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How a Bad Study Became Big News
Michael T. Murray, ND
n July 10, 2013, major media headlines and news stories claimed “Too Much Fish Oil Might Boost Prostate Cancer Risk.” Wow, that sure seems “fishy” given all of the positive health benefits linked to fish oil intake. In examining the study, there are numerous issues that clearly indicate that perhaps the conclusion is wrong, but really a study’s conclusion is only as good as the data used (garbage in = garbage out). Data Used Was From SELECT The pedigree of the study source is impressive. It was published in the Journal of the National Cancer Institute and was conducted by researchers from the Fred Hutchinson Cancer Research Center in Seattle, Washington.1 Yet, the data they used is from the much maligned Selenium and Vitamin E Cancer Prevention Trial (SELECT). That is the real problem. SELECT was a very large clinical study that attempted to determine whether vitamin E, alone or in combination with selenium, could prevent prostate cancer. Previous studies had shown 50 IU of vitamin E was protective against prostate cancer, but SELECT researchers chose to use 400 IU of synthetic vitamin E (dl-α-tocopherol). Results showed that the subjects taking vitamin E alone had a 17% higher risk of prostate cancer compared to the control group. In the new analysis, researchers measured the levels of fats in the blood (plasma phospholipids) and concluded that men with the highest concentrations of omega-3 fatty acids including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)— derived from fish and fish oil supplements—had an increased risk of prostate cancer. Specifically, they reported a 71% increased risk of high-grade prostate cancer; a 44% increase in the risk of low-grade prostate cancer; and an overall 43% increase in risk for total prostate cancer in a subset of patients with the highest level of these omega-3 fatty acids.
Important Considerations of This Data Are the Following: (1) This study is not consistent with other studies (discussed below); (2) The study did not include information or documentation of fish or fish oil intake in the study group. It was not set up initially to evaluate these factors, hence its relevance is not as significant as studies designed to specifically determine the impact of omega-3 fatty acids on prostate cancer risk; (3) There is no evidence that anybody in this study took fish oil supplements or even ate fish; (4) In usual circumstances, plasma phospholipid levels of EPA and DHA reflect very recent intake and are considered a poor biomarker of long-term omega-3 intake; (5) The study did not measure plasma phospholipids on an individual basis and instead pooled data from blood samples collected at enrollment of the study; (6) Fish and fish oil ingestion produces a big rise in plasma omega-3 levels in about 4.5 hours and washes out around 48 hours; (7) The data may reflect cancer activity rather than a causative association. Without dietary history or documentation of fish oil use there is no way of knowing. Lastly, the following statement by the authors suggests that they may have significant bias: “There is really no evidence that taking dietary supplements is beneficial to health, and there is increasing evidence that taking high doses is harmful.” Such a statement shows a clear axe to grind in light of a great deal of scientific evidence on the value of dietary supplementation. A Closer Look at the Reported Results Let’s take a closer look at the reported results to see if things add up. The bottom line is that they do not. First,
Integrative Medicine • Vol. 12, No. 5 • October 2013
82 P value DHA <2.46 . Keep in mind that even in the United States the average plasma level of long-chain omega-3 fatty acids is slightly above 4%.93 2.16 1.09. But.37 1.00 1.007 1. But.15 1.09 1.22 .08 1. however.43 0. What this means is that there may be increased conversion of EPA to DHA in prostate cancer.009 1.00 0. What Do Other Studies Show? In addition to population-based studies.28 1.43 . there was statistical significance. so no real conclusions can be made.52 Total Cancer (834 pts) 3. For example.91 1.00 1. as it was probably a random finding. prostate cancer incidence and death rates are among the lowest known in populations consuming the traditional Japanese or Mediterranean diets.78 1.00 0. the levels reported here are lower than normal and the ratio of EPA to DHA is also a little lower as well.05 to be deemed anything more than random chance). the level of EPA was lower than that typically found and the ratio of EPA to DHA was also lower. To share or copy this article. What the researchers did next was divide up cancer patients by their blood levels of fatty acids and look at the hazard ratio—the relative risk over time—associated with different levels of the various fatty acids (see Table 2). Associations Between EPA and DHA Among SELECT Participants by Prostate Cancer Grade (N = 2273) Long-chain omega-3 fatty acids (% of total fatty acids) EPA <0.66 High-grade Cancer (156 pts) 3. one interesting observation is Murray—SELECT that the hazard ratio (HR) actually went down in highgrade prostate cancer in the group with the highest level of DHA compared to the next highest group.06 0. please visit copyright. So.31 >5.82 >0. the levels are quite similar among the groups. As Table 1 shows.58-0.26 1.31 P value Total Low-grade High-grade Total Cancer Low-grade High–grade Cancer Cancer Cancer Hazard Ratio Hazard Ratio Hazard Ratio (834 pts) (684 pts) (156 pts) 183 176 231 244 193 192 212 237 176 196 217 245 146 140 198 200 159 154 174 197 146 159 176 203 33 39 37 47 29 36 49 42 26 35 52 43 1.24 1.68-4. No. For DHA.18 . These blood levels of EPA+DHA are actually quite modest and do not reflect high levels of fish or fish supplements being consumed. As it relates to EPA.71 .74 Total EPA+DHA (% of total fatty acids) Table 2.00 1.com Table 1.39 1.42-5. if it were that the higher the level the higher the HR.33 2.008 1.01 1.66 Low-grade Cancer (684 pts) 3. this finding has a P value of . statistical significance was not achieved for total cancer or high-grade cancer (the P value has to be less than . The average EPA+DHA plasma level for men in the United States is generally approximately 4%. then aggressive prostate cancer would be a major health concern and the leading cause of death in any country with even moderate fish consumption. If that were true.04-3.41 4. again. Distribution of EPA and DHA Among SELECT Participants by Prostate Cancer Grade (N = 2273) No Cancer (1364 pts) 3.57 0. several studies have been conducted that were actually designed to Integrative Medicine • Vol.30 .00 1. To subscribe. 5 • October 2013 19 . 12.87 1.009 1. A key point is that neither group showed a high level of EPA+DHA.02 consider the blood levels of EPA+DHA—the major forms of long-chain omega-3 fatty acids found in fish oil supplements. two diets with a relatively high content of EPA+DHA.38 1.62 >3.This article is protected by copyright.43-0. The facts are that population-based studies show just the opposite effect.44 .00 1.05 1.33-2.com.62 P value Total EPA+DPA+DHA <3. visit imjournal. This suggests that it is not as significant of a factor as one would expect.91 1.68 3.26 1.93 1.42 .10 1.28 1.00 1.68%.48 1. However. Use ISSN#1945-7081. the levels of DHA are typical of what is found in men consuming modest amounts of fish.39 . The authors conclude that men are at higher risk of aggressive prostate cancer if the total plasma level of longchain omega-3 fatty acids (EPA+DPA+DHA) is greater than 3.00 1.
5 • October 2013 sense for men to be consuming 1000 mg of EPA+DHA daily for general health. Leitzmann MF. while fish consumption did not affect prostate cancer incidence. 1999. 12. Wheeler DC. To subscribe. Augustsson K. EPA+DHA intake at the highest levels was associated with a 26% reduced risk of developing prostate cancer. a study spanning 22 years. 88(5):1297-1303. Cancer Epidemiol Biomarkers Prev. Am J Clin Nutr. Some fish (and fish oil supplements) can contain environmental chemicals that can contribute to prostate cancer. Arribas GL. (5) In a study of 47 866 US men aged 40 to 75 years with no cancer history in 1986 who were followed for 14 years.to three-fold increase in the risk of developing prostate cancer compared with those who consumed large amounts of fish in their diet3. and other toxic chemicals. References 1. 8.80(1):204-216. Michaud DS. Wolk A. regular ingestion of fried fish was associated with a 32% increased risk for prostate cancer.com. Am J Clin Nutr .] 2. Prostate. Mucci LA. 9. In a detailed meta-analysis conducted in 2010. 2005. Norrish AE. (2) Data from the Physician’s Health Study.98(1):104-113. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Loeb S. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT Trial. the dosage should be increased to 3000 mg of EPA+DHA daily.10 These are important considerations. et al. 4. Terry P. When ascertaining the benefits of fish consumption it is important to find out how the fish is being prepared. Fish consumption and prostate cancer risk: a review and meta-analysis. 10. 2003.92(5):1223-1233. To share or copy this article. Lancet. Mullins JK. 6. Stampfer MJ. 2012. Ma J. others do not. found that fish consumption (≥5 ×/wk) reduced the risk of dying from prostate cancer by 36%4.This article is protected by copyright.357(9270):1764-1766. J National Cancer Inst Online. Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study. Final Comments The best thing about this study is that it will stimulate more research into the role of omega-3 fatty acids in prostate health. The worst thing about this study is that it may lead to many men abandoning the use of fish oil supplements. [Epub ahead of print. 7. 3.2 A meta-analysis examines all previously conducted studies. Ritchie JM. For example. Murray—SELECT . Comparison of proposed frameworks for grouping polychlorinated biphenyl congener data applied to a case-control pilot study of prostate cancer. Chavarro JE.8 In addition.12(1):64-67. Jackson RT. Feychting M. (3) A study conducted by the Harvard School of Public Health that involved 47 882 men over 12 years found that eating fish more than three times per week reduced the risk of prostate cancer but had an even greater impact on the risk of metastatic prostate cancer. (4) In one of the best-designed studies. Song X. No. Stott-Miller M.9. Vial SL. Based upon a large amount of clinical data it makes 20 Integrative Medicine • Vol. 2001. Stampfer MJ. Consumption of deep-fried foods and risk of prostate cancer. Results showed that men who ate no fish had a two. 5. Michaud DS. Ahlbom A. For each additional 500 mg of marine fat consumed. please visit copyright. Fuortes LJ. visit imjournal. Szymanski KM. heavy metals. Lichtenstein P. Fatty fish consumption and risk of prostate cancer. et al. Hall MN. et al. it was associated with a 63% reduced mortality due to prostate cancer. Neuhouser ML. 2004 Jul. Environ Res. Stanford JL. 2013. Brasky TM. Skeaff CM. Darke AK. 2013 July 2010. Sesso HD.com determine the effects of fish and fish oil consumption in prostate cancer. researchers in New Zealand examined the relationship between prostate cancer risk and EPA+DHA in red blood cells (a more accurate marker for long-term omega-3 fatty acid intake). 2008. et al. Urol Oncol. Br J Cancer. Am J Clin Nutr.7 While some studies make an important distinction.73(9):960-969. Environmental exposures and prostate cancer. A prospective study of intake of fish and marine fatty acids and prostate cancer. 2010. Higher levels of EPA+DHA were associated with a 40% reduced risk of prostate cancer6. such as polychlorinated biphenyls (PCBs). And. the risk of metastatic disease decreased by 24%5. many studies do not control for the quality of fish or fish oil. Rimm EB. Sharpe SJ.81(7):1238-1242. Use ISSN#1945-7081.30(2):216-219. Here are results from some of these studies: (1) Researchers investigated the effect of dietary fatty fish intake among 6272 Swedish men who were followed for 30 years. if they are suffering from one of the over 60 different health conditions shown to be benefitted by fish oil supplementation. A 22-y prospective study of fish intake in relation to prostate cancer incidence and mortality.
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