Perspective: Implications of Docosahexaenoic Acid and Eicosapentaenoic Acid Supplementation on the Immune System during Cancer Chemotherapy: Perspectives from Current Clinical Evidence

Abstract

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) with pleiotropic effects on the immune system. Although several preclinical studies support their potential to enhance cancer treatment efficacy, this has not yet been translated into clinical studies. Currently, there are no official recommendations for n-3 LCPUFAs supplementation during cancer chemotherapy. This review examined human studies that supplemented DHA and/or EPA in patients with cancer undergoing chemotherapy, aiming to evaluate n-3 LCPUFAs effects on immune outcomes. A systematic search was conducted using electronic databases, including OvidMedline and the Global Organization for EPA and DHA Omega-3s Clinical Study Database. Twelve studies were included in this review. EPA+DHA doses ranged from 0.6 to 4 g/d, and intervention durations ranged from 6 wk to 6 mo. Most of the studies demonstrated changes in some immune-related outcomes, including reductions in the blood markers of inflammation (interleukin-6 and C-reactive protein), a lower incidence of adverse events, and the preservation of immune cell concentrations and functions (phagocytosis and hydrogen peroxide production). However, caution is warranted due to the limited number of studies and the heterogeneity of study designs. This review discusses the limitations of current studies and the mechanistic evidence supporting the investigation and potential use of n-3 LCPUFAs during cancer chemotherapy. Future research should focus on addressing these limitations by conducting well-designed, large-scale clinical trials that clearly report the dose and duration of n-3 LCPUFAs supplementation during specific chemotherapy regimens. Despite some promising outcomes, more evidence will be needed before recommending n-3 LCPUFAs supplementation as part of chemotherapy regimens aimed at attenuating chemotherapy-induced immune alterations.

Keywords: chemotherapy; dietary supplements; docosahexaenoic acid; eicosapentaenoic acid; immune function; inflammation; omega-3 fatty acids.

FIGURE 1

Summary of the current evidence from studies on the beneficial effects of n-3 long-chain PUFAs supplementation on immune and hematologic outcomes during cancer chemotherapy. The data for this figure are derived from the studies described in Table 1. (A) Findings summarized by cancer type. (B) Findings summarized by immune-related and hematologic outcomes. CRP, C-reactive protein; PMN, polymorphonuclear. Created in BioRender. Munhoz, J. (2025) https://BioRender.com/59hmnq9

FIGURE 2

Proposed model of study components for higher-quality evidence. The initial steps involve the study design and include sample size calculation, definition of the study protocol based on existing literature, assessment of confounding factors and compliance, and evaluation of multiple timepoints. Ideally, studies aimed at evaluating immune outcomes should expand their methods to include inflammatory markers, cellular immunity, and functional assays, and integrate these with mechanisms and clinical outcomes. Lastly, studies should report findings based on robust statistical analyses and follow established guidelines (for example, CONSORT checklist) for clear and transparent reporting. Together, these steps have the potential to enhance reproducibility and consistency across studies and facilitate the translation of findings into treatment recommendations. IFN-γ, interferon gamma; TGF-β, transforming growth factor beta. Created in BioRender. Munhoz, J. (2025) https://BioRender.com/z47qrdk