EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study
Open accessAbstract
Background and aims The independent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on chronic inflammation through their downstream lipid mediators, including the specialized pro-resolving lipid mediators (SPM), remain unstudied. Therefore, we compared the effects of EPA and DHA supplementation on monocyte inflammatory response and plasma polyunsaturated fatty acids (PUFA) SPM lipidome. Methods After a 4-week lead-in phase (baseline), 9 men and 12 postmenopausal women (50-75 years) with chronic inflammation received two phases of 10-week supplementation with 3 g/day EPA and DHA in a random order, separated by a 10-week washout. Results Compared with baseline, EPA and DHA supplementation differently modulated LPS-stimulated monocyte cytokine expression. EPA lowered TNFA (p Conclusions EPA and DHA had distinct effects on monocyte inflammatory response with a broader effect of DHA in attenuating pro-inflammatory cytokines. These differential effects were potentially mediated by different groups of PUFA derivatives, suggesting immunomodulatory activities of SPM and their intermediates.
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EPA and DHA differ in their biological effects on membrane structure and lipid metabolism.
“since EPA and DHA differ in their biological effects on membrane structure and lipid metabolism”
From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [8]
A significant body of evidence suggests that EPA and DHA markedly differ regarding their effects on membrane structure, inflammatory cascade, lipid oxidation, endothelial function, and tissue distribution.
“a signi fi cant body of evidence suggests that both EPA and DHA markedly differ regarding their effects on membrane structure, in fl ammatory cascade [8], lipid oxidation, endothelial function, and tissue”
From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [8]
Some studies have reported comparable or even greater efficacy of DHA in reducing TGs and individual pro-inflammatory cytokines than EPA.
“Although some studies have reported comparable or even greater ef fi cacy of DHA in reducing TGs and individual pro-in fl ammatory cytokines than EPA [8,25,26]”
From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [8]
Fibrates have shown benefit as monotherapy but not when added to statin therapy.
“Fibrates have shown benefit as monotherapy but not when added to statin therapy, as recently reviewed (28).”
From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [28]
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Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
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Specialized Proresolving Mediators Enhance Human B Cell Differentiation to Antibody-Secreting Cells
Ramon, S., Gao, F., Serhan, C. N., & Phipps, R. P. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103483 · Cited by 145 · see citing works
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Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis
Khan, S. U., Lone, A. N., Khan, M. S., Virani, S. S., Blumenthal, R. S., Nasir, K., Miller, M., Michos, E. D., Ballantyne, C. M., Boden, W. E., et al. (2021) · eClinicalMedicine · doi:10.1016/j.eclinm.2021.100997 · Cited by 411 · see citing works
“Various studies have shed light on the distinct structure, formation, and metabolism of EPA and DHA and their biological effects [1,8,25,26].”
BackgroundResultVirani, S. S., Morris, P. B., Agarwala, A., Ballantyne, C. M., Birtcher, K. K., Kris-Etherton, P. M., Ladden-Stirling, A. B., Miller, M., Orringer, C. E., & Stone, N. J. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.06.011 · Cited by 341 · see citing works
The dawn of a new era of targeted lipid-lowering therapies
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Blood omega-3 fatty acids and death from COVID-19: A pilot study
Asher, A., Tintle, N. L., Myers, M., Lockshon, L., Bacareza, H., & Harris, W. S. (2021) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2021.102250 · Cited by 118 · see citing works
Virani, S. S., Nambi, V., & Ballantyne, C. M. (2021) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvab010 · Cited by 10 · see citing works
An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis
Talvio, K., Wagner, V. A., Minkeviciene, R., Kirkwood, J. S., Kulinich, A. O., Umemori, J., Bhatia, A., Hur, M., Käkelä, R., Ethell, I. M., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-05147-9 · Cited by 8 · see citing works
- Authors
- So, J., Wu, D., Lichtenstein, A. H., Tai, A. K., Matthan, N. R., Maddipati, K. R., & Lamon-Fava, S.
- Affiliations
- Tufts University (US)
- Wayne State University (US)
- ORCID
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 316
- Pages
- 90-98
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W3111775211
- Cited by
- 127
- References
- 5
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 29 · 2023: 14 · 2022: 27 · 2021: 20
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Atherosclerosis (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Agriculture
- National Institute of Food and Agriculture
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Physical Sciences › Chemistry › Organic Chemistry › Edible Oils Quality and Analysis
- Keywords
- eicosapentaenoic acid, docosahexaenoic acid, omega-3 supplementation, chronic inflammation, specialized pro-resolving mediators, polyunsaturated fatty acids, cytokine expression, TNF-α, IL-10, MCP-1, hydroxy fatty acids, docosapentaenoic acid, postmenopausal women
- MeSH terms
- Docosahexaenoic Acids, Double-Blind Method, Female, Humans, Inflammation, Male, Monocytes, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Cross-Over Studies, Dietary Supplements
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