ReviewOmega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review
Introduction
The long chains polyunsaturated n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are naturally found in organisms of marine origin (e.g., fatty fish) and are present in oils extracted from these organisms (e.g. fish oils) [1]. DHA and EPA are incorporated as structural components into cell membrane phospholipids in the blood and tissues, and they mediate a number of biological effects [1]. They are involved in membrane organization, elasticity, ion permeability (including receptors, transporters, signaling proteins) and lipids mediators with less inflammatory and pro-resolving activity [2].
Cancer patients often suffer from metabolic alterations including inflammation; when associated with radiotherapy and chemotherapy there is more production of pro-inflammatory cytokines, prostaglandins and reactive oxygen/nitrogen species, inducing a cascade of events leading to a suppressed cellular immune function [3]. Omega-3 fatty acids have been considered potentially useful for adjuvant cancer therapy according to their properties on antitumor activity: anti-inflammatory, anti-proliferative, pro-apoptotic, anti-invasion, anti-metastatic and epigenetic regulation [4], [5], [6]. Accordingly, tumor cell response may be modified via multiple mechanisms [6], [7].
The results of in vitro and in vivo studies have suggested that DHA and EPA favorably modulate anticancer treatment responses – promote cytotoxic effects and improvement of several anticancer drugs in different human cancer cells line (leukemia, colorectal [8], [9], [10], lung, breast [11], [12], [13], cervical, neuroblastoma, lymphoid, pancreatic, bladder, ovarian, glioblastoma) [6], [7]. The results in humans seem to improve therapeutic outcome with fewer risks and side effects for patients [7], [8], [4]. Therefore, DHA and/or EPA can be administered in combination with chemotherapy or radiotherapy with a potential beneficial effect [14].
Based on the relevance of these results, clinical studies have been conducted to investigate whether supplementation of cancer therapy with omega-3 fatty acids improve chemotherapy and/or radiotherapy response. The aim of the present systematic review was to assess the effectiveness of EPA and/or DHA omega-3 fatty acid supplementation during chemotherapy and/or radiotherapy in outcome improvement. Better understanding the available results of EPA/DHA supplementation, in randomized controlled clinical studies, in terms of amount of dose, duration of supplementation and different outcomes could help to guide clinical practice.
Section snippets
Literature search
A systematic literature search of the PubMed database, EMBASE database, and Portal Periodicos CAPES was conducted in May 2014 to identify studies published on omega-3 supplements and cancer therapy. Two independent reviewers process the search and selection. The following search terms were used for a search of titles and Abstracts: “radiotherapy” or “chemotherapy” or “chemoradiotherapy” or “antineoplastic therapy” and “cancer”; or “neoplasm” or “tumor” or “oncol” or “carcinoma” or “malignant”
Results
We summarize 10 studies that met the selection criteria and provided data from 383 patients (Fig. 1). The cancers associated with these ten studies included breast (N = 1), colorectal (N = 3), lung (N = 4), gastrointestinal (N = 1), and an indeterminate cancer (N = 1). The treatments associated with these studies included radiotherapy (N = 1), chemotherapy (N = 8), and chemoradiotherapy (N = 1). There were two papers [18], [19] that were published on the same set of data, and they were
Discussion
In order for nutrition intervention in cancer to reach its potential, the nutrients involved and the timing of specific treatment doses need to be optimized to appropriately interfere with carcinogenesis and increase response rate to treatment [4]. Over the past 10 years, n-3 PUFA clinical trials were conducted but the clinical benefits remain unclear. Therefore we summarized the results of randomized controlled clinical trials involving EPA and DHA supplementation during cancer chemotherapy
Conclusion
When we included studies characterized by high quality methodology, the combination of fish oil supplements with conventional chemotherapy was beneficial. Moreover, none of the studies reported a worse outcome for the supplement patient groups. But since the number of cancer patients involved in these studies was limited, larger and specific cancer localization studies are needed to confirm these observations.
Author's contribution
JAPS (1) participated in the study design and conception, carried out all bibliographic research, interpreted data, and wrote the manuscript. MESF (2) performed data analysis and interpretation and revised the manuscript. DLW (3) participated in the design and conception of the study, oriented the bibliographic research, contributed to interpretation of the data, and revised and approved the manuscript.
Conflict of interest
The authors declare no conflict of interest.
Acknowledgment
We thank Ronald Koretz MD, PhD for the enlightning discussions on the technical planning which much contributed for the writing of this manuscript.
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