Link Between Omega-3 Fatty Acids and Increased Prostate Cancer Risk Confirmed

Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk: 

Alan Kristal

Senior author Alan Kristal, Dr.P.H., is a member of the Public Health Sciences Division at Fred Hutch.

A second large, prospective study by scientists at Fred Hutchinson Cancer Research Center has confirmed the link between high blood concentrations of omega-3 fatty acids and an increased risk of prostate cancer.

Published in the online edition of the Journal of the National Cancer Institute, the latest findings indicate that high concentrations of EPA, DPA and DHA – the three anti-inflammatory and metabolically related fatty acids derived from fatty fish and fish-oil supplements – are associated with a 71 percent increased risk of high-grade prostate cancer. The study also found a 44 percent increase in the risk of low-grade prostate cancer and an overall 43 percent increase in risk for all prostate cancers.

The increase in risk for high-grade prostate cancer is important because those tumors are more likely to be fatal.

The findings confirm a 2011 study published by the same Fred Hutch scientific team that reported a similar link between high blood concentrations of DHA and a more than doubling of the risk for developing high-grade prostate cancer. The latest study also confirms results from a large European study.

“The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis and recommendations to increase long-chain omega-3 fatty acid intake, in particular through supplementation, should consider its potential risks,” the authors wrote.

“We’ve shown once again that use of nutritional supplements may be harmful,” said Alan Kristal, Dr.P.H., the paper’s senior author and member of the Fred Hutch Public Health Sciences Division. Kristal also noted a recent analysis published in the Journal of the American Medical Association that questioned the benefit of omega-3 supplementation for cardiovascular diseases. The analysis, which combined the data from 20 studies, found no reduction in all-cause mortality, heart attacks or strokes.

Theodore Brasky

Corresponding author Theodore Brasky, Ph.D., a research assistant professor at The Ohio State University Comprehensive Cancer Center, was a postdoctoral trainee at Fred Hutch when the research was conducted.

“What’s important is that we have been able to replicate our findings from 2011 and we have confirmed that marine omega-3 fatty acids play a role in prostate cancer occurrence,” said corresponding author Theodore Brasky, Ph.D., a research assistant professor at The Ohio State University Comprehensive Cancer Center who was a postdoctoral trainee at Fred Hutch when the research was conducted. “It’s important to note, however, that these results do not address the question of whether omega-3’s play a detrimental role in prostate cancer prognosis,” he said.

Kristal said the findings in both Fred Hutch studies were surprising because omega-3 fatty acids are believed to have a host of positive health effects based on their anti-inflammatory properties. Inflammation plays a role in the development and growth of many cancers.

It is unclear from this study why high levels of omega-3 fatty acids would increase prostate cancer risk, according to the authors, however the replication of this finding in two large studies indicates the need for further research into possible mechanisms. One potentially harmful effect of omega-3 fatty acids is their conversion into compounds that can cause damage to cells and DNA, and their role in immunosuppression. Whether these effects impact cancer risk is not known.

The difference in blood concentrations of omega-3 fatty acids between the lowest and highest risk groups was about 2.5 percentage points  (3.2 percent vs. 5.7 percent), which is somewhat larger than the effect of eating salmon twice a week, Kristal said.

The current study analyzed data and specimens collected from men who participated in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a large randomized, placebo-controlled trial to test whether selenium and vitamin E, either alone or combined, reduced prostate cancer risk. That study showed no benefit from selenium intake and an increase in prostate cancers in men who took vitamin E.

The group included in this analysis consisted of 834 men who had been diagnosed with incident, primary prostate cancers (156 were high-grade cancer) along with a comparison group of 1,393 men selected randomly from the 35,500 participants in SELECT.

The National Cancer Institute and the National Center for Complementary and Alternative Medicine funded the research.

Also participating in the study were additional Fred Hutch scientists and researchers from the University of Texas, University of California, University of Washington, National Cancer Institute and the Cleveland Clinic.

 Fish oil linked to prostate cancer. NBC’s Dr. Nancy Snyderman reports.

 

References

Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA, Kristal AR. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J Natl Cancer Inst 2013 Jul 10. [Epub ahead of print]

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; 173: 1429-39.

Council for Responsible Nutrition. CRN Says New Study on Omega-3 Conclusions Are Overblown. Press Release, July 11, 2013.

 

Why fish is so good for you

Scientists of Friedrich Schiller University Jena and Jena University Hospital decode the antihypertensive impact of omega-3 fatty acids.

Scientists of Jena University and Jena University Hospital now analyzed the impact of omega-3 fatty acids and described the underlying molecular mechanisms for the first time.

Scientists of Jena University and Jena University Hospital now analyzed the impact of omega-3 fatty acids and described the underlying molecular mechanisms for the first time.

Fish is healthy: easy to digest and with a high level of precious proteins, fish is considered an important part of a healthy diet. And with the so-called omega-3 fatty acids fish contains real ‘fountains of youth’. These fatty acids – like docosahexaeonic acid (DHA) occur mostly in fatty fish like herring, salmon and mackerel. They are thought to lower the blood pressure, to strengthen the immune system and to have positive effects on the development on the nervous system and the cardiovascular system.

“Clinical studies about the intake of nutritional supplements containing omega-3 fatty acids haven’t provided complete clarity so far,” Prof. Dr. Stefan H. Heinemann from Friedrich Schiller University Jena (Germany) says. “The molecular impact of the omega-3 fatty acids isn’t fully understood yet,” the biophysicist continues. But now scientists of the DFG research group FOR 1738 based at Jena University are able to bring new facts to light: in two newly published articles for the well-known science magazine ‘Proceedings of the National Academy of Sciences, USA’ they describe how they analyzed the impact of omega-3 fatty acids on a systemic level and they also described the underlying molecular mechanisms for the first time.

The teams around Prof. Heinemann (Jena University), Prof. Dr. Michael Bauer (Jena University Hospital) and Prof. Dr. Toshinori Hoshi (University of Pennsylvania) were able to show that the so-called ‘SLO1′ potassium channel is an important component in the effectiveness of omega-3 fatty acids. “These ionic channels act like very specific receptors for DHA and are opened by the binding of the omega-3 fatty acids,” Biophysicist Heinemann explains. In the case of other omega-3 fatty acids – like the shorter eicosapentaenoic acid (EPA) or the alpha-linolenic acid (ALA) extracted from plants – the impact is much weaker.

Prof. Bauer and his colleagues examined the effects of omega-3 fatty acids on SLO1 channels of the cardiovascular system by experimenting with mice. “Administration of DHA should result in an expansion of the blood vessels and consequently a drop in blood pressure,” the physician says. The laboratory experiments confirmed exactly that. In genetically modified mice however, which were not able to produce the SLO1 channel, the antihypertensive impact of DHA failed to appear. “Thus we were able to show for the first time that DHA directly influences the blood pressure, which is being mediated through SLO1 channels,” Bauer summarizes.

Beyond that, the scientists made another surprising discovery: a variant of DHA, which can often be found in nutritional supplements containing omega-3 fatty acids, doesn’t show an antihypertensive effect. Moreover, it suppresses and even diminishes the effect of the natural DHA from fish oil. “The intake of non-natural omega-3 fatty acids can therefore also have counter-productive effects,” Prof. Bauer stresses. This is of particular importance for the nutritional supplements of patients in intensive care who are being drip-fed: their supplements of omega-3 fatty acids should be specifically aimed at and adapted to the patients’ clinical requirements.

 

References

Hoshi T, Wissuwa B, Tian T, Tajima N, Xu R, Bauer M, Heinemann SH, Hou S (2013) Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channelsProceedings of the National Academy of Sciences USA (DOI: 10.1073/pnas.1221997110)

Hoshi T, Tian T, Xu R, Heinemann SH, Hou S (2013) Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHAProceedings of the National Academy of Sciences USA (DOI: 10.1073/pnas.1222003110)