Fish oil and triglycerides are closely linked in cardiovascular health management. Omega-3 fatty acids found in fish oil—particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—have well-established triglyceride-lowering effects through multiple metabolic pathways. Elevated triglyceride levels increase cardiovascular risk and, when very high, can cause acute pancreatitis. Whilst dietary fish intake supports general health, prescription-strength omega-3 preparations are typically required for clinically significant hypertriglyceridaemia. Understanding how fish oil affects triglycerides, appropriate dosing, evidence for its use, and when to seek medical advice helps patients and healthcare professionals make informed decisions about cardiovascular risk reduction.

What Are Triglycerides and Why Do They Matter?

Triglycerides are a type of fat (lipid) found in the blood, formed when the body converts calories it doesn't need immediately into this storage form of energy. After eating, triglycerides are released from the intestines and liver into the bloodstream, where they are transported to tissues for energy use or storage in adipose tissue. In the UK, triglyceride levels below 1.7 mmol/L are generally considered desirable, though optimal levels may be lower.

Elevated triglyceride levels, known as hypertriglyceridaemia, are associated with increased cardiovascular risk. When triglycerides remain persistently elevated—particularly above 2.3 mmol/L—they contribute to the hardening and thickening of arterial walls (atherosclerosis), increasing the risk of heart attack, stroke, and peripheral vascular disease. Very high levels (above 10 mmol/L) also carry a significant risk of acute pancreatitis, a potentially life-threatening inflammatory condition of the pancreas.

Several factors influence triglyceride levels, including dietary intake (particularly refined carbohydrates, sugars, and alcohol), obesity, physical inactivity, type 2 diabetes, metabolic syndrome, and certain medications such as corticosteroids, beta-blockers, and oestrogen-containing preparations. Secondary causes include hypothyroidism, chronic kidney disease, nephrotic syndrome, cholestasis, pregnancy, and uncontrolled diabetes. Genetic conditions, including familial hypertriglyceridaemia, can also cause markedly elevated levels.

NICE guidance (NG238) emphasises that managing triglycerides forms part of comprehensive cardiovascular risk reduction, alongside addressing non-HDL cholesterol levels, blood pressure, smoking cessation, and lifestyle modification.

In the UK, lipid profile testing is typically performed in a non-fasting state and measures total cholesterol, HDL-cholesterol, non-HDL cholesterol, and triglycerides. Identifying and managing elevated triglycerides early can significantly reduce long-term cardiovascular morbidity and mortality, making awareness of this lipid parameter clinically important for both patients and healthcare professionals.

How Fish Oil Affects Triglyceride Levels

Fish oil contains long-chain omega-3 polyunsaturated fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which exert multiple beneficial effects on lipid metabolism. The triglyceride-lowering mechanism of omega-3 fatty acids is well-established and involves several complementary pathways.

The primary mechanism involves reduced hepatic triglyceride synthesis. EPA and DHA decrease the activity of enzymes involved in fatty acid synthesis, particularly by downregulating sterol regulatory element-binding protein-1c (SREBP-1c), a key transcription factor that controls genes responsible for triglyceride production. Additionally, omega-3 fatty acids enhance the activity of lipoprotein lipase in peripheral tissues (endothelium, adipose tissue, and muscle), the enzyme responsible for breaking down triglyceride-rich lipoproteins in the circulation, thereby accelerating triglyceride clearance from the bloodstream.

Omega-3 fatty acids also increase fatty acid oxidation within liver cells, effectively shifting hepatic metabolism away from triglyceride synthesis and towards fat burning. This is achieved through activation of peroxisome proliferator-activated receptors (PPARs), which regulate genes involved in fatty acid oxidation. Furthermore, fish oil supplementation reduces the secretion of very-low-density lipoprotein (VLDL) particles from the liver—the primary carriers of triglycerides in the blood.

The magnitude of triglyceride reduction with fish oil is dose-dependent, with higher doses of EPA and DHA producing more substantial effects. Clinical studies consistently demonstrate reductions of 20–50% in triglyceride levels with prescription-strength omega-3 preparations, though the response varies based on baseline triglyceride levels, with greater absolute reductions observed in individuals with more severe hypertriglyceridaemia. It's important to note that whilst fish oil effectively lowers triglycerides, it may cause modest increases in LDL-cholesterol in some individuals.

Evidence for Fish Oil in Managing High Triglycerides

The evidence base supporting omega-3 fatty acids for triglyceride reduction is robust, spanning several decades of clinical research. Multiple systematic reviews and meta-analyses have consistently demonstrated significant triglyceride-lowering effects.

A landmark meta-analysis published in the Journal of the American Heart Association examined 47 randomised controlled trials and found that omega-3 supplementation reduced triglycerides by an average of 0.34 mmol/L (approximately 15%), with greater reductions observed at higher doses and in individuals with elevated baseline levels. Studies using prescription-strength preparations (containing 2–4 grams of EPA and DHA daily) have demonstrated reductions of up to 45% in patients with severe hypertriglyceridaemia.

In the UK, omega-3-acid ethyl esters are licensed as an adjunct to diet for the treatment of endogenous hypertriglyceridaemia. NICE guidance (NG238) advises against offering omega-3 fatty acid supplements for the primary or secondary prevention of cardiovascular disease in general, with one specific exception.

This exception is icosapent ethyl (Vazkepa), which is recommended by NICE (TA805) for reducing cardiovascular risk in adults with elevated triglycerides (1.7–5.6 mmol/L) who meet specific criteria: established cardiovascular disease, controlled LDL-cholesterol on statins, and other risk factors. This recommendation is based on the REDUCE-IT trial, published in the New England Journal of Medicine, which demonstrated that high-dose purified EPA (icosapent ethyl 4 grams daily) significantly reduced cardiovascular events in this specific patient group.

The STRENGTH trial, using a different omega-3 formulation (combined EPA and DHA), showed neutral cardiovascular outcomes, highlighting that not all omega-3 preparations may be equivalent.

Whilst over-the-counter fish oil supplements contain omega-3 fatty acids, they typically provide lower concentrations than prescription preparations and lack the rigorous quality control and standardisation of licensed medicines. For clinically significant hypertriglyceridaemia, prescription omega-3 preparations are generally preferred to ensure adequate dosing and pharmaceutical-grade purity.

Recommended Doses and Types of Fish Oil for Triglycerides

The appropriate dose of omega-3 fatty acids depends on the clinical context and whether the preparation is a licensed medicine or a food supplement. For general cardiovascular health, organisations such as the British Heart Foundation suggest consuming two portions of fish weekly (one oily), providing approximately 450 mg of EPA and DHA daily. However, this dietary intake is insufficient for therapeutic triglyceride reduction.

For hypertriglyceridaemia, prescription omega-3 preparations are recommended. In the UK, omega-3-acid ethyl esters (such as Omacor) are licensed as an adjunct to diet for endogenous hypertriglyceridaemia. The usual dose is 2–4 capsules daily (providing 1.8–3.6 g of EPA and DHA ethyl esters), as specified in the Summary of Product Characteristics (SmPC).

Icosapent ethyl (Vazkepa) is licensed and NICE-recommended (TA805) specifically for cardiovascular risk reduction in adults with elevated triglycerides (1.7–5.6 mmol/L) who meet specific criteria. The recommended dose is 2 g twice daily with food, as per the SmPC.

Over-the-counter fish oil supplements vary considerably in omega-3 content—a standard 1000 mg fish oil capsule may contain only 300 mg of combined EPA and DHA. These supplements are not licensed medicines and should not be used as a substitute for prescribed treatment of significant hypertriglyceridaemia. Patients should consult their healthcare professional before using supplements for managing elevated triglycerides.

When selecting fish oil supplements, patients should:

• Check the EPA and DHA content per capsule, not just total fish oil content

• Choose products with third-party testing certification for purity and potency

• Consider concentrated formulations to reduce pill burden

Fish oil should be taken with meals to enhance absorption and reduce gastrointestinal side effects. Patients taking prescription omega-3 preparations should not supplement with additional over-the-counter fish oil without medical guidance, as excessive doses may increase bleeding risk and provide no additional benefit. Regular monitoring of lipid profiles, typically after 3 months of treatment and then annually once stable (as recommended by NICE), helps assess treatment response and guide dose adjustments.

Potential Side Effects and Safety Considerations

Fish oil supplementation is generally well-tolerated, but patients should be aware of potential adverse effects and important safety considerations. The most common side effects are gastrointestinal, including fishy aftertaste, belching, nausea, loose stools, and indigestion. These effects are usually mild and can be minimised by taking fish oil with meals, choosing enteric-coated preparations, or refrigerating capsules. Starting with lower doses and gradually increasing can also improve tolerability.

An important consideration is the potential effect on bleeding risk. Omega-3 fatty acids have mild antiplatelet effects, theoretically increasing bleeding tendency. Whilst clinically significant bleeding is rare at recommended doses, caution is advised in patients taking anticoagulants (warfarin, DOACs), antiplatelet agents (aspirin, clopidogrel), or those with bleeding disorders. Patients on warfarin should have their INR monitored when starting or stopping omega-3 supplements. Individuals on multiple antithrombotic medications should discuss supplementation with their GP or anticoagulation clinic.

High-dose omega-3 fatty acids, particularly icosapent ethyl, have been associated with an increased risk of atrial fibrillation. Patients should seek medical advice if they experience palpitations or symptoms of an irregular heartbeat.

Some patients experience a modest increase in LDL-cholesterol (typically 5–10%) with high-dose fish oil. Patients with combined dyslipidaemia should have lipid profiles monitored after initiating omega-3 therapy. Additionally, fish oil may cause slight elevations in fasting blood glucose in some individuals with diabetes, though this effect is generally small.

Allergic reactions are possible in individuals with fish or shellfish allergies, though highly purified omega-3 preparations typically contain minimal allergenic protein. Patients with documented fish allergy should consult an allergist before using fish oil. Alternative sources of omega-3s, such as algal oil (providing DHA), may be suitable for those with fish allergies or following vegetarian/vegan diets.

Patients planning surgery should discuss omega-3 supplementation with their surgical team, as some clinicians may advise temporarily stopping supplements before procedures, though evidence for this practice is limited.

Suspected adverse reactions to fish oil products, particularly prescription preparations, should be reported through the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).

When to Seek Medical Advice About Triglycerides

Patients should consult their GP or practice nurse if they have risk factors for elevated triglycerides, including obesity (particularly central adiposity), type 2 diabetes, metabolic syndrome, excessive alcohol consumption, or a family history of premature cardiovascular disease or hypertriglyceridaemia. Routine lipid screening is recommended for adults over 40 as part of NHS Health Checks, and earlier for those with additional cardiovascular risk factors.

Urgent medical attention is warranted if symptoms suggestive of acute pancreatitis develop, particularly in individuals with known severe hypertriglyceridaemia. Warning signs include severe, persistent upper abdominal pain (often radiating to the back), nausea, vomiting, and fever. Acute pancreatitis is a medical emergency requiring hospital admission.

Specialist referral should be considered for patients with persistently elevated triglycerides ≥10 mmol/L despite treatment, and urgent specialist advice sought if levels exceed 20 mmol/L or if there are symptoms of pancreatitis.

Patients already taking fish oil supplements should seek medical review if they experience:

• Unusual bleeding or bruising, particularly if taking anticoagulant or antiplatelet medications

• Persistent gastrointestinal symptoms that don't improve with dose adjustment or formulation changes

• Allergic reactions, including rash, itching, swelling, or breathing difficulties

• Palpitations or symptoms of irregular heartbeat, which could indicate atrial fibrillation

• Significant changes in blood glucose control in individuals with diabetes

Before starting fish oil supplementation, patients should discuss this with their GP if they have existing medical conditions (particularly bleeding disorders, liver disease, or diabetes), are taking multiple medications, are pregnant or breastfeeding, or are planning surgery.

Regular monitoring is essential for individuals with diagnosed hypertriglyceridaemia. NICE recommends repeat lipid profiles 3 months after initiating lifestyle changes or lipid-modifying therapy, then annually once stable. Patients with very high triglycerides may require more frequent monitoring.

When evaluating elevated triglycerides, healthcare professionals should consider secondary causes including hypothyroidism, chronic kidney disease, uncontrolled diabetes, excess alcohol consumption, and certain medications. Addressing these underlying factors is often essential for effective management.

Patients should not self-treat significantly elevated triglycerides with over-the-counter supplements alone. Comprehensive cardiovascular risk assessment and management, including addressing all modifiable risk factors, provides the most effective approach to reducing cardiovascular events. Your GP can arrange appropriate investigations, provide personalised advice on lifestyle modification, and determine whether prescription lipid-lowering therapy is indicated based on your overall cardiovascular risk profile.

Frequently Asked Questions