A recently published epidemiological study reported that higher concentrations of long-chain omega-3 polyunsaturated fatty acids (PUFAs) in plasma phospholipids are associated with an increased risk of prostate cancer [J Natl Cancer Inst. 2013 Jul 10 (Epub ahead of print)]. Plasma phospholipids reflect usual mid- to long-term dietary intake of fatty acids in healthy individuals and are used as a biomarker of intake in lieu of dietary assessment methodology. Marine fish and fish oil supplements are rich sources of long-chain omega-3 PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
The current study identified 834 cases of prostate cancer from a larger study of 35,533 male participants in the Selenium and Vitamin E Cancer Prevention Trial (SELECT); 1,393 age- and race-matched controls were randomly selected for comparative purposes. Plasma samples that were collected at baseline were used to measure prostate-specific antigen (PSA) and the amounts of long-chain omega-3 PUFAs present in plasma phospholipids.
The authors used these cases and controls to calculate the likelihood of developing prostate cancer depending on one’s plasma long-chain omega-3 PUFA concentration. Compared with men with the lowest levels of plasma omega-3 PUFA, men with the highest levels had about a 45% increased risk of developing low-grade or total (any grade) prostate cancer. The authors and news outlets also highlighted a purported 70% increased risk of high-grade prostate cancer, but looking at the original data indicates that this finding was not statistically significant.
While the results of this study contribute to a body of evidence that reports on the association between omega-3 PUFAs and prostate cancer risk, it neither tested nor determined whether high intake of omega-3 PUFAs causes prostate cancer. In other words, this study, which was a so-called “observational” study, only looked at associations between omega-3 PUFAs and prostate cancer, but it cannot establish cause-and-effect relationships. Three other observational studies have variably reported an increased risk [Am J Epidemiol 2011;173:1429-39], a reduced risk [Cancer Epi Biomarkers Prev 2007;16:1364-70], or no association [Cancer Causes Control 2009;20:211-23] of prostate cancer with different blood measures of total omega-3 PUFAs. Furthermore, while the total plasma levels of omega-3 PUFAs in the current study were significantly different between the cases and controls, the magnitude of the difference is likely too small to have any meaningful biological effect on prostate cells or any other cells in the body.
The authors did not offer a plausible explanation why omega-3 PUFA content in blood might be associated with an increased risk of prostate cancer. It could be speculated that an unidentified factor associated with plasma omega-3 PUFAs may be affecting the prostate, or perhaps omega-3 PUFA metabolism is altered during prostate carcinogenesis and thus creating an altered plasma fatty acid profile. The latter would be a case of “reverse causation,” meaning that prostate carcinogenesis would be the cause, rather than the consequence, of altered plasma omega-3 PUFAs. These hypotheses, among others, would have to be tested in a more rigorous type of study design.
In sharp contrast to the current study, a 2010 systematic review and meta-analysis that pooled and analyzed the results of several epidemiological studies [Am J Clin Nutr 2010;92:1223-33] found no association between fish consumption and prostate cancer risk (14 studies), while high consumption of fish was associated with a 63% reduction in prostate cancer-specific mortality (4 studies).
Omega-3 PUFAs are known to have several beneficial health effects, particularly on cardiovascular health (see the LPI’s response to a recent review on omega-3 PUFAs and CVD risk). For healthy adults, the LPI continues to recommend regular consumption of fish or a two-gram fish oil supplement several times per week (see the LPI Rx for Health).