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

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.