Newspaper people have a saying: “Don’t ruin a good story with too much research.”

That seems to have been the standard media approach to a study published in the Journal of the National Cancer Institute on the association of serum phospholipid long-chain omega-3 polyunsaturated fatty acids (PUFA) and the risk of prostate cancer.

Phospholipid omega-3 fatty acids are a biomarker of usual omega-3 fatty acid intake. Much research indicates that high plasma concentrations of omega-3 PUFA, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), are associated with reduced cardiovascular risk.

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Recently, a 16-year prospective observational study of 2,692 elderly adults who were free of cardiac disease found that subjects with high phospholipid concentrations had reduced total mortality compared with subjects with low concentrations, primarily due to lower cardiovascular mortality.1

Results like this have prompted many people to increase their omega-3 PUFA consumption, either by eating more fatty fish or taking fish oil supplements. The former seems to reduce the risk of coronary heart disease mortality and sudden cardiac death while the latter does not.2-5

However, nothing acts in isolation, and researchers at Ohio State University set out to investigate how plasma concentrations of phospholipids might be associated with prostate cancer risk.6 The case-control study examined data and plasma collected in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, prospective, placebo-controlled trial that tested whether supplementation with selenium and/or vitamin E, a fat-soluble antioxidant, reduces prostate cancer risk. Based on the trial results, it does not, and vitamin E supplementation may actually increase the risk of prostate cancer.

In this case-control study, 834 subjects from SELECT who developed prostate cancer and 1,393 subjects who did not develop the disease underwent phospholipid fatty acid assays. Prostate cancers were classified as high-grade (Gleason score 8-10 and 7 [4+3]) or low-grade (Gleason score 2-6 and 7 [3+4]; see Table 1 for details).7

Table 1. The Gleason Scoring System Low- and High-grade Patterns for Prostate Cancer

 Low-grade patterns Pattern 1

• Acini nodules are closely packed, uniform, medium-sized

Pattern 2
• Similar to pattern 1, but minimal infiltration at edge of nodule
• More loosely arranged
High-grade patterns
Pattern 3
• Variable in size, but generally smaller than patterns 1-2
• Infiltrates in/around acini
• Discrete glandular units
Pattern 4
• Large, fused glands
• Poorly formed with irregular borders
Pattern 5
• No differentiation
• Consists of solid sheets, cords, single cells
• Central necrosis surrounded by tumor masses
*NOTE: The scoring ranges from 2-10, where the two main patterns are added to provide the Gleason score.

Statistical analysis found that mean levels of total long-chain omega-3 PUFA were significantly higher in subjects with prostate cancer than in controls. The finding held for subjects with either low-grade or high-grade cancer. Concentrations of EPA, DPA, and DHA were significantly higher in the total prostate cancer group and the low-grade cancer group, and higher, but not significantly so, in the relatively small high-grade cancer group.

Compared with men in the lowest quartile of total long-chain omega-3 PUFA plasma levels, men in the highest quartile had a 43% increased risk for either grade of prostate cancer, a 44% increased risk for low-grade cancer, and a 71% increased risk for high-grade cancer. Each 50% increase in omega-3 PUFA taken was associated with a 22% to 25% increase in cancer risk.

The authors wrote that it is unclear why high concentrations of omega-3 PUFA would increase prostate cancer risk, but it is important to note that this study doesn’t prove that they do. By conducting an observational study, the researchers found an association, not a causal relationship. Moreover, they did not record their subjects’ intake of seafood or supplements, so they can’t say whether eating salmon or taking fish oil contributed to the increased risk of cancer.

Those subtleties apparently escaped the editors at CTV News, WebMD, and Time, all of which ran headlines implying that fish oil in any form is bad for the prostate. Buried in each story is an acknowledgment that this study doesn’t answer the question of whether or not eating a lot of fish or taking fish oil supplements is a good idea.

Nevertheless, these study results do suggest that men should think seriously about their prostate cancer risk, along with their cardiovascular risk, when considering dietary supplements.


  1. Mozaffarian D, Lemaitre RN, King IB, et al. Plasma phospholipid long-chain ω-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Ann Intern Med. 2013;158(7):515-25.
  2. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047-67.
  3. Zheng J, Huang T, Yu Y, et al. Fish consumption and CHD mortality: an updated meta-analysis of seventeen cohort studies. Public Health Nutr. 2012;15(4):725-37.
  4. Rizos EC, Ntzani EE, 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. 2012;308(10):1024-33.
  5. Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M, et al. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med. 2013;368(19):1800-8.
  6. Brasky TM, Darke AK, Song X, et al. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst. 2013 Jul 10. [Epub ahead of print]
  7. Epstein JI, Allsbrook WC, Amin MB, et al. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005 Sep;29(9):1228-42