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The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia
Open accessAbstract
Hypertriglyceridemia (triglycerides > 150 mg/dL) affects ~25 % of the United States (US) population and is associated with increased cardiovascular risk. Severe hypertriglyceridemia (≥ 500 mg/dL) is also a risk factor for pancreatitis. Three omega-3 fatty acid (OM3FA) prescription formulations are approved in the US for the treatment of adults with severe hypertriglyceridemia: (1) OM3FA ethyl esters (OM3EE), a mixture of OM3FA ethyl esters, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Lovaza®, Omtryg™, and generics); (2) icosapent ethyl (IPE), EPA ethyl esters (Vascepa®); and (3) omega-3 carboxylic acids (OM3CA), a mixture of OM3FAs in free fatty acid form, primarily EPA, DHA, and docosapentaenoic acid (Epanova®). At approved doses, all formulations substantially reduce triglyceride and very-low-density lipoprotein levels. DHA-containing formulations may also increase low-density lipoprotein cholesterol. However, this is not accompanied by increased non-high-density lipoprotein cholesterol, which is thought to provide a better indication of cardiovascular risk in this patient population. Proposed mechanisms of action of OM3FAs include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation. OM3CA bioavailability (area under the plasma concentration-time curve from zero to the last measurable concentration) is up to 4-fold greater than that of OM3FA ethyl esters, and unlike ethyl esters, the absorption of OM3CA is not dependent on pancreatic lipase hydrolysis. All three formulations are well tolerated (the most common adverse events are gastrointestinal) and demonstrate a lack of drug-drug interactions with other lipid-lowering drugs, such as statins and fibrates. OM3FAs appear to be an effective treatment option for patients with severe hypertriglyceridemia.
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![Fig. 2 TG reduction observed with varying doses of omega-3 carboxylic acids, omega-3 ethyl esters, and icosapent ethyl in (a) patients with severe hypertriglyceridemia (TG ≥ 500 mg/dL) [14, 16, 17] and (b) statin-treated patients with high baseline TG levels (TG level ≥ 200 mg/dL and < 500 mg/dL) [20, 21, 24] Data not available for OM3EE at 2 g/day. OM3CA = Percentage change from baseline expressed as least-squares geometric mean; OM3EE = percentage change from baseline expressed as geometric mean; IPE = percentage change from baseline expressed as median. †Placebo used = olive oil; ‡Placebo used = vegetable oil; §Placebo used = mineral oil; ǁPlacebo used = corn oil; ¶Placebo not specified. IPE icosapent ethyl, OM3CA omega-3 carboxylic acids, OM3EE omega-3 ethyl esters, TG triglyceride](/paper-figures/d233ddfca28e42378bc78600998e583a/the-clinical-relevance-of-omega-3-fatty-acids-in-the-management-of-figure-2.jpg)
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“Combined EPA + DHA formulations, such as omega-3 carboxylic acids and ethyl esters, effectively lower TG levels by reducing hepatic VLDL synthesis and enhancing fatty acid oxidation [87].”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [87]
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Standards of medical care in diabetes—2014
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Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease
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Gioxari, A., Kaliora, A. C., Marantidou, F., & Panagiotakos, D. P. (2017) · Nutrition · doi:10.1016/j.nut.2017.06.023 · Cited by 203
Schunck, W., Konkel, A., Fischer, R., & Weylandt, K. H. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.10.016 · Cited by 211
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Metadata
- Authors
- Backes, J., Anzalone, D., Hilleman, D., & Catini, J.
- Affiliations
- University of Kansas (US)
- AstraZeneca (United States) (US)
- Creighton University (US)
- Corresponding author
- Backes, James
- Venue
- Lipids in Health and Disease
- Published
- 2016-07-22
- Volume
- 15
- Issue
- 1
- Pages
- 118-118
- ISSN
- 1476-511X (ISSN-L)
- PMC
- PMC4957330
- OpenAlex
- W2487890137
- Cited by
- 195
- References
- 97
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 20 · 2023: 20 · 2022: 26 · 2021: 29 · 2020: 25 · 2019: 15 · 2018: 9 · 2017: 20 · 2016: 1
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Lipids in Health and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Creighton Digital Repository (CDR) (submittedVersion)
- KU ScholarWorks (The University of Kansas) (submittedVersion, cc-by)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- omega-3 fatty acids, severe hypertriglyceridemia, triglyceride-lowering therapy, icosapent ethyl, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, VLDL, non-HDL cholesterol, lipoprotein lipase, hepatic lipogenesis, fatty acid beta-oxidation, bioavailability, drug-drug interactions, cardiovascular risk, pancreatitis
- MeSH terms
- Adult, Hypolipidemic Agents, Biological Availability, Docosahexaenoic Acids, Drug Combinations, Esters, Humans, Lipoprotein Lipase, Cholesterol, LDL, Lipoproteins, VLDL, Liver, Oxidation-Reduction, Triglycerides, Eicosapentaenoic Acid, Hypertriglyceridemia, Fatty Acids, Omega-3, Lipogenesis, Diacylglycerol O-Acyltransferase
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