{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:47:31Z","timestamp":1785739651275,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Prospective studies of omega-3 supplementation during breast cancer chemotherapy differ in intervention composition, co-supplementation, dose, treatment setting, and outcomes. We summarized and critically appraised interventions comprising DHA alone, EPA + DHA, EPA + DHA + GLA, or EPA + DHA with or without vitamin D, stratified by intervention composition and outcome domain. Methods: PubMed\/MEDLINE, the Cochrane Library\/CENTRAL, ClinicalTrials.gov, Scopus, Web of Science Core Collection, and Embase were last searched on 8 July 2026, supplemented by citation searching. Eligible studies prospectively administered EPA and\/or DHA during chemotherapy and reported inflammatory\/biological, nutritional\/functional, quality-of-life, treatment-related, anticancer-response, or safety outcomes. Active co-supplementation was analyzed separately. Owing to clinical and methodological heterogeneity, findings were synthesized narratively; risk of bias and outcome-specific certainty were assessed using RoB 2-informed and GRADE approaches. Results: Fourteen reports representing ten prospective interventional trials were included. No eligible EPA-only trial was found. Interventions comprised EPA + DHA\/fish oil without another active nutrient, DHA alone, EPA + DHA plus gamma-linolenic acid, and a factorial trial of EPA + DHA with or without vitamin D. One trial reported lower paclitaxel-induced neuropathy, whereas another found no benefit for paclitaxel-associated acute pain or neuropathic symptoms. Biomarker, nutritional, functional, and quality-of-life findings were inconsistent and often derived from small trials, exploratory or compliance-restricted analyses, companion reports, or co-supplementation designs. No consistent improvement in treatment response or survival was demonstrated. Serious supplementation-related adverse events were not reported, although adverse-event reporting varied. Certainty was low for safety and very low for efficacy-related domains. Conclusions: Current evidence is preliminary. The evaluated interventions appeared generally tolerated, but independent clinical efficacy of DHA alone, EPA + DHA without another active nutrient, EPA + DHA + GLA, or EPA + DHA with or without vitamin D during breast cancer chemotherapy remains unproven.<\/jats:p>","DOI":"10.3390\/nu18152483","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:17:40Z","timestamp":1785737860000},"page":"2483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DHA Alone, EPA + DHA, EPA + DHA + GLA, and EPA + DHA with or Without Vitamin D During Chemotherapy in Women with Breast Cancer: An Intervention- and Outcome-Stratified Systematic Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Kinga","family":"Fronk","sequence":"first","affiliation":[{"name":"Independent Researcher, ul. Wilsona 20\/5, 33-100 Tarn\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8939-2490","authenticated-orcid":false,"given":"Mariusz","family":"Wysoki\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Fundamentals of Nursing, Chair of Nursing Development, Faculty of Health Sciences, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7565-7184","authenticated-orcid":false,"given":"Rafa\u0142","family":"Podg\u00f3rski","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rzesz\u00f3w, al. Tadeusza Rejtana 16C, 35-959 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4619-7705","authenticated-orcid":false,"given":"Edyta","family":"\u0141uszczki","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences and Psychology, University of Rzesz\u00f3w, al. Tadeusza Rejtana 16C, 35-959 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1002\/fsn3.3409","article-title":"The effectiveness of omega-3 fatty acids on health outcomes in women with breast cancer: A systematic review","volume":"11","author":"Mehdizadeh","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100464","DOI":"10.1016\/j.advnut.2025.100464","article-title":"Perspective: Implications of docosahexaenoic acid and eicosapentaenoic acid supplementation on the immune system during cancer chemotherapy: Perspectives from current clinical evidence","volume":"16","author":"Munhoz","year":"2025","journal-title":"Adv. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9503","DOI":"10.1074\/jbc.271.16.9503","article-title":"STAT3 participates in transcriptional activation of the C-reactive protein gene by interleukin-6","volume":"271","author":"Zhang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_4","first-page":"5139","article-title":"Prognostic impact of interleukin-6 and C-reactive protein on patients with breast cancer","volume":"17","author":"Shimura","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_7","unstructured":"Sch\u00fcnemann, H., Bro\u017cek, J., Guyatt, G., and Oxman, A. (2013). GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations, The GRADE Working Group. Available online: https:\/\/gradepro.org\/handbook\/."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ghoreishi, Z., Esfahani, A., Djazayeri, A., Djalali, M., Golestan, B., Ayromlou, H., Hashemzadeh, S., Asghari Jafarabadi, M., Montazeri, V., and Keshavarz, S.A. (2012). Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo-controlled trial. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-355"},{"key":"ref_9","first-page":"637","article-title":"A pilot randomized, placebo-controlled, double-blind study of omega-3 fatty acids to prevent paclitaxel-associated acute pain syndrome in breast cancer patients: Alliance A22_Pilot2. Support","volume":"31","author":"Tawfik","year":"2023","journal-title":"Care Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"911","DOI":"10.31557\/APJCP.2019.20.3.911","article-title":"Effects of omega-3 supplementation on Ki-67 and VEGF expression levels and clinical outcomes of locally advanced breast cancer patients treated with neoadjuvant CAF chemotherapy: A randomized controlled trial report","volume":"20","author":"Darwito","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1038\/sj.bjc.6605441","article-title":"Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: A phase II trial","volume":"101","author":"Bougnoux","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6449","DOI":"10.1038\/s41598-023-28411-8","article-title":"Anti-inflammatory effect of combining fish oil and evening primrose oil supplementation on breast cancer patients undergoing chemotherapy: A randomized placebo-controlled trial","volume":"13","author":"Arsic","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Almassri, H.F., Abdul Kadir, A., Srour, M., and Foo, L.H. (2024). The effects of omega-3 fatty acids and vitamin D supplementation on the nutritional status of women with breast cancer in Palestine: An open-label randomized controlled trial. Nutrients, 16.","DOI":"10.3390\/nu16223960"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/ijc.35517","article-title":"Safety and efficacy of docosahexaenoic acid supplementation during neoadjuvant breast cancer therapy: Findings from the phase II, double-blind, randomized controlled DHA-WIN trial","volume":"157","author":"Munhoz","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110025","DOI":"10.1016\/j.jnutbio.2025.110025","article-title":"The effects of docosahexaenoic acid (DHA) on plasma cytokines, oxylipins, and tumor-infiltrating lymphocytes from women with breast cancer undergoing neoadjuvant chemotherapy in the DHA-WIN trial","volume":"145","author":"Munhoz","year":"2025","journal-title":"J. Nutr. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13058-025-02048-z","article-title":"Docosahexaenoic acid (DHA) supplementation attenuates changes in the concentration, phenotype, and response of immune peripheral blood cells in breast cancer patients undergoing neoadjuvant therapy: Secondary findings from the DHA-WIN trial","volume":"27","author":"Munhoz","year":"2025","journal-title":"Breast Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Douglas, C.M., Newell, M., Goruk, S., Courneya, K.S., Ghosh, S., Joy, A.A., Munhoz, J., and Field, C.J. (2025). Exploratory outcomes of the DHA-WIN randomized controlled trial: Supplementing women with docosahexaenoic acid did not reduce the impact of neoadjuvant breast cancer chemotherapy on quality of life or exercise behaviour. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0322178"},{"key":"ref_18","first-page":"769","article-title":"Effects of omega-3 fatty acids supplementation on neoadjuvant chemotherapy-induced toxicity in patients with locally advanced breast cancer: A randomized, controlled, double-blinded clinical trial","volume":"36","author":"Miranda","year":"2019","journal-title":"Nutr. Hosp."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.clnesp.2024.11.014","article-title":"The effects of omega-3 fatty acids and vitamin D supplementation on the quality of life and blood inflammation markers in newly diagnosed women with breast cancer: An open-labelled randomised controlled trial","volume":"65","author":"Almassri","year":"2025","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1080\/01635581.2016.1187282","article-title":"Fish oil supplementation enhances pulmonary strength and endurance in women undergoing chemotherapy","volume":"68","author":"Suzumura","year":"2016","journal-title":"Nutr. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mantha, O.L., Hankard, R., Tea, I., Schiphorst, A.-M., Dumas, J.-F., Berger, V., Goupille, C., Bougnoux, P., and De Luca, A. (2022). N-3 fatty acid supplementation impacts protein metabolism faster than it lowers proinflammatory cytokines in advanced breast cancer patients: Natural 15N\/14N variations during a clinical trial. Metabolites, 12.","DOI":"10.3390\/metabo12100899"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"de Castro, G.S., Andrade, M.F., Pinto, F.C.S., Faiad, J.Z., and Seelaender, M. (2022). Omega-3 fatty acid supplementation and its impact on systemic inflammation and body weight in patients with cancer cachexia: A systematic review and meta-analysis. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.797513"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112466","DOI":"10.1016\/j.nut.2024.112466","article-title":"Does the ratio of eicosapentaenoic acid to docosahexaenoic acid matter in cancer treatment? A systematic review of their effects on cachexia-related inflammation","volume":"124","author":"Szlendak","year":"2024","journal-title":"Nutrition"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1017\/S000711450765795X","article-title":"N-3 fatty acids, cancer and cachexia: A systematic review of the literature","volume":"97","author":"Colomer","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_25","first-page":"360","article-title":"Effects of omega-3 fatty acids against chemotherapy-induced mucositis: A double-blind randomized clinical trial","volume":"29","author":"Hashemipour","year":"2017","journal-title":"Wounds"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.3889\/oamjms.2018.333","article-title":"Comparison of the effects of omega 3 and vitamin E on paclitaxel-induced peripheral neuropathy","volume":"6","author":"Anoushirvani","year":"2018","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13256-015-0619-3","article-title":"Improved antioxidant status by omega-3 fatty acid supplementation in breast cancer patients undergoing chemotherapy: A case series","volume":"9","author":"Mansara","year":"2015","journal-title":"J. Med. Case Rep."},{"key":"ref_28","first-page":"76","article-title":"Prediction of gastrointestinal symptom trajectories using omega-3 and inflammatory biomarkers in early-stage breast cancer patients receiving chemotherapy","volume":"32","author":"Arcos","year":"2024","journal-title":"Support. Care Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e030502","DOI":"10.1136\/bmjopen-2019-030502","article-title":"Comparing docosahexaenoic acid (DHA) concomitant with neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in the treatment of breast cancer (DHA WIN): Protocol of a double-blind, phase II, randomised controlled trial","volume":"9","author":"Newell","year":"2019","journal-title":"BMJ Open"},{"key":"ref_30","unstructured":"ClinicalTrials.gov (2026, June 12). Omega-3 Fatty Acids and Paclitaxel-Induced Neuropathy (NCT01049295), Available online: https:\/\/clinicaltrials.gov\/study\/NCT01049295."},{"key":"ref_31","first-page":"2","article-title":"Effect of supplementation with eicosapentaenoic and docosahexaenoic omega-3 polyunsaturated fatty acid on the chemotoxicity in Mexican patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NeoCT)","volume":"77","author":"Gomez","year":"2017","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/1538-7445.SABCS14-P3-13-08","article-title":"Modification of the response to chemotherapy of HER2-negative metastatic breast cancer by lipids of marine origin: A controlled, randomized, double-blind dietary supplementation trial","volume":"75","author":"Bougnoux","year":"2015","journal-title":"Cancer Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/15\/2483\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:27:38Z","timestamp":1785738458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/15\/2483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":32,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["nu18152483"],"URL":"https:\/\/doi.org\/10.3390\/nu18152483","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}