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Omega-3s Linked, Weakly, to Rare Prostate Cancer
4/28/2011
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A new study seems to link omega-3s to a rare form of prostate cancer ... but that link is both statistically weak and biologically implausible.
 
This “case-control” epidemiological study came to some unexpected, inexplicable findings, which have been reported uncritically and widely mischaracterized.
 
Study participants who'd developed a rare, aggressive, “high-grade” form of prostate cancer over a seven year period had slightly higher blood levels of omega-3s, compared with healthy controls.
 
However, higher omega-3 blood levels were not linked to increased risk of the far more common, slow-growing kind of prostate cancer called “low-grade”.
 
Link between omega-3s and “high-grade” prostate cancer appears very weak
We received some cogent comments from biochemist Doug Bibus, Ph.D., an expert in testing blood for omega-3s and other fatty acids. We’ve paraphrased his critique here:
  • The authors did not control for, or document the men’s recent omega-3 intakes, which can significantly affect blood levels. This flaw casts major doubt on the ability to draw reliable conclusions. 
  • Only 125 participants out 3,461 men were diagnosed with “high-grade” prostate cancer during the seven-year trial … a number barely large enough to allow a statistically significant correlation. 
  • The difference in average DHA blood levels between the healthy controls and the 125 men with “high-grade” prostate cancer was only 0.15%. The cancer cases had 2.99% omega-3 DHA in their blood cell membranes, versus 2.84% in the healthy controls.
  • The tiny difference in the DHA blood levels between healthy controls and the participants with “high-grade” prostate cancer seems very unlikely to have an impact on the development of prostatic cancer. Instead, it is more likely due to greater consumption of fish or fish oil among the patients with “high-grade” prostate cancer. 
  • To put these percentages into perspective, DHA blood levels range from 2-10 percent red blood cell membrane fatty acids in people with low to high intakes of omega-3s.
And most news reports highlighted a misleading statistic ... that the participants with the highest blood levels of omega-3s were two-and-a-half-times more likely to have developed rare, “high-grade” prostate cancer.
 
But a closer look reveals that the difference in omega-3 DHA blood levels between the men who developed “high-grade” prostate cancer   a mere 0.15%   was so small as to be virtually meaningless.
 
For more on the study's weaknesses  which render the headlines on most media reports highly misleading  see our sidebar “Link between omega-3s and 'high-grade' prostate cancer appears very weak”.
 
And, as lead author Theodore M. Brasky, Ph.D., said, “Overall, the beneficial effects of eating fish to prevent heart disease outweigh any harm related to prostate cancer risk.” (FHCC 2011)
 
Prior studies examining links between omega-3 intake and prostate cancer have generally associated higher omega-3 intake with reduced risk.
 
For example, a smaller case-control study found that the men with the highest intakes were 63 percent less likely to develop aggressive, “high-grade prostate cancer, compared to men with the lowest omega-3 intakes. (See “Omega-3s May Boost Prostate Health for Some Men”. 
 
We should note that unlike the new study, which used blood tests to accurately gauge blood levels, the earlier one could only estimate men’s omega-3 intakes, based on their reported fish and fish oil intake.
 
However, there is additional epidemiological evidence that omega-3s may deter prostate cancer: see “Prostate/Colon Risks Raised by High Omega-6/Omega-3 Ratio” and “Fish and Omega-3s Linked to Prostate Health ... Again”.)
 
Study sought to test assumptions about inflammation, cancer, and dietary fats
The researchers behind the new study, from Seattle’s Fred Hutchinson Cancer Research Center, noted that chronic inflammation is known to increase the risk of several cancers.
 
They observed that the body uses long-chain omega-3 fatty acids – the omega-3 EPA and DHA found in our cell membranes and in fish and fish oils – to moderate or resolve inflammation.
 
In contrast, the omega-6 fats that predominate in most vegetable oils – except olive, canola, macadamia, and hi-oleic sunflower oils – tend to promote or prolong inflammation.
 
(This is also true of the pre-inflammatory “trans” omega-6 fats found in partially hydrogenated oils, which are being gradually removed from packaged and fast foods.)
 
As Dr. Brasky said, “… we thought that omega-3 fatty acids would reduce and omega-6 and trans-fatty acids would increase prostate cancer risk.”
 
But the result of the analysis defied expectations by linking higher omega-3 intake from fish to increased risk of an uncommon, fast-moving kind of prostate cancer.
 
Findings link omega-3s to higher risk of uncommon, “high-grade” prostate cancer
Researchers at the Fred Hutchinson Cancer Research Center analyzed data from a seven-year clinical trial involving 3,461 men aged 55 to 84, called the Prostate Cancer Prevention Trial.
 
Among the trial participants, very few took fish oil supplements, and the great majority got omega 3s only from eating fish.
 
After analyzing diet and health records from the participants, Brasky’s team uncovered several counterintuitive correlations:
  • Men with the highest blood levels of omega-3 DHA had two-and-a-half-times the risk of developing aggressive, uncommon “high-grade” prostate cancer, compared to men with the lowest DHA levels.
  • Omega-3s did not raise the risk of commonplace, “low-grade”, slow-growing prostate cancer.
  • Men with the highest blood ratios of trans fats were 50 percent less likely to have high-grade prostate cancer, and trans fat intake had no link to low-grade prostate cancer.
  • Omega-6 fats were not linked to a higher or lower risk of either kind of prostate cancer.
As Dr. Brasky said, “We were stunned to see these results and we spent a lot of time making sure the analyses were correct.” (FHCC 2011)
 
“Our findings turn what we know – or rather what we think we know – about diet, inflammation and the development of prostate cancer on its head and shine a light on the complexity of studying the association between nutrition and the risk of various chronic diseases.” (FHCC 2011)
 
The Hutchinson team says that any mechanisms behind the apparent – but unproven by this study – capacity of omega-3s to raise the risk of high-grade prostate cancer remain unknown.
 
As Brasky said, “Besides inflammation, omega-3 fats affect other biologic processes. It may be that these mechanisms play a greater role in the development of certain prostate cancers.” (FHCC 2011)
 
 
Sources
  • Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, Thompson IM, King IB, Albanes D, Kristal AR. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial. Am J Epidemiol. 2011 Apr 24. [Epub ahead of print]
  • Fred Hutchinson Cancer Research Center  (FHCC). High percentage of omega-3s in the blood may boost risk of aggressive prostate cancer. April 25, 2011. Accessed at
  • http://www.eurekalert.org/pub_releases/2011-04/fhcr-hpo042511.php
 
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