Fish Oil Increases Risk of Prostate Cancer?

A new study has been making its rounds online that suggests a connection between omega-3 fats and prostate cancer risk. Since fish oil is an enriched source of omega-3 fats, many have taken this study to mean that fish oil causes prostate cancer. Is this true, or possibly just another case of the research literature being sensationalized in the popular media in a grab for headlines? Let us examine.

The study in question is one that appears to be a study based off of the SELECT trials (a large trial initially investigating the link between vitamin E and selenium with prostate cancer) which initially did not find a protective effect of supplementation on prostate cancer, but say an increased risk associated with vitamin E occurred during prolonged follow-up. This led to the current study.

A new study found that fish oil supplementation is associated with increased risk for increased prostate cancer. The study was a observational, and used participants from a previous large scale intervention called SELECT.

Lets Look at the Study

This will get science-heavy. If it's too heavy for you, just skip to the next section.

In short, this study initially looked at participants of the SELECT trial and got a sample of persons who were diagnosed with prostate cancer (n=834) and made note of how many had advanced cancer (n=156), then 1393 persons from the SELECT study who did not have prostate cancer were selected for comparison. The researchers then measured serum omega-3 fatty acids (EPA, DHA, and their intermediate DPA) and stratified the groups into quartiles to see if there was an association.

The results showed that persons who had prostate cancer were more likely to have higher circulating omega-3 fatty acid levels (excluding ALA, which was not associated) and that omega-6 was unrelated to prostate cancer. Trans fatty acids were mostly unrelated aside from a possible positive relationship with the 16:1 trans-fatty acids 16:1n9 and 16:1n7t. When comparing the quartiles against one another (the lowest quartile being set at hazard ratio (HR) 1.00 as a reference), the highest levels of fish based omega-3 fatty acids (collectively) were associated with increased risk as assessed by Hazard Ratio (HR) for total HR = 1.23 (95% confidence interval (CI) = 1.07-1.40), low-grade HR = 1.24 (95% CI = 1.07-1.43), and high grade HR = 1.24 (95% CI = 1.00-1.54) prostate cancer. While DHA had an HR showing an association with total HR = 1.21 (95% CI = 1.07-1.37), low grade HR = 1.21 (95% CI = 1.06-1.38), and high grade HR = 1.26 (95% CI = 1.03-1.54) prostate cancer, DPA was only associated with total HR = 1.23 (95% CI = 1.03-1.46) and low grade HR = 1.30 (95% CI = 1.08-1.57) while EPA was not significantly associated with an increased risk. Alpha-linolenic acid, omega-6 fatty acids, and trans fatty acids were not correlated with cancer risk.

Note: The above risks are reported as hazard ratios along with 95% confidence intervals (CI). Hazard ratios above 1.00 (with associated 95% CIs indicating the same) mean that there is evidence for increased risk with 95% confidence that the measured value (HR) represents the true value. (for the statisticians out there, 5% Type I (alpha) error probability).

When adjusting omega-3 for omega-6 fats, it seems that the HRs for total HR =1.16 (95% CI = 0.98-1.36) and low grade HR = 1.15 (95% CI = 0.97-1.36) prostate cancer became nonsignificant while there was still a significant relation with high grade prostate cancer (HR = 1.40; 95% CI = 1.03-1.92). Media sources were reporting ~40% increases in prostate cancer overall based on the hazard ratio for total n=3 PUFAs (EPA + DHA + DPA), which was 1.43 (which equals a 4#% increased cancer risk.

Taking all omega 3 fatty acids into account (EPA + DHA + DPA), the researchers found a 43% increased prostate cancer risk.

The variables that were made note of in the analysis were education, history of diabetes, family history of prostate cancer, and SELECT intervention assignment (so, placebo or vitamin E groups). So despite the increased risk seen with vitamin E previously in SELECT it likely does not influence the results.

This study found that, when comparing the lowest 25% of subjects (assessed by how much fish oil was in their blood) against the highest 25% that the higher group had a higher frequency of prostate cancer. There was no supplemental intervention.

What Should I Know?

"Fish oil causes cancer" is a strong statement that is not appropriate to make at this point, because the present study was not designed to examine whether fish oil causes cancer nor did it look into fish oil intake at all. To be fair, this claim was not made in the study or by the authors of the study, but was made throughout the popular media. This work only examined blood omega 3 levels without respect to fish oil supplementation or even fish consumption. Thus, the question of whether fish oil has a positive or negative effect on prostate cancer is not answered by this research. Taking the present study at face value, increased blood omega-3 fats are associated with increased cancer risk. Although other work has come to similar conclusions, it is important to point out that others have not. As an example one earlier study found a reduction in prostate cancer risk with increased consumption of omega-3 fats. This nested case-control study was derived from blood collected from 14,916 healthy men in 1982. Blood samples were analyzed for fatty acid levels from 476 of these men that were diagnosed with prostate cancer in comparison to age-matched matched controls. Blood levels of omega 3 fats were inversely related to overall prostate cancer risk, with a relative risk (RR) of 0.59 (95% confidence interval = 0.38-0.93).[1]

It is important to note that neither the current study nor others like it were designed find causation. Having found an association with increased risk, it is time for researchers to develop experimental models, go back to the bench, and start testing hypotheses to look for direct causal mechanisms. As with most cancers, prostate cancer is a heterogenous disease with a number of different causes at the cellular/genetic level, some of which are not well-understood. It could be that the presence of prostate cancer in and of itself can influence omega 3 levels in the blood. Or perhaps increased omega 3 levels could interact with one or more cancer causing processes in such a way that increases cancer risk in certain people. More research is needed to answer these questions to find a causal link, if one exists.

At the most, we can state that prostate cancer is associated with increased omega-3s in the blood in a cohort of subjects in the Brasky et al (2013) study. More work is needed to establish any type of causation, and any notions that 'fish oil causes cancer' are premature and unfounded.