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Bioactive products formed in humans from fish oils
Open accessAbstract
Resolvins, maresins, and protectins can be formed from fish oils. These specialized pro-resolving mediators (SPMs) have been implicated in the resolution of inflammation. Synthetic versions of such SPMs exert anti-inflammatory effects in vitro and when administered to animal models. However, their importance as endogenous products formed in sufficient amounts to exert anti-inflammatory actions in vivo remains speculative. We biased our ability to detect SPMs formed in healthy volunteers by supplementing fish oil in doses shown previously to influence blood pressure and platelet aggregation under placebo-controlled conditions. Additionally, we sought to determine the relative formation of SPMs during an acute inflammatory response and its resolution, evoked in healthy volunteers by bacterial lipopolysaccharide (LPS). Bioactive lipids, enzymatic epoxyeicosatrienoic acids (EETs), and free radical-catalyzed prostanoids [isoprostanes (iPs)] formed from arachidonic acid and the fish oils, served as comparators. Despite the clear shift from ω-6 to ω-3 EETs and iPs, we failed to detect a consistent signal, in most cases, of SPM formation in urine or plasma in response to fish oil, and in all cases in response to LPS on a background of fish oil. Our results question the relevance of these SPMs to the putative anti-inflammatory effects of fish oils in humans.
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“another study did not detect consistent plasma levels of SPMs after fish oil dietary supplementation in healthy volunteers127.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [127]
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“A short term supplementation period of 17.6 g EPA and DHA/day did not result in the detection of these inflammatory resolving mediators in plasma or urine [152].”
From Omega-3 Fatty Acids and Skeletal Muscle Health (2015) · cites this paper as [152]
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“a recent study has called into question the production of inflammatory resolving molecules and their role in mediating inflammatory challenges in healthy humans [152].”
From Omega-3 Fatty Acids and Skeletal Muscle Health (2015) · cites this paper as [152]
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Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189
Prostaglandins and Inflammation
Ricciotti, E., & FitzGerald, G. A. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.207449 · Cited by 4,035
Self-citationPro-resolving lipid mediators are leads for resolution physiology
Serhan, C. N. (2014) · Nature · doi:10.1038/nature13479 · Cited by 3,041
Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60527-3 · Cited by 2,516
(1999) · PubMed · Cited by 2,062
Psychogios, N., Hau, D., Peng, J., Guo, A. C., Mandal, R., Bouatra, S., Sinelnikov, I. V., Krishnamurthy, R., Eisner, R., Gautam, B., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016957 · Cited by 1,779
Resolvin E1 and protectin D1 activate inflammation-resolution programmes
Schwab, J. M., Chiang, N., Arita, M., & Serhan, C. N. (2007) · Nature · doi:10.1038/nature05877 · Cited by 1,219
Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., & Gronert, K. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.8.1197 · Cited by 1,189
Fish and Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease in Women
Hu, F. B. (2002) · JAMA · doi:10.1001/jama.287.14.1815 · Cited by 1,018
Hong, S., Gronert, K., Devchand, P. R., Moussignac, R.-L., & Serhan, C. N. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300218200 · Cited by 1,000
Wang, C., Harris, W. S., Chung, M., Lichtenstein, A. H., Balk, E. M., Kupelnick, B., Jordan, H. S., & Lau, J. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.1.5 · Cited by 980
Arita, M., Bianchini, F., Aliberti, J., Sher, A., Chiang, N., Hong, S., Yang, R., Petasis, N. A., & Serhan, C. N. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042031 · Cited by 943
Fish consumption and the 30-year risk of fatal myocardial infarction
Daviglus, M. L., Stamler, J., Orencia, A. J., Dyer, A. R., Liu, K., Greenland, P., Walsh, M. K., Morris, D., & Shekelle, R. B. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704103361502 · Cited by 902
Does fish oil lower blood pressure? A meta-analysis of controlled trials.
Morris, M. C., Sacks, F. M., & ROSNER, B. A. (1993) · Circulation · doi:10.1161/01.cir.88.2.523 · Cited by 687
Hooper, L., Thompson, R. L., Harrison, R. A., Summerbell, C. D., Ness, A. R., Moore, H. J., Worthington, H. V., Durrington, P. N., Higgins, J. P. T., Capps, N. E., et al. (2006) · BMJ · doi:10.1136/bmj.38755.366331.2f · Cited by 676
Arita, M., Ohira, T., Sun, Y., Elangovan, S., Chiang, N., & Serhan, C. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3912 · Cited by 648
n–3 Fatty Acids in Cardiovascular Disease
Caterina, R. D. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1008153 · Cited by 572
Resolvins, Specialized Proresolving Lipid Mediators, and Their Potential Roles in Metabolic Diseases
Spite, M., Clària, J., & Serhan, C. N. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.006 · Cited by 464
RvE1 protects from local inflammation and osteoclastmediated bone destruction in periodontitis
Hastürk, H., Kantarcı, A., Ohira, T., Arita, M., Ebrahimi, N., Chiang, N., Petasis, N. A., Levy, B. D., Serhan, C. N., & Dyke, T. E. V. (2005) · The FASEB Journal · doi:10.1096/fj.05-4724fje · Cited by 444
Colas, R. A., Shinohara, M., Dalli, J., Chiang, N., & Serhan, C. N. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00024.2014 · Cited by 437
Knapp, H. R., Reilly, I. A. G., Alessandrini, P., & FitzGerald, G. A. (1986) · New England Journal of Medicine · doi:10.1056/nejm198604103141501 · Cited by 417
Self-citationThe Antihypertensive Effects of Fish Oil
Knapp, H. R., & FitzGerald, G. A. (1989) · New England Journal of Medicine · doi:10.1056/nejm198904203201603 · Cited by 405
Self-citationWada, M., DeLong, C. J., Hong, Y. H., Rieke, C. J., Song, I., Sidhu, R. S., Yuan, C., Warnock, M., Schmaier, A. H., Yokoyama, C., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703169200 · Cited by 400
Self-citationIsoprostanes: Formation, Analysis and Use As Indices of Lipid Peroxidation in Vivo
Lawson, J. A., FitzGerald, G. A., & Rokach, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.35.24441 · Cited by 381
Self-citationResolution of inflammation is altered in Alzheimer's disease
Wang, X., Zhu, M., Hjorth, E., Cortés‐Toro, V., Eyjolfsdottir, H., Graff, C., Nennesmo, I., Palmblad, J., Eriksdotter, M., Sambamurti, K., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.12.024 · Cited by 301
Oh, S. F., Pillai, P. S., Recchiuti, A., Yang, R., & Serhan, C. N. (2011) · Journal of Clinical Investigation · doi:10.1172/jci42545 · Cited by 292
Fish oil — How does it reduce plasma triglycerides?
Shearer, G. C., Savinova, O. V., & Harris, W. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.10.011 · Cited by 285
Mas, E., Croft, K. D., Zahra, P., Barden, A., & Mori, T. A. (2012) · Clinical Chemistry · doi:10.1373/clinchem.2012.190199 · Cited by 270
Tjonahen, E., Oh, S. F., Siegelman, J. N., Elangovan, S., Percarpio, K. B., Hong, S., Arita, M., & Serhan, C. N. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.09.011 · Cited by 249
Isobe, Y., Arita, M., Matsueda, S., Iwamoto, R., Fujihara, T., Nakanishi, H., Taguchi, R., Masuda, K., Sasaki, K. A., Urabe, D., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.340612 · Cited by 244
Seki, H., Fukunaga, K., Arita, M., Arai, H., Nakanishi, H., Taguchi, R., Miyasho, T., Takamiya, R., Asano, K., Ishizaka, A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901809 · Cited by 227
Fischer, R., Konkel, A., Mehling, H., Blossey, K., Gapelyuk, A., Wessel, N., von Schacky, C., Dechend, R., Müller, D. N., Rothe, M., et al. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m047357 · Cited by 219
Giera, M. A., Ioan‐Facsinay, A., Toes, R. E. M., Gao, F., Dalli, J., Deelder, A. M., Serhan, C. N., & Mayboroda, O. A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.07.011 · Cited by 210
Ho, K. J., Spite, M., Owens, C. D., Lancero, H., Kroemer, A. H. K., Pande, R., Creager, M. A., Serhan, C. N., & Conte, M. S. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.091082 · Cited by 204
Otto, M. C. D. O., Wu, J. H. Y., Baylín, A., Vaidya, D. M., Rich, S. S., Tsai, M. Y., Jacobs, D. R., & Mozaffarian, D. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000506 · Cited by 179
Resolvin E1 protects the rat heart against reperfusion injury
Keyes, K. T., Ye, Y., Lin, Y., Zhang, C., Perez-Polo, J. R., Gjorstrup, P., & Birnbaum, Y. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01057.2009 · Cited by 167
Liao, Z., Dong, J., Wu, W., Yang, T., Wang, T., Guo, L., Chen, L., Xu, D., & Wen, F. (2012) · Respiratory Research · doi:10.1186/1465-9921-13-110 · Cited by 149
Diversity of lipid mediators in human adipose tissue depots
Clària, J., Nguyen, B. T., Madenci, A. L., Ozaki, C. K., & Serhan, C. N. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00351.2012 · Cited by 136
Miyahara, T., Runge, S. J., Chatterjee, A., Chen, M., Mottola, G., Fitzgerald, J. M., Serhan, C. N., & Conte, M. S. (2013) · The FASEB Journal · doi:10.1096/fj.12-225615 · Cited by 134
Moertl, D., Hammer, A., Steiner, S., Hutuleac, R., Vonbank, K., & Berger, R. (2011) · American Heart Journal · doi:10.1016/j.ahj.2011.02.011 · Cited by 124
Weiss, G. A., Troxler, H., Klinke, G., Rogler, D., Braegger, C., & Hersberger, M. (2013) · Lipids in Health and Disease · doi:10.1186/1476-511x-12-89 · Cited by 120
Wang, Q., Zheng, X., Yang, C. H., Zhang, Y.-L., Wen, H.-X., Tao, Z., Li, H., Yu, H., Gao, Y., Yang, L.-M., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302421 · Cited by 116
Prüß, H., Rosche, B., Sullivan, A. B., Brommer, B., Wengert, O., Gronert, K., & Schwab, J. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055859 · Cited by 103
Keelan, J. A., Mas, E., D’Vaz, N., Dunstan, J. A., Li, S., Barden, A. E., Mark, P. J., Waddell, B. J., Prescott, S. L., & Mori, T. A. (2014) · Reproduction · doi:10.1530/rep-14-0549 · Cited by 100
Amano, T., Matsubara, T., Uetani, T., Kato, M., Kato, B., Yoshida, T., Harada, K., Kumagai, S., Kunimura, A., Shinbo, Y., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.05.030 · Cited by 83
Dawczynski, C., Massey, K. A., Ness, C., Kiehntopf, M., Stepanow, S., Platzer, M., Grün, M., Nicolaou, A., & Jahreis, G. (2012) · Clinical Nutrition · doi:10.1016/j.clnu.2012.12.010 · Cited by 77
(2012) · Europe PMC (PubMed Central) · Cited by 75
Balas, L., Guichardant, M., Durand, T., & Lagarde, M. (2013) · Biochimie · doi:10.1016/j.biochi.2013.11.006 · Cited by 74
Song, W., Lawson, J. A., Wang, M., Zou, H. Y., & FitzGerald, G. A. (2007) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)33003-6 · Cited by 65
Self-citationDetermination of ω-6 and ω-3 PUFA metabolites in human urine samples using UPLC/MS/MS
Sasaki, A., Fukuda, H., Shiida, N., Tanaka, N. K., Furugen, A., Ogura, J., Shuto, S., Mano, N., & Yamaguchi, H. (2015) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-014-8412-5 · Cited by 58
Resolvin D1 Reduces the Immunoinflammatory Response of the Rat Eye following Uveitis
Settimio, R., Filippo, C. D., Ferraraccio, F., Simonelli, F., & D'AMICO, M. (2012) · Mediators of Inflammation · doi:10.1155/2012/318621 · Cited by 56
Pedersen, A. K., & FitzGerald, G. A. (1985) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1985.8 · Cited by 53
Self-citationRecchiuti, A., Codagnone, M., Pierdomenico, A. M., Rossi, C., Mari, V. C., Cianci, E., Simiele, F., Gatta, V., & Romano, M. (2014) · The FASEB Journal · doi:10.1096/fj.13-248393 · Cited by 50
Omega‐3 PUFA supplementation and the response to evoked endotoxemia in healthy volunteers
Ferguson, J. F., Mulvey, C. K., Patel, P., Shah, R. Y., Doveikis, J., Zhang, W., Tabita‐Martinez, J., Terembula, K., Eiden, M. J., Koulman, A., et al. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300368 · Cited by 48
Self-citationKalish, B. T., Le, H. D., Fitzgerald, J. M., Wang, S., Seamon, K. J., Gura, K. M., Gronert, K., & Puder, M. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00106.2013 · Cited by 47
Total synthesis of the macrophage derived anti-inflammatory lipid mediator Maresin 1
Rodrı́guez, A. R., & Spur, B. W. (2012) · Tetrahedron Letters · doi:10.1016/j.tetlet.2012.05.143 · Cited by 37
Jacobo, S. H., Chang, C.-T., Lee, G., Lawson, J. A., Powell, W. S., Praticò, D., FitzGerald, G. A., & Rokach, J. (2006) · The Journal of Organic Chemistry · doi:10.1021/jo051916x · Cited by 35
Self-citationCell-Cell Interaction in the Transcellular Biosynthesis of Novel ω-3-Derived Lipid Mediators
Chiang, N., & Serhan, C. N. (2006) · Humana Press eBooks · doi:10.1385/1-59745-113-4:227 · Cited by 29
Hu (2012) · doi:10.1001/archinternmed.2012.463 · Cited by 26
Total synthesis of Resolvin D1, a potent anti-inflammatory lipid mediator
Rodríguez, A. R., & Spur, B. W. (2012) · Tetrahedron Letters · doi:10.1016/j.tetlet.2012.10.059 · Cited by 19
Eicosapentaenoic-acid-derived isoprostanes: Synthesis and discovery of two major isoprostanes
Chang, C.-T., Patel, P., Kang, N., Lawson, J. A., Song, W., Powell, W. S., FitzGerald, G. A., & Rokach, J. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.09.008 · Cited by 14
Self-citationA comparison between the concentration of prostaglandin F in human plasma and serum
Challis, J. R. G., & Tulchinsky, D. (1974) · Prostaglandins · doi:10.1016/s0090-6980(74)80127-9 · Cited by 12
iPF2α-III-17,18,19,20-d4: Total synthesis and metabolism
Kim, S., Powell, W. S., Lawson, J. A., Jacobo, S. H., Praticò, D., FitzGerald, G. A., Maxey, K. M., & Rokach, J. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.01.062 · Cited by 8
Self-citationChang, C.-T., Patel, P., Gore, V., Song, W., Lawson, J. A., Powell, W. S., FitzGerald, G. A., & Rokach, J. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.09.099 · Cited by 3
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Metadata
- Authors
- Skarke, C., Alamuddin, N., Lawson, J. A., Li, X., Ferguson, J. F., Reilly, M. P., & FitzGerald, G. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Skarke, Carsten
- FitzGerald, Garret A.
- ORCID
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 56
- Issue
- 9
- Pages
- 1808-1820
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC4548785
- OpenAlex
- W2270563637
- Cited by
- 109
- References
- 66
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 15 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 15 · 2016: 9 · 2015: 7
- FWCI
- 12.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (KL2TR000139, UL1TR000003, 2kl2rr024132-06)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK058404)
- National Institute of Environmental Health Sciences (P30ES013508)
- National Center for Research Resources (KL2-RR024132, UL1RR024134)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- fish oil, resolvins, maresins, protectins, specialized pro-resolving mediators, inflammation resolution, anti-inflammatory activity, omega-3 fatty acids, omega-6 fatty acids, epoxyeicosatrienoic acids, isoprostanes, lipopolysaccharide, acute inflammation, urinary biomarkers, plasma biomarkers, dietary supplementation
- MeSH terms
- Adult, Anti-Inflammatory Agents, Female, Fish Oils, Humans, Inflammation, Lipopolysaccharides, Male, Fatty Acids, Omega-3, Inflammation Mediators, CD59 Antigens, Dietary Supplements, Lipid Metabolism, Healthy Volunteers
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