Omega-3 Fatty Acids for Dyslipidemia Management
Marine-derived omega-3 fatty acids (EPA and DHA) effectively lower triglyceride levels, with a dose-dependent effect of 5-10% reduction in triglycerides for every 1g of EPA/DHA consumed, making them beneficial for dyslipidemia management. 1
Efficacy for Triglyceride Reduction
- 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
- Higher doses (4g/day) of marine-derived omega-3 fatty acids can decrease serum triglyceride concentrations by 25-30%, with accompanying modest increases of 5-10% in LDL-C and 1-3% in HDL-C 1
- The triglyceride-lowering effect is greater in individuals with higher baseline triglyceride levels before treatment 1
- A recent dose-response meta-analysis demonstrated that combined intake of omega-3 fatty acids nearly linearly lowers triglyceride and non-high-density lipoprotein cholesterol 2
Mechanisms of Action
- Omega-3 fatty acids reduce plasma triglyceride levels through:
- Decreased VLDL triglyceride secretion from the liver 1
- Preferential shunting of omega-3 PUFA into phospholipid cellular synthesis 1
- Reduced expression of SREBP-1 1
- Enhanced peroxisomal β-oxidation 1
- Upregulation of lipoprotein lipase (LPL) which facilitates VLDL triglyceride clearance 1
- Prevention of intestinal triglyceride absorption through biliary C22:6 omega-3 fatty acid-derived N-acyl taurines 1
Source Considerations
- Marine-derived omega-3 fatty acids (EPA and DHA) are effective for triglyceride lowering, while non-marine-based omega-3 fatty acids (α-linolenic acid from plant sources) have not demonstrated consistent reductions in triglycerides 1
- This difference may reflect very low conversion rates of α-linolenic acid to the active triglyceride-lowering omega-3 compounds EPA and DHA 1
- Therefore, if omega-3 PUFAs are used for triglyceride lowering, they should be exclusively marine-derived EPA and/or DHA 1
Formulation Differences
- Prescription omega-3 fatty acids are available in different formulations:
- Omega-3 fatty acid ethyl esters (containing both EPA and DHA ethyl esters) 3
- Icosapent ethyl (IPE; containing high-purity EPA ethyl ester) 3
- Omega-3 formulations containing EPA and DHA have been shown to increase LDL-C levels while IPE has been shown to lower triglyceride levels without raising LDL-C levels 3
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 1
- However, some studies with low-dose mixtures of EPA and DHA have failed to show significant reduction in cardiovascular endpoints, particularly when used with contemporary background therapy including statins 1
Safety Considerations
- 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
- This risk appears to be dose-dependent, with most increased risk occurring in trials testing >1g/day 1
Recommendations for Clinical Practice
- For patients with hypertriglyceridemia:
- Omega-3 fatty acids can be used in conjunction with statins for greater improvements in lipid profiles compared to treatment with statins alone 4, 5
- Instead of supplements, the American Heart Association recommends consuming fatty fish at least two times per week as part of a healthy diet for the general population 6
Practical Considerations
- Dietary sources of EPA and DHA include fatty fish such as anchovy, herring, salmon, and sardines, with varying amounts of omega-3 PUFA per serving 1
- Relying on supplements rather than food sources means missing other beneficial nutrients found in fish 6
- Response to omega-3 fatty acid treatment may be influenced by individual factors such as ApoE genotype 5