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# Effects of Omega-3 Fatty Acids on Cancer

*Evidence Reports/Technology Assessments, No. 113*

Catherine H MacLean, MD, PhD, Task Order Director and Sydne J Newberry, PhD, Editor. Scientific Reviewers: Walter A Mojica, MD, MPH, Amalia Issa, PhD, Puja Khanna, MD, MPH, and Yee-Wei Lim, PhD. Statisticians: Sally C Morton, PhD, Program Director, Marika Suttorp, MS, and Wenli Tu, MS. Lara G Hilton, BA, Programmer/Analyst, Rena Hasenfeld Garland, BA, Project Manager, Shana Traina, MA, Staff Assistant, and Paul G Shekelle, MD, PhD, Program Director.

Agency for Healthcare Research and Quality (US)2005 Feb

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## Structured Abstract

#### Context:

Clinical trials and observational studies report differing                effects of omega-3 fatty acids on cancer.

#### Objectives:

To assess the effect of omega-3 fatty acids on 1) tumor                incidence 2) clinical outcomes after cancer treatment, and 3) tumor behavior.

#### Data Sources:

We searched computerized databases to identify                potentially relevant studies and contacted industry experts for unpublished                data.

#### Study Selection:

*Tumor incidence and outcomes after cancer treatment.* We screened                4,834 titles, reviewed 356 articles, and included 52 articles in our review. For                tumor incidence, we restricted to prospective cohort studies in humans, and for                clinical outcomes after cancer treatment, we restricted to randomized controlled                trials (RCTs); We had no language restrictions.

*Tumor behavior.* We screened 366 titles, reviewed 82 articles, and                included 27 articles in our review. For tumor behavior, we restricted to review                articles and meta-analyses of animal studies and cell culture studies in humans and                animals. We had no language restrictions.

#### Data Extraction:

We abstracted data on study design, study population,                and outcomes; source, amount, and duration of omega-3 fatty acid consumption; and                randomization, dropouts, blinding, and allocation for RCTs.

#### Data Synthesis:

*Tumor incidence.* Across 19 cohorts for 11 different types of cancer                and using up to 5 different ways to categorize omega-3 fatty acid consumption, 44                estimates of the association between omega-3 fatty acid consumption were reported.                Among these, only six were statistically significant. Significant associations                between omega-3 consumption (in the form of both fish and alpha-linolenic acid) and                cancer risk were reported for breast cancer in two studies; for lung cancer in two;                for prostate cancer in one; and for skin cancer in one. For breast cancer one                significant estimate was for increased risk and one was for decreased risk; five                other estimates did not show a significant association. For lung cancer one of the                significant associations was for increased cancer risk, the other was for decreased                risk and four other estimates were not significant. Only one study assessed skin                cancer risk.

*Cancer treatment.* We identified 19 studies from which the effect of                omega-3 fatty acids on clinical outcomes after cancer therapy could be ascertained,                all of which pertained to patients who had undergone cancer surgery for upper                gastrointestinal malignancies. We did not identify any studies that assessed the                effects of omega-3 fatty acids on clinical outcomes after chemotherapy or radiation                treatment. Among the identified studies, the effect of omega-3 fatty acids alone                could be ascertained from six studies; the effect of omega-3 fatty acids given in                combination with arginine and RNA could be ascertained from 13. Effects on                post-operative complications were described in 14, on hospital length of stay in 13,                on mortality in ten, on nutritional parameters in 11, and on weight in three. In                pooled analyses, omega-3 fatty acids had no effect compared to placebo on                post-operative complications, hospital length of stay, nutritional parameters, or                mortality.

Relative to a standard enteral diet, omega-3 fatty acids in combination with arginine                and RNA were associated with a reduced risk of postoperative complications (RR 0.51,                95%CI 0.40, 0.64) and reduced length of hospital stay (pooled mean difference -3.33                days, 95%CI -4.29, -2.38). Among nine studies that assessed the effect on                nutritional parameters omega-3 plus arginine and RNA, prealbumin was significantly                higher in the omega-3 + arginine + RNA group in three studies, but not different in                three others; mean nitrogen intake was significantly higher in one study but not in                another. No significant differences were found for mean caloric intake, mean                albumin, or mean transferrin.

Although the combination of omega-3 fatty acids, arginine, and RNA are associated                with a reduced risk of post-operative complications and reduced length of hospital                stay, it is not possible to ascertain whether these effects are due to omega-3 fatty                acids, arginine, RNA, or a combination of these.

*Tumor behavior.* We evaluated 27 reviews of studies on animals or                cell culture models that described the effects of tumor growth, differentiation or                apoptosis. Although much of the evidence favored a role for n-3 dietary enrichment                in the inhibition or prevention of tumor growth, at least in some animal models, the                quality of the reviews is not sufficient to permit strong conclusions to be                drawn.

#### Conclusions:

In a large body of literature spanning numerous cohorts                from many countries and with different demographic characteristics, the evidence                does not suggest a significant association between omega-3 fatty acids and cancer                incidence. In a small body of literature, there is no significant association                between omega-3 fatty acids and clinical outcomes after tumor surgery. Although the                combination of omega-3 fatty acids, arginine, and RNA are associated with a reduced                risk of post-operative complications and reduced length of hospital stay, it is not                possible to ascertain whether these effects are due to omega-3 fatty acids,                arginine, RNA, or a combination of these. Although a large, but heterogeneous, body                of literature suggests that omega-3 dietary enrichment may play a favorable role in                the inhibition or prevention of tumor growth in some animal models, the quality of                the reviews is not sufficient to permit strong conclusions to be drawn.

## Contents

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                        - Preface
                        - Acknowledgments
                        - 1. Introduction                           - The Recognition of Essential Fatty Acids
                          - Fatty Acid Nomenclature
                          - Fatty Acid Metabolism
                          - Physiological Functions of EPA and AA
                          - Dietary Sources and Requirements
                          - Rationale for and Organization of this Report
                        - 2. Methodology                           - Objectives
                          - Scope of Work
                          - Original Proposed Key Questions
                          - Technical Expert Panel
                          - Key Questions Addressed in this Report
                          - Identification of Literature Sources
                          - Evaluation of Evidence
                          - Extraction of Data
                          - Grading Evidence
                          - Data Synthesis
                          - Meta-Analysis
                          - Trial Summary Statistics
                          - Performance of Meta-Analysis
                          - Sensitivity Analyses
                          - Publication Bias
                          - Interpretation of the Results
                          - Peer Review
                        - 3. Results                           - Results of Literature Search
                          - Tumor Incidence
                          - Cohort Characteristics
                          - Overall Effect of Omega-3 FA on Tumor Incidence
                          - Modification of Effects of Omega-3 Fatty Acids on Tumor Incidence
                          - Effects on Clinical Outcomes After Cancer Treatment
                          - Cancer Chemotherapy
                          - Cancer Radiation Therapy
                          - Modification of Effects of Omega-3 FA on Tumor Treatment
                          - Tumor Behavior: Effects of n-3 Fatty Acids on Tumor Growth, Apoptosis, and Cell Differentiation in Animal and Cell Culture Models
                        - 4. Discussion                           - Overview
                          - Main Findings
                          - Limitations
                          - Conclusions
                          - Future Research
                        - Acronyms
                        - Appendix A. Methodologic Approach
                        - Appendix B. Coding/Data Abstraction Forms
                        - Appendix C. Evidence Tables
                        - References and Included Studies
                        - Listing of Excluded Studies

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                          - Collapse All

Librarians: Jessie McGowan, MLIS, Nancy Santesso, RD, MLIS. Staff Assistants:                    Shannon Rhodes, MFA, Cony Rolon, BA.

Prepared for: Agency for                    Healthcare Research and Quality, U.S. Department of Health                and Human Services.1                 Contract No. 290-02-0003. Prepared by:                Southern California/RANDEvidence-based Practice Center, Los Angeles, CA.

#### Suggested citation:

MacLean CH, Newberry SJ, Mojica, WA, Issa A, Khanna                    P, Lim YW, Morton SC, Suttorp M, Tu W, Hilton LG, Garland RH, Traina SB,                    Shekelle PG. Effects of Omega-3 Fatty Acids on Cancer. Evidence                    Report/Technology Assessment No. 113. (Prepared by the Southern California                    Evidence-based Practice Center, under Contract No. 290-02-0003.) AHRQ                    Publication No. 05-E010-2. Rockville, MD. Agency for Healthcare Research and                    Quality. February 2005.

This report may be used, in whole or in part, as the basis for development of                clinical practice guidelines and other quality enhancement tools, or a basis for                reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human                Services endorsement of such derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve                the quality of health care, reduce its cost, address patient safety and medical                errors, and broaden access to essential services. AHRQ sponsors and conducts                research that provides evidence-based information on health care outcomes; quality;                and cost, use, and access. The information helps health care decision                makers—patients and clinicians, health system leaders, and policymakers—make more                informed decisions and improve the quality of health care services.

The authors of this report are responsible for its content. Statements in the report                should not be construed as endorsement by the Agency for Healthcare Research and                Quality or the U.S. Department of Health and Human Services of a particular drug,                device, test, treatment, or other clinical service.

                        - 1
                        - 
540 Gaither Road, Rockville, MD 20850. www​.ahrq.gov

Copyright Notice

Bookshelf ID: NBK37626

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                    - Cite this Page MacLean CH, Newberry SJ, Mojica WA, et al. Effects of Omega-3 Fatty Acids on Cancer. Rockville (MD): Agency for Healthcare Research and Quality (US); 2005 Feb. (Evidence Reports/Technology Assessments, No. 113.)

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