Do Long-chain Omega-3 Fatty Acids Increase Prostate Cancer Risk?

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by Monica Mollica

A hotly debated recent study, the SELECT trial, has casted doubt on the well documented health benefits of omega-3 fatty acids. This study found that a higher content of long-chain omega-3 fatty acids (EPA+DPA+DHA) in blood plasma was associated with a with a greater risk of low-grade (44%) and high-grade (71%) prostate cancers over a 5-year follow-up (1). Associations were similar for individual long-chain omega-3 fatty acids. Higher linoleic acid (omega-6) was associated with a 25% reduced risk of low-grade and 23% reduced risk of total prostate cancer (1) .

This has understandably generated confusion among the general public and intense discussions among health professionals and researchers. However, a deeper look at the data and study methodology reveals a different picture…
Insufficient omega-3 levels in all groups

On aspect of this study that immediately jumps off the page is that subjects in even the highest category of plasma long-chain omega-3 fatty acids were insufficiency. The omega-3 levels in this study were even lower than the levels seen with a typical non-fish and non-supplemented diet (2), and were only 40-50% of what would be expected in health conscious people taking the typical health promoting dose of fish oil (providing about 1300 mg EPA + 860 mg DHA/day) (2). The very low levels of omega-3s was even acknowledged by the study authors in the research paper, but was overlooked by the media. Note that this was not a fish oil supplement study.

Because of the large number of subjects in this study, the differences in long-chain omega-3 levels (expressed as percentages of total blood fatty acids) among the low level category without prostate cancer (4.48%) and “high” level category with prostate cancer (4.88%) did reach statistical significance. However, statistical significance and clinical (i.e. real life) significance are two different things. In studies, statistical significance (meaning that results are not caused by change) can be achieved despite minor differences in dependent variables thanks to having a large number of subjects. But when taking the subjects of out the study, the statistical significance does not translate into clinical significance when differences are small, like they were in this study (1) .

Therefore, these results have no relevance for people who eat fatty fish and/or take fish oil supplements. This is underscored by another study where supplementing a low fat diet with 5 g fish oil/day (providing a daily dose of 1000 mg EPA and 1835 mg DHA) was found to decrease prostate cancer proliferation and lower the prostate tissue omega-6:omega-3 ratio (3). A recent review paper outlining the current evidence linking polyunsaturated fatty acids with cancer risk and progression also points out that larger intakes of omega-3s may be required in order to achieve the anti-carcinogenic benefits (4).

Blood Plasma vs. Red Blood Cell Omega-3s

Another important methodological issue with this study is that it measured long-chain omega-3 fatty acids in the blood plasma fraction, as opposed to the more reliable red blood cell (RBC) fraction (5). Plasma omega-3 changes rapidly with food intake, and does not reflect long-term incorporation of omega-3 into cells and tissues. The potential measurement error can be envisioned by the fact that 24 hours after ingesting a typical fish oil dose (3.6 g), the elevation in plasma long-chain omega-3 fatty acids EPA and DHA is 10-fold greater in than that in RBCs (5). Thus, the blood plasma measurement in the SELECT trial doesn’t reflect long-term omega-3 intakes, and therefore relating such a highly fluctuating measurement to a chronic outcome like prostate cancer is absurd. It also means that an incidental fatty fish meal the previous day before the blood draw easily could have placed in the highest omega-3 level category.

Results confounded by other prostate cancer risk factors

Despite collecting data on other prostate cancer risk factors, no adjustment was made for these in the statistical models (1). For example, baseline PSA (prostate specific antigen, a blood marker of prostate disease) was higher in those who contracted prostate cancer, indicating pre-existing prostate disease.

Further, more subjects in the prostate cancer group also had first-degree relative with prostate cancer, indicating a genetic influence. This is supported by the identified strong genetic impact on the fatty acid composition in blood phospholipids (6).

Finally, blood fatty acid composition might not be the best indicator of prostate cancer risk. Another recent study showed that the omega-3 fatty acid alpha-linolenic acid (ALA) in prostate tissue, regardless of intake (and blood level), is positively associated with aggressive prostate cancer, and that this relationship may depend on genetic variation in ALA metabolism (7). This counters the finding in the notorious “long-chain omega-3 fatty acids – prostate cancer risk” study which found blood levels of ALA not to be associated with prostate cancer risk.

Evidence to the contrary

In contrast to the findings in the SELECT trial, numerous other prior studies have found higher intakes of fish oil to be associated with reduced prostate cancer incidence and deaths (8-13).

The SELECT trial is also found higher linoleic acid (omega-6) to be associated with a 25% reduced risk of low-grade and 23% reduced risk of total prostate cancer (1). This also counters previous findings that a high ratio of oomega-6 to omega-3 fat intake may increase the risk of overall prostate cancer (10).

These contradictory results in the SELECT trial, compared to many other controlled studies, further strengthen the suspicions on its methodological issues.

Bottom Line

Long-chain omega-3 fatty acids, like those found in fish oil, have well documented health promoting effects on the cardiovascular system and significantly protect against cardiovascular diseases (14-19), which remain the leading cause of morbidity and mortality in modern societies (20, 21). Even if there is a slim chance of an increased prostate cancer risk, when looking at the whole picture, for majority of men the benefits far outweigh the potential risk. Thus, daily intake of long-chain omega-3 fatty acids is still recommended for health promotion and disease prevention, even for men.

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About the Author:
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Monica Mollica
Monica Mollica has a Bachelor’s and Master’s degree in Nutrition from the University of Stockholm, Sweden, and is an ISSA Certified Personal Trainer. She works a dietary consultant, health journalist and writer for www.BrinkZone.com, and is also a web designer and videographer.

Monica has admired and been fascinated by muscular and sculptured strong athletic bodies since childhood, and discovered bodybuilding as an young teenager. Realizing the importance of nutrition for maximal results in the gym, she went for a BSc and MSc with a major in Nutrition at the University.

During her years at the University she was a regular contributor to the Swedish bodybuilding magazine BODY, and she has published the book (in Swedish) “Functional Foods for Health and Energy Balance”, and authored several book chapters in Swedish publications.

It was her insatiable thirst for knowledge and scientific research in the area of bodybuilding and health that brought her to the US. She has completed one semester at the PhD-program “Exercise, Nutrition and Preventive Health” at Baylor University Texas, at the department of Health Human Performance and Recreation, and worked as an ISSA certified personal trainer. Today, Monica is sharing her solid experience by doing dietary consultations and writing about topics related to health, fitness, bodybuilding, anti-aging and longevity.


References:

1. 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, 105:1132-1141.
2. Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY: Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem. 2006, 52:2265-2272.
3. Aronson WJ, Kobayashi N, Barnard RJ, et al.: Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy. Cancer Prev Res (Phila). 2011, 4:2062-2071.
4. Azrad M, Turgeon C, Demark-Wahnefried W: Current Evidence Linking Polyunsaturated Fatty Acids with Cancer Risk and Progression. Front Oncol. 2013, 3:224.
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