Krill Oil - Drug Monograph

Krill Oil - Drug Monograph

Introduction

Krill oil is a dietary supplement derived from Antarctic krill (Euphausia superba), small crustaceans rich in omega-3 fatty acids (primarily eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) bound to phospholipids, along with the antioxidant astaxanthin. Unlike fish oil, krill oil's phospholipid structure may enhance bioavailability and reduce gastrointestinal side effects. It is widely used for cardiovascular health, lipid management, and inflammatory conditions, though regulatory status varies globally.

Mechanism of Action

Krill oil exerts its effects through multiple mechanisms:

• Omega-3 Fatty Acids (EPA/DHA): Incorporated into cell membranes, modulating membrane fluidity and inflammatory signaling. EPA and DHA compete with arachidonic acid for metabolism by cyclooxygenase and lipoxygenase enzymes, reducing production of pro-inflammatory eicosanoids (e.g., prostaglandin E2, leukotriene B4) and increasing anti-inflammatory resolvins and protectins.
• Phospholipid-Bound EPA/DHA: Enhanced bioavailability compared to triglyceride-bound forms in fish oil, facilitating efficient cellular uptake.
• Astaxanthin: A potent carotenoid antioxidant that scavenges free radicals and reduces oxidative stress.
• Lipid Effects: Reduces hepatic very-low-density lipoprotein (VLDL) synthesis and enhances triglyceride clearance via lipoprotein lipase. May modestly increase high-density lipoprotein (HDL) cholesterol.

Indications

• Hypertriglyceridemia (as adjunct therapy; typical reduction of 10-30%)
• Cardiovascular risk reduction (may improve endothelial function, reduce inflammation)
• Rheumatoid arthritis (symptomatic improvement in some studies)
• Premenstrual syndrome and dysmenorrhea
• Mild cognitive support (limited evidence)

Dosage and Administration

• Standard Dose: 1-3 g daily, typically providing 100-300 mg of combined EPA/DHA.
• Administration: Oral capsules, with or without food (though taking with meals may enhance absorption).
• Special Populations:

- Pediatrics: Not established; use only under professional guidance. - Geriatrics: No dose adjustment needed. - Hepatic/Renal Impairment: No specific recommendations; use with caution in severe impairment.

• Duration: Long-term use is common; effects on lipids may be seen within 4-12 weeks.

Pharmacokinetics

• Absorption: EPA/DHA in phospholipid form has higher bioavailability than triglyceride-bound forms in fish oil. Peak plasma concentrations occur within 4-8 hours.
• Distribution: Incorporated into phospholipid membranes of cells, including erythrocytes, platelets, and neuronal tissues. Crosses the blood-brain barrier.
• Metabolism: Metabolized via peroxisomal β-oxidation and cytochrome P450 (CYP4F3B) to bioactive metabolites (e.g., resolvins).
• Elimination: Half-life of EPA/DHA is approximately 48-72 hours. Excreted primarily as carbon dioxide via respiration and in feces.

Contraindications

• Hypersensitivity to krill, crustaceans, or any component of the formulation.
• Known fish or shellfish allergy (due to cross-reactivity risk).
• Use in patients with bleeding disorders or on anticoagulant therapy without medical supervision (relative contraindication).

Warnings and Precautions

• Bleeding Risk: May inhibit platelet aggregation and prolong bleeding time; use cautiously with anticoagulants (e.g., warfarin, apixaban) or antiplatelets (e.g., aspirin, clopidogrel).
• Diabetes: May increase fasting blood glucose in some patients; monitor glycemic control.
• Hyperlipidemia: Paradoxical increases in low-density lipoprotein (LDL) cholesterol have been reported in some individuals.
• Surgery: Discontinue at least 2 weeks prior to elective surgery due to bleeding risk.
• Pregnancy/Lactation: Generally recognized as safe in food amounts; high-dose supplements should be used only under medical supervision.

Drug Interactions

• Anticoagulants/Antiplatelets (e.g., warfarin, heparin, DOACs, aspirin): Increased risk of bleeding; monitor INR and bleeding signs.
• Orlistat: May reduce absorption of fat-soluble components.
• Cytochrome P450 Substrates: Theoretical potential for interaction due to astaxanthin; clinical significance unknown.
• Other Omega-3 Supplements: Additive effects; avoid concomitant use without dose adjustment.

Adverse Effects

• Common (≥1%):

- Gastrointestinal (nausea, diarrhea, dyspepsia, fishy aftertaste—less common than with fish oil) - Headache - Mild increase in LDL cholesterol (in some patients)

• Serious (Rare):

- Allergic reactions (urticaria, angioedema, anaphylaxis in shellfish-allergic patients) - Clinically significant bleeding (e.g., epistaxis, hematuria) - Pancreatitis (theoretical, with very high doses)

Monitoring Parameters

• Baseline: Lipid panel (total cholesterol, LDL, HDL, triglycerides), liver function tests, hemoglobin A1c (if diabetic), bleeding time/INR if on anticoagulants.
• Ongoing:

- Lipid panel after 8-12 weeks of therapy. - Glycemic control in diabetics. - Signs of bleeding (bruising, petechiae) in those on anticoagulants. - Allergy symptoms in susceptible individuals.

Patient Education

• Inform healthcare providers of all supplements taken, especially before surgery or if prescribed anticoagulants.
• Take with meals to improve absorption and reduce GI upset.
• Discontinue and seek medical attention if signs of allergy (rash, swelling, difficulty breathing) or bleeding (unusual bruising, blood in stool) occur.
• Do not exceed recommended doses; high doses may increase side effects without additional benefits.
• Store in a cool, dry place away from light to prevent oxidation.
• Krill oil is not a substitute for prescribed lipid-lowering therapy or a balanced diet.

References

1. Ulven SM, Holven KB. Comparison of bioavailability of krill oil versus fish oil and health effect. Vasc Health Risk Manag. 2015;11:511-524. 2. Bunea R, El Farrah K, Deutsch L. Evaluation of the effects of Neptune krill oil on the clinical course of hyperlipidemia. Altern Med Rev. 2004;9(4):420-428. 3. Köhler A, Sarkkinen E, Tapola N, Niskanen T, Bruheim I. Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects–a randomized, single-dose, cross-over trial. Lipids Health Dis. 2015;14:19. 4. Cicero AF, Rosticci M, Morbini M, et al. Lipid-lowering and anti-inflammatory effects of omega 3 ethyl esters and krill oil: a randomized, cross-over, clinical trial. Arch Med Sci. 2016;12(3):507-512. 5. FDA: Dietary Supplements. Accessed at: www.fda.gov/food/dietary-supplements. 6. National Institutes of Health Office of Dietary Supplements. Omega-3 Fatty Acids Fact Sheet for Health Professionals. Updated 2022.