During the summer of 2013, the omega-3 industry began defending itself from a barrage of criticism, stimulated by the publication of 'Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial', which concluded that higher omega-3 fatty acid levels are associated with an increased risk of prostate cancer.1
In the absence of the authors’ over-extrapolation of the data, unsubstantiated conclusions and comments reached the media that went beyond the study’s design; the results per se wouldn’t have been an issue. Although scientists are obligated to propose an explanation for their results, it was irresponsible of them to mislead the public by creating a media circus. In this case, correlation became causation in the media — an impossibility, given the research conducted.
Fast forward 14 months and the scientific evidence has changed significantly. A new meta-analysis examining the associations between the concentrations of circulating fatty acids, including omega-3s, and subsequent risk of prostate cancer in a reanalysis of individual participant data from seven prospective studies was published by a group of scientists, including two of the co-authors of the infamous summer 2013 article2, Drs Theodore Brasky and Alan Kristal. In contrast to the 2013 publication, this one is appropriately tempered and was not accompanied by an author-stimulated media frenzy.
There remains no plausible biological mechanism for omega-3 prostate cancer tumourigenesis
And whereas the results demonstrated that men with higher circulating EPA levels had a slightly elevated risk of developing total prostate cancer, a cause and effect relationship was not established. In addition, there remains no plausible biological mechanism for omega-3 prostate cancer tumourigenesis. The authors even admitted the difficulty in drawing any conclusions about EPA from the analysis and concluded: 'There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk.'
The most recent results are decidedly different from the 2013 publication, which indicated that men in the highest long-chain omega-3 quartile had increased risks of low-grade, high-grade and total prostate cancer compared with men in the lowest quartiles. In the present article, no associations were reported between omega-3s and aggressive or high-grade tumours. Only EPA was associated with a slightly elevated risk of developing total prostate cancer, a finding that could have been influenced by study heterogeneity (variability or differences between studies) or detection bias, which refers to systematic differences between groups in how outcomes are determined. For example, in the current meta-analyis, there were differences in when the prostate cancer was diagnosed (higher risk in cancers diagnosed after 2000 than in earlier cancers).
Only EPA was associated with a slightly elevated risk of developing total prostate cancer, a finding that could have been influenced by study heterogeneity or detection bias
Although the dataset used in the most recent meta-analysis was similar to that used in the meta-analysis portion of the first paper, individual participant data was required and the authors were unable to obtain the data from two of the sources. However, two additional data sources were added to this study and it appears that their inclusion changed the results.
Also, whereas the new paper provided a little clarity in a number of areas, one area of uncertainty was not addressed. In the first paper, the differences between the lowest and highest quantiles of EPA and DHA levels were minor — so low in fact that it was unlikely to be related to significant differences in consumption patterns. However, this new study did not provide any insight into how large the differences in EPA and DHA status were between quantiles. If the differences were larger than the first study, it would help to provide further evidence for why there were fewer associations in the current paper.
The EFSA Addendum
One week following the release of this most recent publication, the European Food Safety Authority (EFSA) published an opinion that included a thorough review of the scientific evidence for an association between EPA and DHA, individually and combined, and the risk of prostate cancer.3 The conclusion was that 'on the basis of available data, there is no evidence for a role of EPA and/or DHA intake in the development of prostate cancer'.
While regulators in the EU can turn to EFSA to conduct rigorous scientific reviews, not every country has a similar scientific body
EFSA’s opinion is significant for a couple of reasons. First, the Commission’s request to review the scientific evidence was stimulated initially by questions from Members of the European Parliament (MEPs), which resulted in a question from a Member State. This suggests that the media, not science, can drive government decisions. While regulators in the EU can turn to EFSA to conduct rigorous scientific reviews, not every country has a similar scientific body. This could have dangerous public health implications, such as the rescission of omega-3 intake recommendations in the face of public pressure, rather than scientific reality.
Second, this is the most thorough review of the body of scientific evidence completed to date. Rather than just look at one type of study in human populations, it examined the entire literature base. EFSA noted that there was 'no evidence from prospective cohort studies for an association between EPA and/or DHA intake and the incidence of prostate cancer' and that the various case-control studies on biomarkers needed to be discounted because blood levels of EPA and DHA do not correlate well with actual intakes.
This most recent meta-analysis should have reversed, at least in part, the damage done to consumer confidence
This opinion comes almost two years after EFSA concluded that 'supplemental intake of EPA and DHA combined at doses of up to 5g/day does not give rise to safety concerns for adults'.4 This new assessment further strengthens that conclusion because the original assessment did not consider prostate cancer risk. We can now add yet another area of risk to the list of reasons why EPA and DHA intakes are safe. This most recent meta-analysis, in addition to the EFSA opinion, should have reversed, at least in part, the damage done to consumer confidence regarding EPA and DHA by the 2013 publication. Owing to a lack of media coverage, however, they appear to have had no impact.
References
1. T.M. Brasky, et al., “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial,” J. Natl Cancer Inst. 105, 1132–1141 (2013).
2. Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group, “Circulating Fatty Acids and Prostate Cancer Risk: Individual Participant Meta-Analysis of Prospective Studies,” J. Natl Cancer Inst. 106(9): doi: 10.1093/jnci/dju240 (2014).
3. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), “Scientific Opinion on the Extension of Use for DHA and EPA-Rich Algal Oil from Schizochytrium sp. as a Novel Food Ingredient,” EFSA Journal 12(10): doi:10.2903/j.efsa.2014.3843 (2014).
4. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), “Scientific Opinion on the Tolerable Upper Intake Level of Eicosapentaenoic Acid (EPA), Docosahexaenoicacid (DHA) and Docosapentaenoic Acid (DPA),” EFSA Journal 10(7): doi:10.2903/j.efsa.2012.2815 (2012).