omega-3 fatty acid

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Omega-3 fatty acids (omega-3s) have a carbon–carbon double bond located three carbons from the methyl end of the chain. Omega-3s, sometimes referred to as n-3s, are present in certain foods such as flaxseed and fish as well as dietary supplements such as fish oil. Several different omega-3s exist, but the majority of scientific research focuses on three: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA contains 18 carbon atoms, whereas EPA and DHA are considered long-chain (LC) omega-3s because EPA contains 20 carbons and DHA contains 22.

NIH Office of Dietary Supplements (ODS) ↗ · Källdatum saknas · Källans villkor

Omega-3 fatty acids (omega-3s) have a carbon–carbon double bond located three carbons from the methyl end of the chain.

NIH Office of Dietary Supplements (ODS) ↗ · Källdatum saknas · Källans villkor

Omega-3s, sometimes referred to as n-3s, are present in certain foods such as flaxseed and fish as well as dietary supplements such as fish oil.

NIH Office of Dietary Supplements (ODS) ↗ · Källdatum saknas · Källans villkor

ALA is present in plant oils, such as flaxseed, soybean, and canola oils [3]. DHA and EPA are present in fish, fish oils, and krill oils, but they are originally synthesized by microalgae at the base of the marine food chain, not by the fish. As microalgae move up the food chain, fish acquire the omega-3s and accumulate them in their tissues [3].

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Many observational studies link higher intakes of fish and other seafood with improved health outcomes. However, it is difficult to ascertain whether the benefits are due to the omega-3 content of the seafood (which varies among species), other components in the seafood, the substitution of seafood for other less healthful foods, other healthful behaviors, or a combination of these factors. Data from randomized clinical trials are needed to shed light on these questions.

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Several subsequent clinical trials, however, had largely null findings [58-60]. For example, the 2012 Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial included 12,536 patients who had diabetes or a high risk of diabetes and a high risk of cardiovascular events. Supplementation with 1 g/day omega-3s (375 mg DHA and 465 mg EPA) for about 6 years significantly lowered triglyceride levels but had no effect on risk of myocardial infarction, stroke, or death from cardiovascular causes in comparison with placebo [59]. Similarly, in the 2010 Alpha Omega Trial, low-dose EPA and DHA supplementation (150 mg DHA and 226 mg EPA daily, supplied in a margarine) for 40 months also failed to reduce the rate of major cardiovascular events in comparison with placebo among 4,837 older men and women who had previously experienced a myocardial infarction and were receiving antihypertensive, antithrombotic, and/or lipid-lowering medications [60].

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A subsequent 2020 clinical trial known as STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) found no significant CVD benefits with Epanova, a high-dose, prescription form of omega-3s containing EPA and DHA in a carboxylic acid form (omega-3 CA) [64]. STRENGTH included 13,078 participants from 22 countries (mean age 62.5 years) at high cardiovascular risk, including hypertriglyceridemia, low HDL cholesterol, diabetes, and established CVD. Participants received either 4 g/day omega-3 CA or a placebo of corn oil in addition to their usual therapies, including statins, for a projected trial duration of 4.5 years. However, the trial was stopped after participants were treated for a median of about 3.5 years when the probability of benefit from omega-3 CA appeared low and the supplemented group had a higher incidence of atrial fibrillation. Omega-3 CA did not significantly reduce the composite end point of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.

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The IOM did not establish a UL for any omega-3s, although it noted that high doses of DHA and/or EPA (900 mg/day of EPA plus 600 mg/day DHA or more for several weeks) might reduce immune function due to suppression of inflammatory responses. Doses of 2–15 g/day EPA and/or DHA might also increase bleeding time by reducing platelet aggregation [5]. However, according to the European Food Safety Authority, long-term consumption of EPA and DHA supplements at combined doses of up to about 5 g/day appears to be safe [195]. It noted that these doses have not been shown to cause bleeding problems or affect immune function, glucose homeostasis, or lipid peroxidation. Similarly, FDA has concluded that dietary supplements providing no more than 5 g/day EPA and DHA are safe when used as recommended [196]. Two large clinical trials completed after these assessments found that taking 4 g/day of omega-3 supplements for several years slightly increased the risk of atrial fibrillation in people with CVD or at high risk of CVD [63,64].

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Commonly reported side effects of omega-3 supplements are usually mild. These include unpleasant taste, bad breath, heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat [161,190].