The study that has precipitated these concerns about fish oils was led by Theodore Brasky, PhD of the Fred Hutchinson Cancer Research Center in Seattle, USA and published in the Journal of the National Cancer Institute.
The study was a prospective case-control study that involved comparing the blood levels of various fatty acids, including the long-chain omega-3 fatty acids, in a group of 834 men who developed prostate cancer (156 the high grade, aggressive form), against 1393 who did not. The subjects were all part of the SELECT (Selenium and Vitamin E Cancer Prevention) trial that aimed to evaluate the effects of vitamin E and selenium supplements on prostate cancer. As an aside, but because it evaluated the effects of supplements — and bearing in mind the fish oils study most certainly didn't involve studying supplements — it’s of interest that the SELECT trial found that those who took selenium supplements alone experienced a 20% reduction in absolute risk of prostate cancer, while those who took both selenium and vitamin E benefited even more, with a 60% risk reduction. Somewhat predictably, high dose vitamin E (alpha-tocopherol) on it own, exposed study subjects to a 160% increase in absolute risk.
Ever wondered why combinations of nutrients as provided for in a healthy natural diet or in concentrated forms in supplements might be better for us than taking single, isolated nutrients — as if they were drugs?
While prostate cancer is the most prevalent cancer in men, it is essentially a disease of older men, with around 8% of American men developing it between their 50th and 70th birthdays.
In the USA, based on National Cancer Institute figures, 125 men out of each 100,000 will develop prostate cancer at some stage in their lives, with diagnosis on average occurring at age 66. Death occurs in only 23 out of 100,000 and the average age of death is 80.
For more information on prostate cancer, and the opinion of leading doctors advocating non-surgical, chemo- or radio-therapy approaches, see Peter Starr’s information-packed documentary Surviving Prostate Cancer Without Surgery, Drugs or Radiation, which we think should be essential viewing for any man over the age of 40.
Key findings of study
Firstly, the investigators did not evaluate diets or record any data on fish oil supplement intake. They compared blood levels of various fatty acids, including the omega-3s eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), between those who didn't develop cancer and those who developed low-grade and high-grade prostate cancers. They assumed that subjects with the highest blood levels were taking high-dose fish oil supplements or consuming very large amounts of oily fish.
The researchers reported that men with the highest blood levels of omega-3 fatty acids had an overall 43% increase in risk for all prostate cancer, compared with men with the lowest blood levels of omega-3s. But what really made news headlines was the researchers’ finding that the risk for high-grade, aggressive prostate cancer was 71% greater, and that for low-grade, non-aggressive prostate cancer 44% greater, than among those with low blood levels of omega-3s.
The authors indicate that data on the subject of omega-3s are conflicting, but they assert that this prospective trial now provides stronger evidence that high intakes of omega-3s might be have the capacity to promote prostate cancer, especially if taken in supplemental form, where the DHA and EPA in particular are concentrated.
ANH-USA report on study
Our colleagues at ANH-USA released an important appraisal of the study yesterday, and in particular highlighted its weaknesses and the difficulties associated with drawing the conclusions made by the authors and those subsequently published in the media.
No causal relationship between high omega-3 intake and prostate cancer was demonstrated, simply an apparent association.
Major weaknesses in the investigators' interpretation of their findings were apparent, including:
The study only measured fatty acids in blood (plasma) at baseline and then annually. This does not give any measure of long-term omega-3 fatty acid intake (more accurately measured in red blood cells)
No account was taken of the oxidation state of the omega-3 fatty acids measured. Fish oils can be ingested in their native or oxidised states. Cheap fish oil supplements, as frequently sold in pharmacies and supermarkets, are often oxidised, i.e. rancid to a greater or lesser degree. Oxidised fish oils can produce free radicals and elevated oxidative stress, which is associated with increased cancer risk. Another source of highly oxidised omega-3 fatty acids is oily fish subjected to high-temperature cooking
Owing to the link between inflammation and cancer, subjects who developed cancer would be suffering significant inflammation, and inflammatory processes were probably elevated well before tumorigenesis occurred. Higher intakes of fish oils under such conditions could induce a pro-oxidant, rather than an antioxidant, effect
What the study described as ‘high levels’ of omega-3s are not actually typical of high blood plasma omega-3 levels, when compared against the levels observed in subjects taking large doses of good-quality fish oil supplements containing highly concentrated EPA and/or DHA
No account was taken of factors that are known or emerging predictors of prostate cancer, such as hormonal markers [e.g. testosterone, insulin growth factor 1 (IGF-1), PSA glycosylation]
The process of tumour initiation (tumorigenesis) in patients who were found to have high blood levels of omega-3 fatty acids, and who subsequently went on to develop prostate cancer, may have been firmly initiated before intake levels were increased
Those with high levels of circulating omega-3 fatty acids may have had genetic defects (polymorphisms) that affected fatty acid metabolism or oxidation
There is strong evidence from a recently published systematic review that relatively high levels of one of the omega-3 fatty acids, DPA, are associated with a reduced risk of prostate cancer. Plausible mechanisms exist for this association, involving DPA's effect on inhibiting the cyclo-oxygenase (COX) pathway of inflammation. DPA is found in marine oily fish, along with EPA and DHA, but typically in smaller amounts
For most human populations, and certainly Western ones, there has been a decline in the amount of long-chain omega-3 fatty acids consumed. In addition, the ratio of short-chain omega-6 fatty acids has increased from approximately 1:1 to 10:1. These changing ratios are likely to interfere with the health protective effects of omega-3 fatty acids.
Prostate cancer expert Anthony Victor D’Amico, MD, PhD, points out that the authors failed to adjust their calculations for the main risk factors associated with prostate cancer. Key factors such as ethnicity, age, body mass index (BMI) and prostate specific antigen (PSA) level were not accounted for, despite being listed in the table of baseline patient characteristics and SELECT trial cancer outcomes (Table 1). Prof D’Amico has commented: "The study really cannot make the conclusion that it’s trying to. These types of studies are not cause and effect. These studies are simply associations...They didn't account for the known predictors of prostate cancer when they were making the calculation. You're left with a weak association”.
The contamination issue
Environmental toxins, such as polychlorinated biphenyls or methyl mercury compounds, as found in fish and in cheap, unpurified fish oil supplements, can disrupt androgen and oestrogen balance. This in itself could potentially lead to high-grade cancers, prostate cancer included. In addition, omega-3 fats can become damaged in an oxidising environment, including cases of chronic inflammation. The derivative products could then ultimately cause DNA damage leading to cancer.
Prostate cancer: changes in the metabolism of fats
Some studies have shown that prostate cancer can bring about changes in fatty acid metabolism. Fatty acid beta-oxidation appears to become a more dominant energy pathway, due to the alteration of several enzymes. Glycolysis, the glucose metabolic pathway, usually increases with most malignancies, but in prostate cancer, it appears to slow down.
A new meta-analysis by Michael E Chua, MD explains: “The presence of long chain n-3 PUFA (DHA and EPA) in the prostate cell’s beta-oxidative metabolic process leads to the formation of lipid hydroperoxides in the microenvironment of the cell; this can generate reactive species. With chronic exposure to these reactive molecules, the prostate cell can become dysplastic and develop into an aggressive cell”. Chua found that that only high serum levels of long-chain omega-3 PUFAs are associated with reduced prostate cancer risk, whilst the possible role of both EPA and DHA needs to be examined further.
Part of an orchestrated attack on natural healthcare?
Negative findings linked to the Brasky et al study have been widely reported in the media. It's been a chance to pour cold water on the public enthusiasm over supplements, in the hope the public won't even realise fish oil supplements were not even evaluated in the study.
The paper’s senior author, Dr Alan Kristal, was reported to say: “We’ve shown once again that use of nutritional supplements may be harmful”. Kristal has also drawn attention to a 2012 review published in the Journal of the American Medical Association, showing an association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events.
This attack is directed at an essential food, one with which the human race has evolved and which is solidly backed by scientific evidence. Conversely, there has been no discussion around the incidence of prostate cancers among indigenous peoples whose long-chain omega-3 fatty acid consumption is at the top end of the spectrum. The Inuit Nunangat population of Canada, for example, exhibits prostate cancer levels significantly lower than the Canadian average.
Presented along with the very negative media attention, and coming in the wake of the transatlantic attacks on supplements by Dr Paul Offit, we have to ask: is this yet another study designed to fail?
Footnote about the Fred Hutchinson Cancer Research Center
Spare the following a thought. The Hutchinson Center is a leading recipient of National Cancer Institute funding among academic and research institutions. It is ranked in the top two in National Institutes of Health funding among independent research institutions in the US. In addition, it receives funding through licensing and partnership agreements facilitated by pharmaceutical companies, e.g. Actinium Pharmaceuticals Inc. and GlaxoSmithKline. Funding is also enabled indirectly, as a result of the centre's membership of the National Comprehensive Cancer Network.
Could this have anything to do with the anti-supplement bias we've witnessed?