{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:06:59Z","timestamp":1789081619338,"version":"build-2803163510"},"reference-count":42,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":225,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent evidence suggests that higher-than-recommended intakes of long-chain n-3 polyunsaturated fatty acids (PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are both safe and effective in supporting health conditions such as inflammatory diseases in adult humans. For adult dogs at maintenance, the National Research Council (NRC 2006) recommends a safe upper limit of EPA+DHA of 0.37\u2009g\/kg body weight (BW)0.75, a value based on limited evidence. This study aimed to investigate how low, moderate and high dietary intakes of EPA+DHA affected oxidative balance through \u03b1-tocopherol and malondialdehyde (MDA) concentrations, lipid incorporation into circulating phospholipid fractions, and serum cytokines in healthy adult dogs over 8\u2009wk. Twenty-seven client-owned dogs were enrolled and, following a 4-wk diet acclimation phase, were allocated into three groups balanced for age and BW and then randomly assigned to 1 of 3 dosage groups, consisting of 0.03\u2009g\/kg BW0.75 (LOW) of EPA+DHA, 0.45\u2009g\/kg BW0.75 (MOD), and 0.71\u2009g\/kg BW0.75 (HIGH). Fasted blood samples were collected at weeks 0, 4, and 8 to evaluate serum fatty acid (FA) composition within circulating phospholipid fractions, whole blood \u03b1-tocopherol, malondialdehyde (MDA), and cytokine concentrations. Data were analyzed using PROC GLIMMIX in SAS, with dog treated as a random effect, week as a repeated measure, and dosage group (DG), week, sex, and their interactions as fixed effects. In serum phosphatidylcholine (PC) and lysophosphatidylcholine (LysoPC) fractions, EPA and DHA incorporation increased from baseline to week 4 across all dosage groups, with no changes observed between weeks 4 and 8. Total FA analysis showed that dietary EPA+DHA increased total n-3 PUFA and reduced total n-6 PUFA, with both the MOD and HIGH being greater than the LOW treatment. Whole blood \u03b1-tocopherol concentrations showed a DG\u2009\u00d7\u2009week interaction (P\u2009=\u20090.034), with the LOW group (5.82\u2009\u00b5g\/mL) maintaining higher concentrations at week 8 than the HIGH group (3.52\u2009\u00b5g\/mL) and not differing from the MOD group (5.00\u2009\u00b5g\/mL). Overall, increasing dietary EPA+DHA intake in adult dogs enriched circulating and membrane-associated n-3 PUFA pools while maintaining MDA and inflammatory cytokine concentrations despite reduced \u03b1-tocopherol concentrations. This suggests that higher EPA+DHA intakes were well tolerated over the 8-wk study period when interpreted alongside antioxidant status.<\/jats:p>","DOI":"10.1093\/jas\/skag257","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:49:58Z","timestamp":1786686598000},"source":"Crossref","is-referenced-by-count":0,"title":["Revisiting eicosapentaenoic acid and docosahexaenoic acid recommendations for healthy Siberian Huskies at maintenance: greater dietary EPA and DHA increase plasma lipid incorporation and reduce \u03b1-tocopherol concentrations"],"prefix":"10.1093","volume":"104","author":[{"given":"Benjamin D","family":"Fox","sequence":"first","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Banton","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-2349","authenticated-orcid":false,"given":"Alexandra","family":"Rankovic","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"MacDonald Murray","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9756-6989","authenticated-orcid":false,"given":"Lindsey","family":"Rummell","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W L","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn M","family":"Hillyer","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Saunders-Blades","sequence":"additional","affiliation":[{"name":"Champion Petfoods Holding Inc. , Edmonton, AB T6X 0P8,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Kelly","sequence":"additional","affiliation":[{"name":"Champion Petfoods Holding Inc. , Edmonton, AB T6X 0P8,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Templeman","sequence":"additional","affiliation":[{"name":"Primal Pet Foods, Primal Pet Group , Fairfield, CA 94634,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay E","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Human Health and Nutritional Sciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-4774","authenticated-orcid":false,"given":"Anna K","family":"Shoveller","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph , Guelph, ON N1G 2W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026091018113807600_skag257-B0616340","volume-title":"Official publication","author":"AAFCO","year":"2026"},{"key":"2026091018113807600_skag257-B1","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s002510050532","article-title":"Cloning, sequencing, and characterization of dog interleukin-18","volume":"49","author":"Argyle","year":"1999","journal-title":"Immunogenetics"},{"key":"2026091018113807600_skag257-B6879811","author":"Association of American Feed Control Officials (AAFCO).","year":"2016","journal-title":"Official publication"},{"key":"2026091018113807600_skag257-B2","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.2460\/javma.239.11.1441","article-title":"Therapeutic use of fish oils in companion animals","volume":"239","author":"Bauer","year":"2011","journal-title":"J Am Vet Med Assoc"},{"key":"2026091018113807600_skag257-B3","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/0005-2760(94)00201-9","article-title":"Quantification of the interactions among fatty acid, lysophosphatidylcholine, calcium, dimyristoylphosphatidylcholine vesicles, and phospholipase A2","volume":"1254","author":"Bent","year":"1995","journal-title":"Biochim Biophys Acta"},{"key":"2026091018113807600_skag257-B4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3410\/f.734408621.793553112","article-title":"Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia","volume":"380","author":"Bhatt","year":"2019","journal-title":"N Engl J Med"},{"key":"2026091018113807600_skag257-B5","doi-asserted-by":"publisher","first-page":"101034","DOI":"10.1016\/j.animal.2023.101034","article-title":"Effects of dietary camelina, flaxseed, and canola oil supplementation on plasma fatty acid concentrations and health parameters in horses","volume":"17","author":"Burron","year":"2023","journal-title":"J Anim Sci"},{"key":"2026091018113807600_skag257-B6","doi-asserted-by":"publisher","first-page":"11161904","DOI":"10.1093\/jas\/skae143","article-title":"Review: Effects of dietary n-6 and n-3 fatty acid ratios on physiological and metabolic outcomes in companion and performance animals","volume":"11","author":"Burron","year":"2024","journal-title":"Front Vet Sci"},{"key":"2026091018113807600_skag257-B7","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.bbalip.2014.08.010","article-title":"Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance","volume":"1851","author":"Calder","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"2026091018113807600_skag257-B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-94-007-6331-9_1","article-title":"Lipid-mediated protein signaling: Sphingomyelin and its role in cellular signaling","volume":"991","author":"Chakraborty","year":"2013","journal-title":"Adv Exp Med Biol"},{"key":"2026091018113807600_skag257-B10","doi-asserted-by":"publisher","first-page":"7000","DOI":"10.1038\/ncomms8000","article-title":"Widespread seasonal gene expression reveals annual differences in human immunity and physiology","volume":"6","author":"Dopico","year":"2015","journal-title":"Nat Commun"},{"key":"2026091018113807600_skag257-B11","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s00232-011-9401-7","article-title":"Influence of phospholipid species on membrane fluidity: a meta-analysis for a novel phospholipid fluidity index","volume":"244","author":"Fajardo","year":"2011","journal-title":"J Membr Biol"},{"key":"2026091018113807600_skag257-B12","volume-title":"Nutritional guidelines for complete and complementary pet food for cats and dogs","author":"FEDIAF","year":"2026"},{"key":"2026091018113807600_skag257-B13","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1111\/j.1939-1676.2010.0572.x","article-title":"Dose-titration effects of fish oil in osteoarthritic dogs","volume":"24","author":"Fritsch","year":"2010","journal-title":"J Vet Intern Med"},{"key":"2026091018113807600_skag257-B14","doi-asserted-by":"publisher","first-page":"e0190474","DOI":"10.1371\/journal.pone.0190474","article-title":"MCP-1, KC-like and IL-8 as critical mediators of pathogenesis caused by Babesia canis","volume":"13","author":"Galan","year":"2018","journal-title":"PLoS One"},{"key":"2026091018113807600_skag257-B15","doi-asserted-by":"publisher","first-page":"e37","DOI":"10.1017\/jns.2017.30","article-title":"Effects of matrix on plasma levels of EPA and DHA in dogs","volume":"6","author":"Goffin","year":"2017","journal-title":"J Nutr Sci"},{"key":"2026091018113807600_skag257-B658496311","author":"Government of Ontario","year":"1990","journal-title":"Animals for research act, R.S.O. 1990."},{"key":"2026091018113807600_skag257-B16","doi-asserted-by":"publisher","first-page":"762","DOI":"10.2460\/ajvr.2003.64.762","article-title":"Effects of dietary n-6 and n-3 fatty acids and vitamin E on immune function in healthy dogs","volume":"64","author":"Hall","year":"2003","journal-title":"Am J Vet Res"},{"key":"2026091018113807600_skag257-B17","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1093\/jn\/136.9.2338","article-title":"The (n-3) fatty acid dose, independent of the (n-6)-to-(n-3) fatty acid ratio, affects the plasma fatty acid profile of normal dogs","volume":"136","author":"Hall","year":"2006","journal-title":"J Nutr"},{"key":"2026091018113807600_skag257-B18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/0006-8993(74)90356-4","article-title":"The turnover of myelin phosphatidylcholine and sphingomyelin in the adult rat brain","volume":"78","author":"Jungalwala","year":"1974","journal-title":"Brain Res"},{"key":"2026091018113807600_skag257-B19","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.vetimm.2016.01.005","article-title":"Multiplex cytokine analyses in dogs with pyometra suggest involvement of KC-like chemokine in canine bacterial sepsis","volume":"170","author":"Karlsson","year":"2016","journal-title":"Vet Immunol Immunopathol"},{"key":"2026091018113807600_skag257-B20","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0009-8981(03)00171-2","article-title":"Chronic cold exposure affects the antioxidant defense system in various rat tissues","volume":"333","author":"Kaushik","year":"2003","journal-title":"Clin Chim Acta"},{"key":"2026091018113807600_skag257-B21","first-page":"10","article-title":"Developmental and validation of a body condition score system for dogs","volume":"22","author":"Laflamme","year":"1997","journal-title":"Canine Pract"},{"key":"2026091018113807600_skag257-B22","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.31390\/gradschool_dissertations.2806","article-title":"Effect of dietary fish oil and vitamin E supplementation on hematologic and serum biochemical analytes and oxidative status in young dogs","volume":"66","author":"LeBlanc","year":"2005","journal-title":"Am J Vet Res"},{"key":"2026091018113807600_skag257-B23","doi-asserted-by":"publisher","first-page":"486","DOI":"10.2460\/ajvr.69.4.486","article-title":"Effects of dietary supplementation with fish oil on in vivo production of inflammatory mediators in clinically normal dogs","volume":"69","author":"LeBlanc","year":"2008","journal-title":"Am J Vet Res"},{"key":"2026091018113807600_skag257-B24","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1111\/jvim.12033","article-title":"Potential adverse effects of omega-3 fatty acids in dogs and cats","volume":"27","author":"Lenox","year":"2013","journal-title":"J Vet Intern Med"},{"key":"2026091018113807600_skag257-B25","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1249\/mss.0000000000003117","article-title":"The dose-response effect of docosahexaenoic acid on the omega-3 index in American football athletes","volume":"55","author":"Lust","year":"2023","journal-title":"Med Sci Sports Exerc"},{"key":"2026091018113807600_skag257-B26","doi-asserted-by":"publisher","first-page":"681","DOI":"10.3390\/antiox10050681","article-title":"Tissue antioxidant status and lipid peroxidation are modulated by dietary n-3 PUFA supplementation in rabbit bucks","volume":"10","author":"Mattioli","year":"2021","journal-title":"Antioxidants"},{"key":"2026091018113807600_skag257-B27","doi-asserted-by":"publisher","first-page":"12432","DOI":"10.1007\/s12035-021-02501-y","article-title":"Systemic elevation of n-3 polyunsaturated fatty acids protects against mild traumatic brain injury via reduced ceramide signaling","volume":"22","author":"Mondal","year":"2021","journal-title":"Int. J. Mol. Sci"},{"key":"2026091018113807600_skag257-B28","volume-title":"Nutrient requirements of dogs and cats","author":"NRC","year":"2006"},{"key":"2026091018113807600_skag257-B29","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1042\/bj1190481","article-title":"Turnover of mammalian phospholipids. Rates of turnover and metabolic heterogeneity in cultured human lymphocytes and in tissues of healthy, starved and vitamin A-deficient rats","volume":"119","author":"Pasternak","year":"1970","journal-title":"Biochem J"},{"key":"2026091018113807600_skag257-B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jas\/skaa057","article-title":"Effects of diet on body weight, body composition, metabolic status, and physical activity levels of adult female dogs after spay surgery","volume":"98","author":"Phungviwatnikul","year":"2020","journal-title":"J Anim Sci"},{"key":"2026091018113807600_skag257-B31","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.3390\/biom12081092","article-title":"The effect of fish oil\u2013based foods on lipid and oxidative status in police dogs","volume":"12","author":"Ravi\u0107","year":"2022","journal-title":"Biomolecules"},{"key":"2026091018113807600_skag257-B32","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1177\/0300985817725388","article-title":"Cytokine concentrations measured by multiplex assays in canine peripheral blood samples","volume":"55","author":"Richter","year":"2018","journal-title":"Vet Pathol"},{"key":"2026091018113807600_skag257-B34","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1111\/vde.12681","article-title":"Evaluation of immunological parameters in pit bull terrier-type dogs with juvenile onset generalized demodicosis and age-matched healthy pit bull terrier-type dogs","volume":"29","author":"Souza","year":"2018","journal-title":"Vet Dermatol"},{"key":"2026091018113807600_skag257-B36","doi-asserted-by":"publisher","first-page":"skab321","DOI":"10.3389\/fvets.2021.704770","article-title":"Dietary fatty acid profile and exercise modulate serum lipid fractions and oxidative status in sled dogs","volume":"99","author":"Templeman","year":"2021","journal-title":"J Anim Sci"},{"key":"2026091018113807600_skag257-B37","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.plefa.2015.01.005","article-title":"Fish oil supplementation increases n-3 fatty acids and decreases the n-6: n-3 ratio in bovine plasma and milk","volume":"98","author":"Thanh","year":"2015","journal-title":"J Dairy Sci"},{"key":"2026091018113807600_skag257-B38","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/s0002-8223(02)90346-9","article-title":"Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids","volume":"102","author":"Trumbo","year":"2002","journal-title":"J Am Diet Assoc"},{"key":"2026091018113807600_skag257-B39","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1746-6148-10-104","article-title":"Failure of a dietary model to affect markers of inflammation in domestic cats","volume":"10","author":"Verbrugghe","year":"2014","journal-title":"BMC Vet Res"},{"key":"2026091018113807600_skag257-B40","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1093\/jn\/127.6.1198","article-title":"The ratio of dietary (n-6) to (n-3) fatty acids influences immune system function, eicosanoid metabolism, lipid peroxidation and vitamin E status in aged dogs","volume":"127","author":"Wander","year":"1997","journal-title":"J Nutr"},{"key":"2026091018113807600_skag257-B41","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/s0140-6736(07)60527-3","article-title":"Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis","volume":"369","author":"Yokoyama","year":"2007","journal-title":"Lancet"},{"key":"2026091018113807600_skag257-B43","doi-asserted-by":"publisher","first-page":"8325","DOI":"10.3390\/ijms2515832","article-title":"Polar glycerolipids and membrane lipid rafts","volume":"25","author":"Zhukov","year":"2024","journal-title":"Int J Mol Sci"}],"container-title":["Journal of Animal Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jas\/advance-article-pdf\/doi\/10.1093\/jas\/skag257\/70648314\/skag257.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jas\/article-pdf\/doi\/10.1093\/jas\/skag257\/70648314\/skag257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jas\/article-pdf\/doi\/10.1093\/jas\/skag257\/70648314\/skag257.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:11:48Z","timestamp":1789078308000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jas\/article\/doi\/10.1093\/jas\/skag257\/8761384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":42,"URL":"https:\/\/doi.org\/10.1093\/jas\/skag257","relation":{},"ISSN":["0021-8812","1525-3163"],"issn-type":[{"value":"0021-8812","type":"print"},{"value":"1525-3163","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"skag257"}}