Omega-3 Polyunsaturated Fatty Acids

Introduction Overview

Generic Name

omega-3 polyunsaturated fatty acids

Brand Name

Mercola Krill Oil
Schiff MegaRed Omega-3 Krill Oil
Neptune Krill Oil
Red Whale Krill Oil

Dosage Form

Oral capsule (softgel)

Drug Class

Dietary supplement - Omega-3 fatty acid supplement

Pharmacokinetics

Absorption:
Krill Oil's omega-3 fatty acids, primarily EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), are absorbed via the gastrointestinal tract when ingested orally. Unlike conventional fish oil where omega-3s are mainly present in the form of triglycerides, the omega-3 fatty acids in Krill Oil are primarily bound to phospholipids, which facilitates enhanced bioavailability and membrane integration. Studies indicate superior incorporation of EPA and DHA into plasma phospholipids after Krill Oil consumption compared to fish oil, attributed to this phospholipid form. Absorption occurs primarily in the small intestine, with bile salts facilitating emulsification, and pancreatic lipases hydrolyzing the lipids for transport.

Distribution:
Following absorption, the phospholipid-bound EPA and DHA are efficiently transported via chylomicrons through the lymphatic system into systemic circulation. Because these omega-3s are incorporated into phospholipids, they show better uptake into cell membranes, including erythrocytes, hepatocytes, and cardiac and neural tissue, compared to triglyceride-based fish oils. This selective distribution impacts various tissues involved in inflammatory processes, lipid metabolism, and cardiovascular function. Krill Oil also contains astaxanthin, a potent carotenoid antioxidant, which may contribute to distribution dynamics by protecting lipids against oxidative degradation.

Metabolism:
The omega-3 fatty acids from Krill Oil are metabolized in the liver via enzymatic pathways, including elongation and desaturation reactions for DHA and EPA. Through beta-oxidation, some EPA and DHA are metabolized for energy production, whereas others are incorporated into membrane phospholipids or serve as precursors for bioactive lipid mediators such as resolvins and protectins, which have roles in resolving inflammation. The presence of astaxanthin may reduce oxidative stress during the metabolism process. Krill Oil's phosphatidylcholine component may also influence lipid metabolism pathways by modulating membrane composition and function.

Elimination:
Metabolic by-products of omega-3 fatty acids are predominantly eliminated via renal and fecal routes. Smaller amounts may be lost as expired carbon dioxide after complete oxidation. The relatively long half-life of incorporated omega-3 phospholipids in cell membranes contributes to sustained biological effects following ingestion. Clinical studies suggest that EPA and DHA levels remain elevated in plasma phospholipids for several days post-dose, reflecting slower elimination when bound to phospholipids. There is limited data on the direct elimination kinetics of astaxanthin in humans from Krill Oil, but it is expected to follow similar pathways involving hepatic metabolism and biliary/fecal excretion.

Dosage Forms

Available Dosage Forms:
Krill Oil is commercially available predominantly in oral softgel capsules form. These capsules contain varying amounts of omega-3 fatty acids, mainly EPA and DHA, alongside phospholipids and astaxanthin. The doses per capsule can vary by manufacturer, commonly ranging from 300 mg to 1,000 mg total Krill Oil content per capsule. Examples of marketed products include Mercola Krill Oil and Neptune Krill Oil.

Dosages for Adults and Adolescents:
Typical adult dosing ranges from 300 mg to 1,000 mg of Krill Oil daily, usually administered orally in one or two divided doses. Some clinical studies employed doses of 300 mg to 1,000 mg per day for lipid lowering and anti-inflammatory effects. Optimal dosing depends on the specific therapeutic goal, such as triglyceride reduction or symptom relief in osteoarthritis or PMS. Currently, there are no established dosing guidelines for adolescents; use in individuals under 18 years is generally not recommended due to limited safety data.

Specific Patient Populations:
Use in pregnancy and lactation is not well established; therefore, Krill Oil should be used with caution in pregnant or breastfeeding women, and only under physician supervision. Patients with seafood allergies, particularly to fish or shellfish such as shrimp or Krill, should avoid Krill Oil due to risk of allergic reactions. Patients with bleeding disorders or those on anticoagulant therapies should consult healthcare providers before use because of potential additive effects on bleeding risk. Renal or hepatic impairment impact on Krill Oil pharmacokinetics has not been comprehensively studied but caution and medical advice are warranted.

Krill Oil capsules should be swallowed whole and not punctured or opened. It is recommended to take with food to enhance absorption and minimize gastrointestinal upset. Storage is at room temperature, away from moisture and heat, and freezing is not advised.

Mechanism Of Action

Krill Oil exerts its pharmacologic effects primarily through its omega-3 polyunsaturated fatty acid components, EPA and DHA, which are crucial substrates for modulation of lipid metabolism and inflammatory pathways. The unique composition of EPA and DHA bound to phospholipids in Krill Oil facilitates enhanced absorption and incorporation into cell membranes, thereby influencing membrane fluidity and cellular signaling.

At the molecular level, EPA and DHA serve as precursors for the synthesis of eicosanoids and specialized pro-resolving mediators (SPMs), including resolvins and protectins, which have potent anti-inflammatory and immunomodulatory properties. By competing with arachidonic acid substrates, these omega-3 fatty acids reduce the production of pro-inflammatory prostaglandins and leukotrienes, thus attenuating inflammatory responses correlated with chronic diseases such as atherosclerosis and arthritis.

Additionally, Krill Oil's phospholipids, mainly phosphatidylcholine, contribute to cellular membrane structure and function, facilitating efficient delivery of omega-3 fatty acids to tissues. Phosphatidylcholine also has roles in lipid transport and metabolism, which may impact plasma lipid profiles, including reductions in triglycerides and low-density lipoprotein (LDL) cholesterol, and increases in high-density lipoprotein (HDL) cholesterol.

Krill Oil contains the antioxidant carotenoid astaxanthin, which scavenges reactive oxygen species and prevents oxidative damage to lipids, proteins, and nucleic acids. This antioxidant effect may protect omega-3 fatty acids from peroxidation, prolong their biological activity, and contribute to the overall cardioprotective and anti-inflammatory actions observed.

Clinical implications of these mechanisms include reduced risk of coronary artery disease through lipid profile improvement and inflammation reduction, potential amelioration of arthritic symptoms via decreased joint inflammation, and possible benefits in neurological and mood disorders linked to neuroinflammation. Comparative studies highlight that Krill Oil may achieve similar or superior therapeutic effects compared to fish oil at lower doses, attributed to its phospholipid-bound delivery and antioxidant content, although further high-quality clinical trials are warranted to confirm these advantages comprehensively.

Pharmacological Actions

Provides omega-3 fatty acids EPA and DHA in phospholipid form, enhancing bioavailability.
Lowers triglyceride levels and modulates lipid profile by decreasing LDL and potentially increasing HDL cholesterol.
Exerts anti-inflammatory effects via decreased production of pro-inflammatory eicosanoids and increased synthesis of pro-resolving mediators.
Antioxidant activity through astaxanthin content, protecting lipids and cellular components from oxidative damage.
Modulates cell membrane fluidity and function by incorporation of phospholipids with omega-3 fatty acids.
Potential neuroprotective effects related to modulation of neuroinflammation and membrane composition.
Possible anticoagulant effects that may influence blood clotting parameters.
May reduce symptoms related to osteoarthritis, premenstrual syndrome, and depression by modulating inflammatory pathways and neurotransmitter function.
Supports cardiovascular health by reducing risk factors associated with coronary artery disease.
Contributes to overall lipid metabolism regulation and may improve metabolic syndrome components.

Therapeutic Or Clinical Uses

Supplementation to lower elevated triglycerides and manage dyslipidemia.
Adjunct therapy to reduce risk factors of coronary artery disease and cardiovascular events.
Management of chronic inflammation-related conditions such as osteoarthritis.
Supportive treatment for premenstrual syndrome (PMS) symptoms management.
Adjunctive use in depressive disorders due to omega-3 effects on neuronal function.
Potential complementary therapy for high blood pressure management, although evidence is limited.
Possible supportive role in stroke recovery and prevention.
Exploratory use in malignancy-related symptom management, though evidence is preliminary.
Dietary supplementation for individuals with inadequate omega-3 intake from diet.
Potential use in metabolic syndrome and associated insulin resistance.
Support to improve cognitive function and neuroprotection in age-related decline.
Adjunctive therapy in inflammatory and immune-mediated disorders.
Use in weight management programs as part of comprehensive lifestyle interventions.
Alternative to fish oil supplements for patients intolerant to fish oil due to lower fishy aftertaste.
General antioxidant support to counteract oxidative stress.

Side Or Adverse Effects

Allergic reactions including hives, swelling, difficulty breathing, especially in patients with seafood allergies.
Mild gastrointestinal discomfort such as abdominal pain or indigestion.
Fishy aftertaste or belching experienced by some patients.
Mild skin rash reported rarely.
Potential increased bleeding risk, particularly in patients on anticoagulant or antiplatelet medications.
Rare flu-like symptoms including fever, chills, or body aches in hypersensitive individuals.
Chest pain or palpitations noted rarely, requiring prompt medical evaluation.
Uneven heartbeats or arrhythmias reported in isolated cases.
Possible interaction-related side effects when taken concomitantly with blood thinners or NSAIDs.
Headache or dizziness in a minority of users.
Fatigue or malaise reported sporadically.
Nausea or dyspepsia, especially if taken on an empty stomach.
Potential for contamination-related adverse effects due to environmental toxins accumulation in krill, though generally low.
Overdose may cause bleeding complications or allergic reactions.
No significant serious adverse events reported in controlled studies when used within recommended dosing.

Precautions

Avoid Krill Oil use in individuals with known allergies to fish, shrimp, or other seafood due to risk of severe allergic reactions.
Consult a healthcare provider before use if patient has diabetes, liver disease, pancreas disorders, or bleeding/clotting abnormalities.
Patients scheduled for surgery should discontinue Krill Oil at least two weeks prior to reduce bleeding risk.
Use cautiously in patients on anticoagulants, antiplatelet agents, NSAIDs, or other medications affecting coagulation.
Pregnant or breastfeeding women should consult their physician before using Krill Oil due to insufficient safety data.
Not recommended for children under 18 years old due to lack of established safety and efficacy.
Patients consuming excessive alcohol should exercise caution, as alcohol may exacerbate lipid disorders and interfere with the supplement's efficacy.
Monitor lipid profiles and coagulation parameters as clinically indicated during prolonged use.
Use with caution in patients with hypothyroidism or metabolic syndrome due to uncertain interaction profiles.
Discontinue use and seek medical advice if signs of allergic reaction or unexpected adverse effects occur.
Store at room temperature away from moisture and heat to maintain product stability.
Counsel patients to adhere to prescribed dosing and not exceed recommended amounts.
Advise patients that Krill Oil is a supplement and should be used in conjunction with dietary and lifestyle modifications.
Avoid use in patients with fish oil intolerance unless under medical supervision.
Patients should inform their healthcare providers of all supplements and medications being taken to avoid interactions.

Warnings

Do not exceed recommended doses to avoid increased risk of bleeding or allergic reactions.
Discontinue use at least two weeks before surgery or invasive procedures to reduce bleeding risk.
Avoid use in patients with known hypersensitivity to seafood, including fish and crustaceans.
Use with caution in patients taking anticoagulant or antiplatelet therapies due to additive bleeding risk.
Monitor for signs of serious allergic reactions such as angioedema, anaphylaxis, respiratory distress, or severe rash.
Krill Oil is not FDA-approved to diagnose, treat, or prevent any disease; used as a dietary supplement.
Potential contamination with environmental toxins, such as organic pesticides or methylmercury, though generally lower than in fish oils.
Patients should inform healthcare providers about Krill Oil use prior to starting new medications due to potential drug interactions.
Fishy reflux, belching, or gastrointestinal discomfort may occur; seek medical advice if symptoms persist.
Avoid substituting Krill Oil for prescribed medications without physician guidance.
Not intended for use in children or adolescents without medical consultation.
Pregnant and lactating women should weigh risks versus benefits and consult a healthcare professional before use.
Ensure product quality and source reputable manufacturers to minimize risk of contamination.
Do not puncture or open capsules to avoid degradation or exposure to allergens.
Krill Oil supplements should be part of a comprehensive treatment plan including diet and exercise.

Contraindication

Known allergy or hypersensitivity to fish, shrimp, or any seafood products.
Active bleeding disorders or coagulopathies without appropriate medical supervision.
Concurrent use with anticoagulants or antiplatelet drugs without physician approval.
Hypersensitivity to any components or excipients of the Krill Oil supplement.
Pediatric patients under 18 years of age due to insufficient safety data.
Pregnancy and lactation if not specifically recommended by a healthcare provider.
History of severe allergic reactions to related omega-3 fatty acid products or marine-derived supplements.
Severe hepatic or renal impairment may be a relative contraindication pending clinical judgment.
Intolerance to softgel capsule excipients leading to adverse response.
Uncontrolled bleeding conditions or recent major surgery until cleared by a physician.
Use with caution or contraindicated if patient has history of asthma or atopy related to fish or shellfish allergens.
Avoid use if the product is expired, altered, or improperly stored.
Take precautions if patient has lipid metabolism disorders without medical supervision.
Contraindicated in individuals with known sensitivity to astaxanthin or phospholipid components.
Not recommended as sole therapy for cardiovascular or inflammatory diseases.

Drug Interactions

May potentiate the effects of anticoagulants such as warfarin, increasing bleeding risk.
Concurrent use with antiplatelet agents like aspirin or NSAIDs may enhance bleeding tendency.
Interactions with beta-blockers (atenolol, metoprolol, propranolol, carvedilol) have been reported; monitor blood pressure and heart rate closely.
Diuretics such as hydrochlorothiazide or chlorothiazide may interact by altering electrolyte balance affecting lipid metabolism.
Orlistat may reduce the absorption of fat-soluble components of Krill Oil; monitor efficacy.
Caution with concomitant use of estrogens (birth control or hormone replacement therapy) due to potential modulation of lipid profile.
Potential pharmacodynamic interactions with antihypertensive medications warrant monitoring.
May affect the metabolism of other lipid-lowering agents; clinical significance unclear but warrants caution.
Co-administration with drugs metabolized by hepatic enzymes could theoretically alter metabolism; data limited.
No significant interactions reported with common dietary supplements, but polypharmacy requires careful evaluation.
May interact with immunosuppressant drugs through immune modulation pathways.
Avoid initiating new medications without informing healthcare provider when taking Krill Oil due to possible interactions.
Potential additive hypolipidemic effects when combined with niacin or fibrates.
Excessive combined use with multiple omega-3 supplements may lead to overdose-related adverse events.
Monitoring required when used alongside anticoagulants, antidiabetics, or antihypertensive agents.

Preparations Of The Drug

Mercola Krill Oil – softgel capsules providing standardized omega-3 phospholipids and astaxanthin.
Schiff MegaRed Omega-3 Krill Oil – marketed for cardiovascular and joint health, available in capsule form.
Neptune Krill Oil – one of the widely studied krill oil preparations with clinical data supporting lipid-lowering effects.
Red Whale Krill Oil – alternative brand with comparable composition of EPA, DHA, and phospholipids.
Various formulations containing 300 mg to 1,000 mg total Krill Oil per softgel capsule, standardized to omega-3 content.
Products typically include natural carotenoid antioxidant astaxanthin for enhanced oxidative stability.
Available as over-the-counter dietary supplements without prescription requirement.
Manufactured under Good Manufacturing Practice (GMP) to ensure purity and potency.
Formulations may include additional excipients like gelatin, glycerin, and water to create softgel capsules.
Some preparations combine Krill Oil with other supplements such as vitamins or antioxidants.
Packaging often includes blister packs or bottles designed to protect capsules from moisture and light.
Storage recommendations emphasize room temperature conditions away from heat and humidity.
Commercial preparations vary in omega-3 concentration and astaxanthin levels; consumers should refer to labels.
Purity testing for environmental contaminants like heavy metals and pesticides is conducted by reputable manufacturers.
Krill Oil supplements formulated for adult use; pediatric use formulations are generally unavailable.