Omega-3 Fatty Acids: Benefits, Dosage, and Safety

What omega-3 fatty acids is

Omega-3 fatty acids are polyunsaturated fatty acids (PUFAs) that have a carbon-carbon double bond located three carbons from the methyl end of the chain. The three most studied are alpha-linolenic acid (ALA, an 18-carbon fatty acid found mainly in plant oils), and two long-chain (LC) marine omega-3s, eicosapentaenoic acid (EPA, 20 carbons) and docosahexaenoic acid (DHA, 22 carbons), found in fish and other seafood. ALA is an essential fatty acid, meaning the body cannot make it and must obtain it from the diet. The body can convert some ALA into EPA and then DHA, but this conversion (mainly in the liver) is very limited, with reported rates of less than 15 percent, so consuming EPA and DHA directly from food or supplements is the only practical way to raise their levels in the body.

What it does

• Serve as structural components of the phospholipids that form cell membranes, with DHA especially concentrated in the retina, brain, and sperm
• Provide a source of energy for the body
• Act as precursors to eicosanoids, signaling molecules with wide-ranging roles in the cardiovascular, pulmonary, immune, and endocrine systems
• Influence the balance of inflammatory signaling, since higher concentrations of EPA and DHA relative to arachidonic acid tip eicosanoid production toward less inflammatory activity
• ALA is an essential fatty acid that must be supplied by the diet

How much omega-3 fatty acids per day

These are population reference values from the NIH and the Dietary Reference Intakes. They are targets for healthy people, not personal prescriptions. The last column is the Tolerable Upper Intake Level, the most you should get from all sources combined.

Deficiency and who is at risk

Classic essential fatty acid deficiency, of either omega-3s or omega-6s, can cause rough, scaly skin and dermatitis. Plasma and tissue concentrations of DHA fall when an omega-3 deficiency is present. However, there are no known cut-off concentrations of DHA or EPA below which functional endpoints such as visual function, neural function, or immune response are impaired. Classic essential fatty acid deficiency in healthy people in the United States is virtually nonexistent.

Who may need more

• People who eat little or no fish or other seafood and want to raise EPA and DHA status
• Vegetarians and vegans, who typically rely on ALA and may choose algal-oil DHA/EPA supplements
• People with elevated triglycerides, for whom the American Heart Association suggests 2 to 4 g/day EPA plus DHA under a physician's care
• People with existing cardiovascular disease, who may be prescribed high-dose omega-3 preparations by a clinician (a medical decision, not self-treatment)
• Pregnant and breastfeeding women, whose AI for ALA is higher and who obtain DHA that passes into human milk

Food sources

ALA (plant sources): flaxseed oil (7.26 g per tbsp), chia seeds (5.06 g per ounce), English walnuts (2.57 g per ounce), whole flaxseed (2.35 g per tbsp), canola oil (1.28 g per tbsp), soybean oil (0.92 g per tbsp). EPA and DHA (marine sources): farmed Atlantic salmon (1.24 g DHA plus 0.59 g EPA per 3 ounces), wild Atlantic salmon (1.22 g DHA plus 0.35 g EPA), Atlantic herring (0.94 g DHA plus 0.77 g EPA), canned sardines (0.74 g DHA plus 0.45 g EPA), Atlantic mackerel (0.59 g DHA plus 0.43 g EPA), canned pink salmon (0.63 g DHA plus 0.28 g EPA), rainbow trout (0.44 g DHA plus 0.40 g EPA). Some eggs, yogurt, milk, juices, and soy beverages are fortified with DHA, and most U.S. infant formulas contain added DHA.

Forms and absorption

Long-chain omega-3 supplements come as fish oil, krill oil, cod liver oil (which also supplies vitamins A and D), and vegetarian algal oil. A typical fish oil capsule provides about 1,000 mg fish oil containing roughly 180 mg EPA and 120 mg DHA, though products vary widely. Chemical forms include natural triglycerides (the form in fish oil), free fatty acids, ethyl esters, re-esterified triglycerides, and phospholipids. Omega-3s as re-esterified triglycerides, natural triglycerides, and free fatty acids have somewhat higher bioavailability than ethyl esters, though all forms significantly raise plasma EPA and DHA. Krill oil supplies omega-3s mainly as phospholipids, with mixed evidence on whether bioavailability exceeds that of fish oil. Algal oil (typically triglyceride form) usually provides about 100 to 300 mg DHA, sometimes with EPA, and in a small study DHA bioavailability from algal oil matched that from cooked salmon. Check labels, since amounts of actual EPA and DHA differ from the stated oil weight.

Safety, excess and interactions

Too much

The IOM did not set a Tolerable Upper Intake Level, but noted that high doses of EPA and DHA (about 900 mg/day EPA plus 600 mg/day DHA or more for several weeks) might reduce immune function due to suppression of inflammatory responses, and that doses of 2 to 15 g/day EPA and/or DHA might increase bleeding time by reducing platelet aggregation. In the high-dose STRENGTH trial (4 g/day omega-3 carboxylic acid), the supplemented group had a higher incidence of atrial fibrillation. Reported side effects of supplements are usually mild: unpleasant taste, bad breath, bad-smelling sweat, headache, heartburn, nausea, stomach discomfort, and diarrhea. Omega-3 supplements have not been found to contain the methyl mercury present in some seafood, because it is removed during processing and purification.

Interactions to know

• Anticoagulant and antiplatelet medications (for example warfarin, aspirin, clopidogrel) and other blood-thinning herbs or supplements: because omega-3s can reduce platelet aggregation and prolong bleeding time, combining them may theoretically increase bleeding risk; clinical trials have generally shown prolonged bleeding time did not exceed normal limits or cause clinically significant bleeding, but periodic monitoring is advised
• High doses (roughly 900 mg/day EPA plus 600 mg/day DHA or more for several weeks) may suppress inflammatory immune responses and reduce immune function
• Prescription high-dose omega-3 products used to lower triglycerides should be taken only under medical supervision, since these are drug-strength doses

How status is measured

Omega-3 status is not routinely measured in clinical practice. When assessed, it can be measured as individual omega-3s in plasma or serum phospholipids expressed as a percentage of total phospholipid fatty acids (mean EPA plus DHA is about 3 to 4 percent in U.S. adults not taking supplements), but plasma values vary with the most recent meal. A more stable measure is the omega-3 index, the EPA plus DHA content of erythrocyte (red blood cell) membranes as a percentage of total erythrocyte fatty acids, which reflects intake over roughly the previous 120 days (about 3 to 5 percent in Western populations with low fish intake). No normal reference ranges have been formally established.

Regulated as a dietary supplement ingredient under DSHEA, not as a drug (supplements are not FDA-approved to diagnose, treat, cure, or prevent disease). The FDA approved a qualified health claim in 2004 stating that supportive but not conclusive research shows consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease, and specifies that supplement labels should not recommend more than 2 g/day of EPA and DHA. Separately, several high-dose EPA and EPA/DHA products (for example icosapent ethyl and omega-3 acid ethyl esters) are FDA-approved prescription drugs for treating very high triglycerides; those are distinct from over-the-counter supplements.

What the evidence supports

We grade the strength of evidence behind each common reason people take omega-3 fatty acids, mirroring how the NIH describes it.