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Cited by 72Fatty Acid Research and HealthAntioxidant Activity and Oxidative StressLipoproteins and Cardiovascular Health

Eicosapentaenoic acid inhibits oxidation of ApoB-containing lipoprotein particles of different size in vitro when administered alone or in combination with Atorvastatin active metabolite compared with other triglyceride-lowering agents

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Mason, R. Preston, Sherratt, Samuel C.R., Jacob, Robert F.·2016·Journal of Cardiovascular Pharmacology
DOI 10.1097/fjc.0000000000000379PMC PMC4936437
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Abstract

Eicosapentaenoic acid (EPA) is a triglyceride-lowering agent that reduces circulating levels of the apolipoprotein B (apoB)-containing lipoprotein particles small dense low-density lipoprotein (sdLDL), very–low-density lipoprotein (VLDL), and oxidized low-density lipoprotein (LDL). These benefits may result from the direct antioxidant effects of EPA. To investigate this potential mechanism, these particles were isolated from human plasma, preincubated with EPA in the absence or presence of atorvastatin (active) metabolite, and subjected to copper-initiated oxidation. Lipid oxidation was measured as a function of thiobarbituric acid reactive substances formation. EPA inhibited sdLDL (IC 50 ∼2.0 μM) and LDL oxidation (IC 50 ∼2.5 μM) in a dose-dependent manner. Greater antioxidant potency was observed for EPA in VLDL. EPA inhibition was enhanced when combined with atorvastatin metabolite at low equimolar concentrations. Other triglyceride-lowering agents (fenofibrate, niacin, and gemfibrozil) and vitamin E did not significantly affect sdLDL, LDL, or VLDL oxidation compared with vehicle-treated controls. Docosahexaenoic acid was also found to inhibit oxidation in these particles but over a shorter time period than EPA. These data support recent clinical findings and suggest that EPA has direct antioxidant benefits in various apoB-containing subfractions that are more pronounced than those of other triglyceride-lowering agents and docosahexaenoic acid.

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  • A broad literature examining effects of EPA vs EPA/DHA at molecular, cellular, imaging, and clinical endpoint levels suggests more robust benefit with purified EPA rather than mixed EPA/DHA.

    “a broad literature examining effects of EPA vs EPA/DHA at the molecular and cellular levels,39, 40, 41, 42 their effects at the level of atherosclerotic plaque quantifiable with clinical imaging,8 and their effects at the clinical endpoint level evidenced in the RCT literature reviewed here, all suggest more robust benefit with purified EPA rather than mixed EPA/DHA.”

    From Effects of Eicosapentaenoic Acid vs Eicosapentaenoic/Docosahexaenoic Acids on Cardiovascular Mortality (2025) · cites this paper as [40]

    The Results section (page unavailable) reports that EPA inhibited oxidation of human lipoprotein particles more consistently than DHA in vitro, supporting the molecular-level comparison. The study tested EPA and DHA separately, not purified EPA against a mixed EPA/DHA product; its imaging and clinical findings are discussed from other studies rather than tested here. (LLM, conf=0.86)

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Authors
Mason, R. P., Sherratt, S. C. R., & Jacob, R. F.
Affiliations
  • Brigham and Women's Hospital (US)
  • Elucida Research LLC, Beverly, MA.
Corresponding author
Mason, R. Preston
ORCID
Venue
Journal of Cardiovascular Pharmacology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-07
Volume
68
Issue
1
Pages
33-40
ISSN
0160-2446 (ISSN-L)
DOI
10.1097/fjc.0000000000000379
PMC
PMC4936437
OpenAlex
W2290053204
Cited by
72
References
10
Citations by year
2026: 6 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 11 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 1
FWCI
6.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cardiovascular Pharmacology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • Pfizer
  • Amarin Corporation
  • Amarin Pharma
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
eicosapentaenoic acid, apolipoprotein B-containing lipoproteins, small dense LDL, VLDL, LDL oxidation, antioxidant activity, triglyceride-lowering agents, fenofibrate, nicotinic acid, gemfibrozil, vitamin E, docosahexaenoic acid, omega-3 fatty acids
MeSH terms
Atorvastatin, Antioxidants, Dose-Response Relationship, Drug, Drug Therapy, Combination, Humans, Lipoproteins, LDL, Lipoproteins, VLDL, Oxidation-Reduction, Particle Size, Time Factors, Triglycerides, Eicosapentaenoic Acid, Down-Regulation, Thiobarbituric Acid Reactive Substances, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Apolipoprotein B-100

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