omega-3 fatty acids
Summary
Omega-3 fatty acids are polyunsaturated fatty acids with the first double bond at the third carbon from the methyl (omega) end. They include ALA (plant-derived, essential), and EPA and DHA (marine-derived). They lower triglycerides, are precursors of less inflammatory eicosanoids, and DHA is key for retinal and neural development.
Detail
**Types and sources** - ALA (alpha-linolenic acid, 18:3): ESSENTIAL fatty acid; humans lack the desaturases (delta-12/delta-15) to insert double bonds beyond C9. Sources: flaxseed, chia, walnuts, canola/soybean oil. - EPA (20:5) and DHA (22:6): from fatty cold-water fish (salmon, mackerel, sardines, herring), fish oil, algae. Humans convert ALA to EPA/DHA inefficiently (<10%). - Linoleic acid (omega-6) is the other essential fatty acid; it is the precursor of arachidonic acid (conditionally essential if linoleic acid is deficient).
**Mechanism** - Compete with arachidonic acid (omega-6) for cyclooxygenase and lipoxygenase. This produces less inflammatory/less prothrombotic mediators (e.g., PGI3, TXA3, LTB5) instead of TXA2 and LTB4. - EPA/DHA give rise to specialized pro-resolving mediators (resolvins, protectins, maresins). - Lower hepatic VLDL/triglyceride synthesis and increase TG clearance (via PPAR-alpha activation, decreased DGAT/lipogenesis, increased lipoprotein lipase activity). - DHA is a major structural component of the retina (photoreceptors) and the CNS gray matter/neuronal membranes.
**Clinical significance** - Severe hypertriglyceridemia (TG >500 mg/dL): prescription omega-3 (EPA+DHA) lowers TG by about 20-50% and helps reduce pancreatitis risk. Can raise LDL slightly (DHA-containing products). - Icosapent ethyl (purified EPA ester): REDUCE-IT showed reduced cardiovascular events in statin-treated patients with elevated TG and ASCVD/high risk. Mixed-formulation or lower-dose trials (e.g., STRENGTH, OMEMI) were less convincing. Over-the-counter supplements are not shown to prevent primary cardiovascular disease (VITAL). - Risks: atrial fibrillation (dose-dependent, seen in higher-dose trials), fishy aftertaste/GI upset, a minor increase in bleeding tendency (antiplatelet effect, usually not clinically significant). - Pregnancy/infancy: DHA supports fetal brain and retinal development; recommended low-mercury fish intake (avoid shark, swordfish, king mackerel, tilefish). - Deficiency: scaly dermatitis, visual disturbances, peripheral neuropathy, and impaired growth/neurodevelopment (similar to essential fatty acid deficiency, which can occur in prolonged TPN without lipids and in fat malabsorption). - Other associations: modest benefit for rheumatoid arthritis symptoms; the evidence for depression and ADHD is limited.
**High-yield board points** - ALA = essential omega-3; EPA/DHA = marine, cardio/TG benefit. - Omega-3 lowers triglycerides; fibrates, niacin, and omega-3s are the TG-lowering drug classes. - Omega-3 competes with arachidonic acid, so it produces less inflammatory eicosanoids. - DHA is important in the retina and brain. - Trans fats and saturated fats raise LDL; omega-3s do not meaningfully lower LDL.
Note: trial data on omega-3 evolve; verify the latest guideline recommendations (AHA/ACC, ESC) for clinical use.
Sources
- First Aid for the USMLE Step 1 (Biochemistry: Nutrition; Pharmacology: Lipid-lowering agents)
- Lippincott Illustrated Reviews: Biochemistry (Fatty acid structure and essential fatty acids)
- Harrison's Principles of Internal Medicine (Disorders of lipoprotein metabolism)
- Bhatt DL et al. REDUCE-IT. N Engl J Med. 2019;380:11-22
- Manson JE et al. VITAL. N Engl J Med. 2019;380:23-32
- 2018 AHA/ACC Guideline on the Management of Blood Cholesterol
- UpToDate: Fish oil and omega-3 fatty acids
Reviewed by Medusa editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.