levels of lipopolysaccharide (LPS), an endotoxin found in the cell membranes of gut microbes and linked to an array of age-related diseases, increase after eating, promoting an immune response and inflammation. In a study where participants received low versus high doses of the prescription omega-3 Lovaza (1 gram EPA + DHA) before LPS exposure, those who took the high dose had a lower temperature increase (corresponding to a more appropriate immune response). These findings suggest that taking an omega-3 supplement during mealtime may blunt post-meal increases in LPS, thereby attenuating postprandial inflammation. Note: While there is no strong evidence advocating for an optimal time to take omega-3 supplements, taking them with a fatty meal improves their metabolism. Should I refrigerate omega-3 capsules? Omega-3 fatty acids are particularly susceptible to oxidation, which accelerates at higher temperatures. Encapsulation provides some protection against oxidation, but non-encapsulated products (liquid forms) may be more vulnerable. Therefore, it is a best practice and good general rule of thumb to refrigerate all omega-3 supplements. Interestingly, research indicates that neither the expiration date nor the manufacture date on omega-3 supplements reliably predicts rancidity levels, probably because of the heterogeneity between products. Takeaway Omega-3 fatty acids frozen or refrigerated are safe, beneficial, and not associated with adverse effects. If you buy an omega-3 oil, refrigerate it immediately to slow oxidation. However, there is little evidence that refrigerating your omega-3 capsules will prolong their shelf life or lower their rancidity. Does omega-3 cause prostate cancer? In 2013, the SELECT trial identified a marked increase in prostate cancer risk linked to omega-3 supplementation. This finding represents a potentially spurious association, with approximately a 0.5 percent elevation in omega-3 levels in red blood cell membranes correlating with an increased risk of prostate cancer. While two large-scale reviews have corroborated this finding, others have strongly refuted it. An examination of tissue samples collected from men with prostate cancer revealed that high doses of omega-3 had no discernible effects on proliferation. Additionally, the associated risk seems minimal and is outweighed by the reduced risk of cardiovascular disease and arrhythmogenic cardiomyopathy. Does omega-3 supplementation cause atrial fibrillation (Afib)? Although some research indicates that omega-3 supplementation may increase the relative risk of developing atrial fibrillation (Afib), it's important to distinguish this from the absolute risk. Relative risk considers the increase in risk compared to a baseline or control group – it shows the proportionate change in risk between two conditions. In this case, while there may be a higher relative risk with omega-3 use, the absolute risk, which reflects the actual probability of an individual developing Afib over a specific period, remains low. This means that despite the increased relative risk, the overall likelihood of developing Afib due to omega-3 supplementation is still relatively small. Several possible mechanisms that may be driving this association: Form (ethyl ester versus triglyceride): Ethyl esters slow the absorption of omega-3, facilitating their oxidation. The incorporation of oxidized lipids into cardiac myocytes might adversely affect atrial signaling. Oxidative stress is a likely contributor to the development of Afib. Dose: Afib is associated with high-dose omega-3 supplementation. In trials that have documented an increased incidence of Afib, the risk manifested at doses of at least 1.8 grams per day (OMEMI trial) and was more common at 4 grams per day (STRENGTH trial). Notably, the VITAL trial used a dose of 1 gram daily of Lovaza (omega-3 ethyl ester) and did not observe a significant increase in Afib. A combination of these factors or something else. While scientists have not pinpointed the exact mechanism underpinning this association, several factors should be considered, including the possibility that high dosing of omega-3s in vulnerable, older adults (such as those in the clinical trials) is the primary driver. Similarly, it could be that phospholipids, the primary form of omega-3s in fish but not supplements, do not carry the same risk for Afib. Finally, one must consider that fish (as opposed to supplements) contain other compounds that stabilize the oil, such as naturally occurring carotenoids. Cause for reassurance Afib is commonly associated with risk factors such as hypertension, diabetes, and cardiovascular issues, primarily posing concerns due to its influence on stroke risk. In randomized controlled trials that noted a slight increase in relative Afib risk, the absolute risk increase remained low without a corresponding rise in stroke risk. For instance, in the STRENGTH trial, adult participants with high cardiovascular risk factors experienced only a 0.9 percent increase in their absolute Afib risk without any increased stroke risk. Similarly, in the REDUCE-IT trial, adults over the age of 45 with existing cardiovascular diseases saw a 1.4 percent increase in their absolute Afib risk, yet benefited from a 26 percent reduction in nonfatal stroke risk compared to the placebo group. Furthermore, in the OMEMI trial, elderly adults post-acute heart attack – another high-risk group for Afib – had a 3.2 percent increase in their absolute Afib risk but no heightened stroke risk. Collectively, the increased absolute Afib risk with high dose omega-3s in people with an increased risk for Afib due to cardiovascular risk factors is still low, and robust evidence suggests that omega-3 supplementation effectively lowers the stroke risk, challenging the notion that they entail the same level of harm and death risk typically associated with Afib. Similar intricate relationships exist in other aspects of healthy lifestyle behaviors. For example, certain categories of elite athletes face up to a fivefold increase in Afib risk despite generally experiencing a substantial reduction in cardiovascular mortality risk. Minimizing the risk of atrial fibrillation As the risks of cardiovascular disease increase, the likelihood of experiencing Afib increases, and even exceeding recommended exercise levels may increase a person's risk of developing the condition. A conservative omega-3 dose, such as 2 grams per day, has been shown to raise the Omega-3 Index to the 8 percent range. Protective factors Interestingly, numerous studies have indicated that antioxidant therapy can potentially prevent or delay the onset of Afib. According to one meta-analysis, the intake of N-acetylcysteine (an amino acid), vitamin C, and omega-3 fatty acids reduced the risk of postoperative Afib following cardiac surgery. Low doses While lower doses of omega-3 supplementation may not pose the same risks, it's worth noting that some of the more potent effects of omega-3s, such as muscle-preserving effects and immunomodulation, may not be as pronounced. However, it seems prudent that some people with a high Afib risk should approach high-dose omega-3 intake with caution. Increasing dietary omega-3 intake from fatty fish Although fish oil supplementation has been linked to Afib, there are no documented associations between eating fish and Afib. In fact, evidence suggests that people who eat more than five servings of fatty fish per week are 31 percent less likely to develop Afib than non-fish eaters. Resources: Want more information? Check out these resources. Product safety and analysis ConsumerLab.com iFOS Labdoor Omega-3 Index testing Omegaquant FMF articles and interviews Omega-3 Fatty Acids (overview topic article) Omega-3 Index (stub article) Bill Harris, PhD, on the Omega-3 Index, Increasing Omega-3 to Improve Longevity & Heart Disease Risk Chris McGlory, PhD, on the Anabolic Potential of Omega-3 Fatty Acids