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Cited by 92Fatty Acid Research and HealthLipid Membrane Structure and BehaviorLipid metabolism and biosynthesis

EPA and DHA containing phospholipids have contrasting effects on membrane structure

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Sherratt, Samuel C.R., Juliano, Rebecca A., Copland, Christina, Bhatt, Deepak L., Libby, Peter, Mason, R. Preston·2021·Journal of Lipid Research
DOI 10.1016/j.jlr.2021.100106PMC PMC8430377
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Abstract

Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl—Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl- sn -glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl- sn -glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å 3 vs. Å) were used to determine membrane structure, including membrane width ( d -space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0–10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d -space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs.

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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 [39]

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References 72 · Cited by 92

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Authors
Sherratt, S. C. R., Juliano, R. A., Copland, C., Bhatt, D. L., Libby, P., & Mason, R. P.
Affiliations
  • University of New Hampshire (US)
  • Amarin (United States) (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Mason, R. Preston
ORCID
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2021
Volume
62
Pages
100106
ISSN
0022-2275 (ISSN-L)
DOI
10.1016/j.jlr.2021.100106
PMC
PMC8430377
OpenAlex
W3192792201
Cited by
92
References
72
Citations by year
2026: 16 · 2025: 28 · 2024: 20 · 2023: 15 · 2022: 12 · 2021: 1
FWCI
7.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Amarin Pharma Inc
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, omega-3 fatty acids, phospholipids, membrane structure, membrane fluidity, lipid rafts, POPC, cholesterol, icosapent ethyl, cardiovascular events, small-angle X-ray diffraction, electron density profile
MeSH terms
Cell Membrane, Docosahexaenoic Acids, Phospholipids, X-Ray Diffraction, Eicosapentaenoic Acid, Scattering, Small Angle

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