What effect do omega-3 fatty acids have on lipids?

Effects of Omega-3 Fatty Acids on Lipids

Omega-3 fatty acids significantly reduce plasma triglyceride levels by 25-30% at higher doses (4g/day), with accompanying modest increases of 5-10% in LDL-C and 1-3% in HDL-C. 1

Primary Lipid Effects

• Omega-3 fatty acids produce a substantial dose-dependent reduction in serum triglycerides, with greater effects observed in individuals with higher baseline triglyceride levels 1, 2
• Marine-derived omega-3 fatty acids (EPA and DHA) are effective for triglyceride lowering, while plant-based omega-3 fatty acids (α-linolenic acid) have not demonstrated consistent reductions in triglycerides 1
• The triglyceride-lowering effect shows a nearly linear dose-response relationship, particularly at medium to high doses (>2 g/day) 2
• Higher doses (4g/day) of omega-3 fatty acids can decrease serum triglyceride concentrations by 25-30% 1

Mechanisms of Action

• Omega-3 fatty acids reduce plasma triglyceride levels through decreased VLDL triglyceride secretion from the liver 1, 3
• They reduce hepatic lipogenesis (fat production in the liver) and increase mitochondrial and peroxisomal β-oxidation, decreasing the synthesis of triglycerides 3, 4
• Omega-3 fatty acids increase plasma lipoprotein lipase activity, which facilitates VLDL triglyceride clearance 1, 3
• EPA and DHA are poor substrates for the enzymes responsible for triglyceride synthesis and inhibit esterification of other fatty acids 3
• Biliary C22:6 omega-3 fatty acid–derived N-acyl taurines prevent intestinal triglyceride absorption, providing an additional mechanism for how DHA lowers plasma and liver triglyceride levels 5

Effects on Other Lipid Parameters

• Omega-3 fatty acids may modestly increase LDL cholesterol by 5-10%, particularly with formulations containing DHA 1, 6
• HDL cholesterol changes are variable and inconsistent, typically showing small increases of 1-3% 1, 7
• Non-HDL cholesterol is reduced in a dose-dependent manner, particularly at higher doses 2
• The effects on LDL cholesterol appear to follow a J-shaped dose-response curve 2
• In longer-term studies (≥4 months) with normo- or slightly hyperlipidemic individuals, changes in LDL cholesterol were not significantly different from placebo 8

Dosing Considerations

• The American Heart Association recommends 2-4g of EPA plus DHA per day, under physician supervision, for patients who need to lower their triglyceride levels 1
• The smallest amount of omega-3 LC-PUFA needed to significantly lower serum triglycerides appears to be approximately 1 g/day as provided by a fish diet 8
• Significant triglyceride reduction has been observed with as little as 0.21g EPA and 0.12g DHA per day in hyperlipidemics 8
• The triglyceride-lowering effect is dose-dependent, with greater reductions seen at higher doses 1, 2

Clinical Considerations and Cautions

• High-dose omega-3 fatty acid supplementation (>1g/day) has been associated with a 25% increase in the risk for atrial fibrillation in clinical trials 1, 5
• EPA and DHA may have differential effects on lipoproteins, with DHA-containing products more likely to raise LDL-C 6
• The triglyceride-lowering effects are more pronounced in populations with hyperlipidemia and overweight/obesity 2
• Omega-3 fatty acids have complementary mechanisms of action with statins, providing additional lipid benefits when administered together 4

Cardiovascular Outcomes

• Meta-analyses of omega-3 fatty acid trials have reported dose-dependent effects with significant reductions in myocardial infarction, coronary heart disease, fatal MI, and mortality 1
• Increasing intake by 1g/day of EPA+DHA corresponded to a 9% lower risk of MI, 7% lower risk of total CHD, and 5.8% lower risk of CVD events 5, 1
• Higher plasma levels of EPA (≥150 µg/dL) have been associated with significant reduction in coronary heart disease event risk 5