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Ingredient review

Omega-3 fatty acids (EPA/DHA)

Description

What is it?

Omega-3 fatty acids are polyunsaturated fatty acids that possess lipid-mediating and anti-inflammatory properties, and are essential for human health. (158) Two of the most important omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA found in supplements are most commonly derived from the livers of lean fish such as cod, and in the tissue of oily fish, including herring, mackerel, salmon, sardines, and tuna. (54) However, EPA and DHA are actually synthesized by the algae that are consumed by fish, not the fish themselves. A variety of supplements now exist, providing EPA and DHA from fish, algal, and other sources, though fish oils are predominantly used. (158)

General daily recommendations for omega-3s include the consumption of at least 1,000 mg total per day, providing a minimum combined sum of 250 mg of EPA and DHA. (139)(400) Most Americans do not typically meet current general dietary guidelines, even with supplementation. (278) EPA and DHA are believed to provide broad cardiovascular and neurological benefits, though their positive effects for clinical improvement in various conditions remain controversial. (351

Not be confused with: Alpha-linolenic acid (a separate omega-3 fatty acid found in plant-foods)

Main uses

Cardiometabolic disorders
Cognitive function and maintenance
Inflammatory/pain disorders
Neurological disorders
Prenatal and offspring health/development
Prevention of cardiovascular surgical complications
Psychological disorders
Renal disorders

Formulations

EPA/DHA source
Characteristics & bioavailability
Algal oil
Vegetarian/vegan source of EPA/DHA, with supplements typically high in DHA (211)
More environmentally friendly, sustainable, and may possess lower contaminant risk than fish oil (158)(186)
Relatively little research conducted on clinical efficacy to date
Krill oil
Predominantly phospholipid-bound (73)(380)
Relatively little research conducted on clinical efficacy to date
Natural fish oils
Bound to natural triglycerides and free fatty acids (73)
Relatively expensive to produce compared with processed ethyl ester forms, but may have greater stability (341)
Processed fish oils
Fish oils manufactured to EPA/DHA concentrates, either as ethyl ester-bound fish oils or re-esterified TGs (73)
Ethyl ester-bound fish oils bind ethanol to the free fatty acids of fish oils by removing their glycerol backbone (73)
Re-esterified TGs reconnect free fatty acids back to glycerol after ethyl esterification to re-promote absorption/metabolism (73)
Relative order of highest to lowest bioavailability
1. Krill oil: phospholipid-bound (78)(202)(213)(296)(320)
2. Processed fish oil: re-esterified TG-bound (108)(320)
3. Natural fish oil/algal oil: natural TG-bound (108)211)(307)
4. Natural fish oil/algal oil: free fatty acid-bound (88)(211)(270)(307)
5. Processed fish oil: ethyl ester-bound (88)(108)(213)(270)(320)

Dosing & administration

Adverse effects

It has been suggested that fish oil supplements increase the risk of bleeding due to their anti-thrombotic properties. (37) However, systematic reviews have not found this theory to be substantiated. (38)(365)(387) Another concern is the possible increased exposure to environmental toxins, such as mercury, polychlorinated biphenyls, or other organochlorines, though this may also be unsubstantiated. (242)(331) Higher incidence of gastrointestinal adverse effects may occur when combined with statins, (72) but not placebo, and are typically limited to mild-moderate severity. (367) Fishy tasting eructation is commonly reported with fish oil supplementation. (19)

Pharmacokinetics

Absorption

  • EPA and DHA bound to triglycerides require emulsification and hydrolysis via lingual, gastric, and pancreatic lipases into free fatty acids and mono-glycerols prior to incorporation into micelles and subsequent absorption in the small intestine
  • EPA/DHA bound to phospholipids are only hydrolyzed in the small intestine and may spontaneously form micelles for absorption
  • Triglycerides are resynthesized from free fatty acids, mono-glycerols, and phospholipids in enterocytes and packaged into chylomicrons for transport in the lymphatic system to the liver for redistribution within lipoprotein molecules (e.g., LDL or HDL) or as plasma phospholipids (178)(261)

Distribution

  • Widely distributed to phospholipid membranes, but particularly distributed to neural, retinal, heart, and brain tissues
  • Can be stored as triglycerides in adipose tissue
  • Highest distribution concentrations dose-dependently begin to plateau with one gram per day within approximately two weeks (23)(237)

Metabolism

  • May be β-oxidized (energy production), incorporated into phospholipid membranes of cells, consumed in the synthesis of eicosanoids (signaling molecules in inflammation, and cardiovascular regulation) or other lipid-inflammatory mediators such as resolvins or protectins (73)(345)

Excretion

  • Half-lives of plasma EPA and DHA are 37 and 48 hours, respectively (73)
  • Half-lives of EPA and DHA in platelet and mononuclear cell membranes are one to two months, providing better indication of long-term bioavailability than plasma  (73)(237)

References