Omega-3


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Common Name: Polyunsaturated fatty acids (PUFAs)
Brand Names:  Omegaven, Max-EPA

The use of dietary supplements by patients with cancer has increased significantly over the past 2 decades despite insufficient evidence of safety and effectiveness. Finding reliable sources of information about dietary supplements can be daunting. Patients typically rely on family, friends, and the Internet, often receiving misleading information.

The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies commonly used by patients with cancer. We chose omega-3 fatty acids for this issue because of their growing use by cancer patients.

Compiled by Barrie R. Cassileth, PhD, and Jyothi Gubili, MS, Memorial Sloan-Kettering Cancer Center. The About Herbs website is managed by K. Simon Yeung, PharmD, MBA, Lac, Memorial Sloan-Kettering Cancer Center.

Overview

Omega-3 fatty acids are polyunsaturated fatty acids that play a crucial role in many physiologic processes. Because our bodies cannot synthesize them, omega-3s must be obtained through diet or dietary supplements. Good sources of omega-3 include fatty fish, some plants, and nut oils.

The three most studied omega-3s are alpha-linolenic acid, eicosapentanoic acid, and docosahexanoic acid. These are also the form most commonly used in dietary supplements. Following consumption, alpha-linolenic acid is converted to eicosapentanoic acid and docosahexanoic acid, forms that are readily used by the body. The current U.S. Food and Drug Administration recommendation is to limit intake of eicosapentanoic acid and docosahexanoic acid to 3 g/d (due to a potential risk of excessive bleeding in some individuals at higher intakes).

Available data strongly support the protective effects of omega-3s against cardiovascular disease. Benefits have been reported also for a wide range of conditions, including depression, inflammatory bowel disease, and autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. 

Omega-3s may play a role in cancer prevention, but definitive data are ­lacking.

The Science

A large survey of Finnish adults found that depressive symptoms were significantly higher among infrequent fish consumers.1 Supplementation with docosahexanoic acid improved learning and memory function in age-related cognitive decline,2 although data on omega-3 supplementation and cognition in young children3 and elderly subjects4 remain inconclusive.

Omega-3 supplements lowered cholesterol levels in individuals with hypercholesterolemia,5 and reduced recurrence in patients with history of stroke.6 In another study of patients with rheumatoid arthritis, omega-3 supplementation reduced nonsteroidal anti-inflammatory drug use.7 Fish oil also was shown to relieve symptoms associated with systemic lupus erythematosus.8 Findings of a systematic review support beneficial effects of omega-3 consumption on insulin sensitivity and adipocyte function.9

Omega-3s may reduce colon cancer risk10 and improve immune response in patients undergoing colorectal cancer resection,11 but they did not affect cancer outcomes.12 Similarly, studies of fish oil supplements suggest that they reduce the risk of breast cancer,13 but data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found increased risk of prostate cancer in patients with high blood levels of omega‑3.14 Further research is needed to determine the likely specific cancer preventive potential of omega-3s.

Preliminary findings from recent studies suggest that fish oil supplementation increases the efficacy of chemotherapy, improves survival,15 and helps maintain weight and muscle mass16 in patients with non–small cell lung cancer (NSCLC). Further, an eicosapentanoic acid–enriched oral supplement improved the tolerability of chemotherapy in patients with advanced colorectal cancer.17

Adverse Effects

Fishy aftertaste,10 loose stools, and nausea18 were reported after consuming large doses of omega-3 fatty acids.

Herb-Drug Interactions

Nonsteroidal anti-inflammatory drugs: Fish oil can have additive anticoagulant/antiplatelet effects,19 but a recent study reported that omega-3s do not affect coagulation or platelet function postsurgery.20

Lab Interactions

Omega-3s may reduce levels of alpha-tocopherol and beta-carotene.10,21

High levels of omega-3s may decrease triglycerides, and increase low-density lipoprotein cholesterol levels.22

Doses higher than 3 g/d may increase bleeding time.23

Disclosure: Ms. Gubili reported no potential conflicts of interest.

Guest Editor

Integrative Oncology is guest edited by Barrie R. Cassileth, MS, PhD, Chief of the Integrative Medicine Service and Laurance S. Rockefeller Chair in Integrative Medicine at Memorial Sloan-Kettering Cancer Center, New York.

The Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center developed and maintains a free website—About Herbs (www.mskcc.org/aboutherbs)—that provides objective and unbiased information about herbs, vitamins, minerals, and other dietary supplements, and unproved anticancer treatments. Each of the 265 and growing number of entries offer health-care professional and patient versions, and entries are regularly updated with the latest research findings.

In addition, the About Herbs app, Memorial Sloan-Kettering Cancer Center’s very first mobile application, was launched last fall. The app is compatible with iPad, iPhone, and iPod Touch devices, and can be downloaded at http://itunes.apple.com/us/app/about-herbs/id554267162?mt=8.

References

1. Tanskanen A, Hibbeln JR, Tuomilehto J, et al: Fish consumption and depressive symptoms in the general population in Finland. Psychiatr Serv 52:529-531, 2001.

2. Sinn N, Milte CM, Street SJ, et al: Br J Nutr. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: A 6-month randomised controlled trial. Br J Nutr 20:1-12, 2011.

3. Ryan AS, Nelson EB: Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: A randomized, placebo-controlled, double-blind study. Clin Pediatr (Phila) 47:355-362, 2008.

4. van de Rest O, Geleijnse JM, Kok FJ, et al: Effect of fish oil on cognitive performance in older subjects: A randomized, controlled trial. Neurology 71:430-438, 2008.

5. Gunnarsdottir I, Tomasson H, Kiely M, et al: Inclusion of fish or fish oil in weight-loss diets for young adults: Effects on blood lipids. Int J Obes 32:1105-1112, 2008.

6. Tanaka K, Ishikawa Y, Yokoyama M, et al: Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: Subanalysis of the JELIS trial. Stroke 39:2052-2058, 2008.

7. Galarraga B, Ho M, Youssef HM, et al: Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology (Oxford) 47:665-669, 2008.

8. Duffy EM, Meenagh GK, McMillan SA, et al: The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus. J. Rheumatology 31:1551-1556, 2004.

9. Wu JH, Cahill LE, Mozaffarian D: Effect of fish oil on circulating adiponectin: A systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 98:2451-2459, 2013.

10. Anti M, Armelao F, Marra G, et al: Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 107:1709-1718, 1994.

11. Liang B, Wang S, Ye YJ, et al: Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients. World J Gastroenterol 14:2434-2439, 2008.

12. Andreeva VA, Touvier M, Kesse-Guyot E, et al: B vitamin and/or ω-3 fatty acid supplementation and cancer: ancillary findings from the supplementation with folate, vitamins B6 and B12, and/or omega-3 fatty acids (SU.FOL.OM3) randomized trial. Arch Intern Med 172:540-547, 2012.

13. Brasky TM, Lampe JW, Potter JD, et al: Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Epidemiol Biomarkers Prev 19:1696-1708, 2010.

14. Brasky TM, Darke AK, Song X, et al: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst 105:1132-1141, 2013.

15. Murphy RA, Mourtzakis M, Chu QS, et al: Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer 117:3774-3780, 2011.

16. Murphy RA, Mourtzakis M, Chu QS, et al: Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer 117:1775-1782, 2011.

17. Trabal J, Leyes P, Forga M, et al: Potential usefulness of an EPA-enriched nutritional supplement on chemotherapy tolerability in cancer patients without overt malnutrition. Nutr Hosp 25:736-740, 2010.

18. Fugh-Berman A, Cott JM: Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med 61:712-728, 1999.

19. Haller C, Kearney T, Bent S, et al: Dietary supplement adverse events: Report of a one-year poison center surveillance project. J Med Toxicol 4:84-92, 2008.

20. Heller AR, Fischer S, Rossel T, et al: Impact of n-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery. Br J Nutr 87(suppl 1):S95-S101, 2002.

21. Holm T, Berge RK, Andreassen AK, et al: Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients. Transplantation 72:706-711, 2001.

22. Rizos E, Ntzani E, Bika E, et al: Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: A systematic review and meta-analysis. JAMA 308:1024-1033, 2012.

23. Lewis CJ: Letter Regarding Dietary Supplement Health Claim for Omega-3 Fatty Acids and Coronary Heart Disease. FDA Docket No. 91N-0103. Available at www.fda.gov/ohrms/dockets/DOCKETS/95s0316/95s-0316-Rpt0272-38-Appendix-D-Reference-F-FDA-vol205.pdf. Accessed August 28, 2013.



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