Introduction
Fish oil is a dietary supplement derived from the tissues of oily fish, primarily containing omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). While not classified as a pharmaceutical drug by the FDA, prescription formulations (such as Lovaza, Vascepa, and Epanova) are approved for specific medical indications. This monograph focuses on the clinical applications of omega-3 fatty acids from fish oil sources.
Mechanism of Action
The primary active components of fish oil are EPA and DHA, which exert multiple physiological effects:
- Incorporation into cell membranes, increasing membrane fluidity
- Modulation of eicosanoid production (decreased thromboxane A2, prostaglandin E2)
- Reduction of triglyceride synthesis through decreased hepatic very low-density lipoprotein (VLDL) production
- Anti-inflammatory effects via inhibition of nuclear factor kappa B (NF-κB) pathway
- Antiplatelet effects through reduced platelet aggregation
- Potential antiarrhythmic effects on cardiac myocytes
Indications
FDA-approved indications:- Hypertriglyceridemia (≥500 mg/dL) - prescription formulations only
- Secondary cardiovascular risk reduction (specific prescription formulations)
- Rheumatoid arthritis (symptom management)
- Mild cognitive impairment/dementia prevention
- Dry eye syndrome
- Depression adjunctive therapy
- Inflammatory conditions
Dosage and Administration
Prescription formulations:- Icosapent ethyl (Vascepa): 4 g daily (2 g twice daily with food)
- Omega-3-acid ethyl esters (Lovaza): 4 g daily (single or divided doses)
- Typical range: 1-4 g daily of combined EPA/DHA
- Cardiovascular health: 1 g daily of combined EPA/DHA
- Hypertriglyceridemia: 2-4 g daily under medical supervision
- Take with meals to enhance absorption and reduce gastrointestinal effects
- Store in cool, dark place to prevent oxidation
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use caution with severe impairment
- Pediatrics: Safety not established for prescription formulations
- Pregnancy: Generally considered safe, but consult healthcare provider
Pharmacokinetics
Absorption: EPA and DHA are absorbed in the small intestine via passive diffusion, enhanced by dietary fat. Bioavailability varies by formulation. Distribution: Incorporated into phospholipids of cell membranes throughout the body. Crosses blood-brain barrier and placenta. Metabolism: Undergoes beta-oxidation in mitochondria and peroxisomes. Metabolized via cyclooxygenase and lipoxygenase pathways to various eicosanoids. Elimination: Half-life of incorporated fatty acids is several weeks. Eliminated primarily as carbon dioxide via respiration and in feces.Contraindications
- Hypersensitivity to fish or shellfish (depending on source)
- Known allergy to any component of specific formulations
- Use with caution in patients with fish allergies (cross-reactivity possible)
Warnings and Precautions
- Bleeding risk: May prolong bleeding time; use caution with anticoagulant therapy
- Atrial fibrillation: Some studies suggest increased risk in certain populations
- Diabetes: May worsen glycemic control in some patients
- Liver function: Monitor liver enzymes periodically with high doses
- Oxidation: Rancid fish oil may produce harmful oxidation products
- Vitamin content: Some formulations contain vitamins A and D; monitor for toxicity
Drug Interactions
Anticoagulants/Antiplatelets: (Warfarin, aspirin, clopidogrel) - Increased bleeding risk Antihypertensives: Possible additive blood pressure lowering effects Orlistat: May decrease absorption of omega-3 fatty acids Cytochrome P450 substrates: Theoretical potential for interaction, but clinical significance unclearAdverse Effects
Common (>1%):- Fishy aftertaste/eructation
- Gastrointestinal discomfort (dyspepsia, nausea)
- Diarrhea
- Rash
- Significant bleeding episodes
- Allergic reactions
- Pancreatitis (at very high doses)
- Worsening of atrial fibrillation
Monitoring Parameters
- Fasting lipid profile (baseline and periodically)
- Liver function tests (with high-dose therapy)
- Hemoglobin A1c in diabetic patients
- Bleeding parameters in patients on anticoagulants
- Body weight and nutritional status
- Allergic reactions in susceptible individuals
Patient Education
- Take with meals to reduce gastrointestinal side effects
- Report any unusual bleeding or bruising
- Be aware of potential fishy aftertaste
- Store properly to prevent rancidity
- Choose products with third-party verification for purity
- Do not exceed recommended doses without medical supervision
- Inform all healthcare providers about fish oil supplementation
- Understand that effects may take several weeks to months
References
1. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation. 2019;140(12):e673-e691.
2. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22.
3. National Institutes of Health Office of Dietary Supplements. Omega-3 Fatty Acids Fact Sheet for Health Professionals. Updated June 2022.
4. Weitz D, Weintraub H, Fisher E, Schwartzbard AZ. Fish oil for the treatment of cardiovascular disease. Cardiol Rev. 2010;18(5):258-263.
5. Mozaffarian D, Wu JHY. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047-2067.
6. FDA prescribing information for Vascepa (icosapent ethyl) and Lovaza (omega-3-acid ethyl esters).
Note: This information is for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider before starting any new supplement regimen.