Omega-3 fatty acids & prostate cancer: study and stories off-base

The following is a guest blog post co-authored by Richard Hoffman, MD, MPH and by Robert Glew, PhD, both of the University of New Mexico.  Hoffman has been a story reviewer and blog contributor on this site.  Glew is an emeritus professor (and former chair) of Biochemistry and Molecular Biology at University of New Mexico.

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Very long-chain omega-3 fatty acids (O3FAs), especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been widely touted for their health benefits, particularly in preventing cardiovascular disease events and cancer in adults.  The best way to obtain these fatty acids is by eating oily marine fish (e.g., salmon, tuna, mackerel).  However, nutritional supplements have become a big business, with the consumer able to obtain these fatty acids from products such as DHA- and EPA-rich capsules containing extracted oils to O3FA-laced Raisin Bran.  However, the scientific evidence that these supplements are beneficial is scant.  At least these supplements were considered safe.  That’s why news stories* relating to a recent study warning that higher O3FA levels—and by implications, O3FA supplements–were associated with increased prostate cancer risk were disconcerting.

That study, published in July 2013 by the Journal of the National Cancer Institute, was the Selenium and Vitamin E Cancer Prevention Trial (SELECT).   SELECT investigators previously evaluated whether selenium and vitamin E supplements could prevent prostate cancer.  The answer, in a paper published in Journal of the American Medical Association, was no.  A subsequent publication by these same researchers actually suggested that men receiving just vitamin E alone were at increased risk for developing prostate cancer compared to men receiving a placebo.  In the latest report, although this was not an aim of the original study, investigators evaluated the association between blood levels of various fatty acids and risk for prostate cancer.  Since analyzing fatty acids is prohibitively expensive, these investigators elected to analyze the fatty acid composition of serum phospholipids on a subset of men whose blood had been stored.

The main finding was that men with the highest baseline blood level of long-chain O3FAs had a 43% increased risk for being diagnosed with prostate cancer compared to men with the lowest levels of these particular fatty acids—and a 71% increased risk for being diagnosed with high-grade prostate cancers.

Taken at face value, these results sound ominous.  However, a closer look at the paper raises several critical concerns regarding study design and data interpretation.  The risk associated with O3FA levels seems quite overstated.  First of all, the absolute overall risk of being diagnosed with prostate cancer was less than 5%.  Most men in the study were diagnosed based on an abnormal PSA test result, which is known to markedly increase the risk of overdiagnosis of prostate cancer–that is, finding cancers that would never cause harm during a man’s lifetime.  Overall, only 156 (18.7%) of cancers were high-grade (potentially aggressive). Furthermore, there were just 17 more high-grade cancers among men in the highest quartile of O3FA levels compared to the lowest quartile.  Even then, essentially all of these high-grade cancers were early-stage, meaning that men could still be candidates for curative therapy

Analyzing prostate cancer risk based on relative proportions of fatty acids measured in phospholipids isolated from stored serum is also problematic.  Since the measurements were obtained at baseline and could have been affected by recent meals or supplements (and the study did not attempt to distinguish the sources of O3FAs), they do not represent long-term intake before the study began–when carcinogenesis was likely occurring.  The study did not measure dietary patterns or supplement use during follow-up.  The absolute difference in DHA levels between cases and controls was only 3%, raising the question of whether such a small difference, even if statistically significant, could be biologically important—or plausible.  Indeed, ecologic data suggest a different story–populations with high dietary intake of O3FAs, particularly Alaska Natives and the Japanese, actually have very low rates of prostate cancer.

Given these important limitations, the authors’ conclusion that their findings “strongly suggest that long-chain [O3FAs] do play a role in enhancing prostate tumorigenesis” are not supported by the data.   Readers should also recognize the potential ethical and economic implications of alarming conclusions based on small statistically significant differences of dubious biological relevance.

* Examples of news stories:

• http://healthland.time.com/2013/07/11/hold-the-salmon-omega-3-fatty-acids-linked-to-higher-risk-of-cancer/
• http://well.blogs.nytimes.com/2013/07/22/omega-3s-may-raise-prostate-cancer-risk/
• http://www.foxnews.com/health/2013/07/11/omega-3-supplements-linked-to-prostate-cancer/
• http://blog.doctoroz.com/in-the-news/new-study-omega-3-acids-and-prostate-cancer
• http://www.nbcnews.com/health/fish-oils-may-raise-prostate-cancer-risks-study-confirms-6C10597283

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