News of a study linking omega-3s to prostate cancer spread fast.
Given the study's glaring weaknesses and ample evidence to the contrary, it's premature to fear that fish fats pose any danger.
Except for rare, aggressive, “high-grade” prostate cancers, most prostate tumors are considered “low-grade”, and grow very slowly.
This explains why relatively few men die from prostate cancer, and why most men who die from it succumb at advanced ages.
Nutrition guru pokes huge holes in omega-3/prostate study
Jonny Bowden, PhD, CNS
is a best-selling authority on nutrition and health whose advice* flows from hard science and common sense ... and he has a sharp eye for pseudo-science.
Harvard prostate cancer expert calls new study “weak, at best”
Anthony D'Amico, M.D., is professor of Radiation Oncology at Harvard Medical School and chief of Genitourinary Radiation Oncology at the Brigham and Women's Hospital and Dana-Farber Cancer Institute.
He's co-authored more than 140 peer-reviewed publications on the detection and treatment of prostate cancer, and he has co-edited four urologic oncology textbooks.
In a recent radio interview about the new study, he opined that the “… scientific strength of it is weak, at best,” and explained one key reason why:
“…these types of studies are not cause and effect; that is, if you take the fish oil you're going to get an aggressive or some kind of prostate cancer … [so] you try to adjust for that association, for all the things you know can cause prostate cancer.”
“They tried this, but they didn't do it properly...they left out some very important risk factors for prostate cancer ... from a scientific standpoint that's what makes this association [between omega-3 DHA blood levels and higher risk for prostate cancer] extremely weak and possibly false.”
Let's take a look at the evidence to date, and then scrutinize the new study … which is clearly weak and non-credible, but has enjoyed a free ride from credulous reporters.
Omega-3s and prostate cancer: A largely positive picture
Most of the published studies and evidence reviews make omega-3s look pretty good for prostate health.
For example, a 2010 evidence review from Montreal's McGill University linked higher seafood consumption to a 63 percent drop in the risk for late-stage or fatal prostate cancer … although it did not find strong evidence that fishy diets curb the risk of getting prostate cancer (Szymanski KM et al. 2010).
And earlier this year, researchers from the Philippines published an evidence review in which they arrived at a similarly positive conclusion:
“High serum [blood] levels of long chain [omega-3] DPA [are] associated with reduced total prostate cancer risk.” (Chua ME et al. 2013)
Interestingly, the Filipino team's only negative conclusion – that higher omega-3 blood levels might increase the risk of high-grade prostate cancer slightly – rested on a flawed 2011 study from the same team behind the new, equally flawed study ... see “Omega-3s Linked, Weakly, to Rare Prostate Cancer
As many expert commentators noted then, the link that its authors made between omega-3s and aggressive prostate cancer were very weak, contradicted by a large body of positive evidence, and lacked scientific credibility.
Let's take a closer look at that same team's new study … and then review the reasons why its conclusions are every bit as unreliable and implausible.
New study links omega-3s to prostate risk, implausibly
The authors of the new study – led by Theodore Brasky, Ph.D., of Ohio State University – analyzed data from a controlled clinical study called the Selenium and Vitamin E Cancer Prevention Trial or SELECT (Brasky TM et al. 2013).
Dr. Brasky's team compared the omega-3 blood levels of 834 men in the SELECT trial who developed prostate cancer over the seven to 12 year span of the trial, with the omega-3 levels in 1,393 men who didn't develop prostate cancer.
They divided the men into four groups, based on their blood levels of various omega-3 and omega-6 fatty acids.
The omega-3s examined included the plant-source, short-chain omega-3 called ALA and the three long-chain omega-3s found only in seafood: EPA, DPA, and DHA.
Omega-3 EPA and DHA are essential to life and health and occur in every cell in the human body … especially our brain, nerve, and eye cells. Omega-3 DPA occurs at very low levels in seafood and in human cells, but increasing evidence suggests that it exerts beneficial health effects.
The Brasky team's analysis showed that the men with the highest blood levels of seafood-source omega-3s were 71 percent more likely to have high-grade prostate cancer, compared with men possessing the lowest levels.
They calculated that the risk of low-grade prostate cancer was 44 percent higher among the men with the highest omega-3 levels, while these men's risk for any grade of prostate cancer was 43 percent higher.
Each 50 percent increase in total long-chain omega-3s (EPA+DHA+DPA) was associated with a 22-25 percent increase in the risk of developing prostate cancer … but the differences in blood levels were too small to constitute credible "dose-response" evidence that omega-3s promote prostate cancer.
Nor did they detect any link between higher prostate risk and higher blood levels of either omega-3 EPA from fish, or omega-3 ALA from plant foods.
Seven reasons for deep skepticism
We do not take the Brasky team's findings lightly, but we see several reasons for skepticism.
Some of these points were made to us by biochemist Douglas Bibus, Ph.D., a leading international expert in fatty acids and blood analysis:
- The authors admit they don't know why omega-3s – which display anti-cancer effects across the board – would promote prostate tumors. This is especially true given that, in the authors' words, the men in the study had “very low concentrations of [omega-3s]”.
- Japanese men had much lower rates of prostate cancer from 1960-2000, compared with men from the U.S., UK, France, or Italy, despite eating much more fish ... hence, much more omega-3 DHA as well (Marugame T, Mizuno S 2005).
- The authors' conclusion that omega-3s raise prostate risks is based on a truly insignificant 0.2% difference in the proportion of omega-3 fatty acids in red blood cells between the men who developed prostate cancer (4.66%) and those who did not (4.48%). And the range in those groups nearly overlapped: the range in men who developed prostate cancer ended at 4.55% while the range in men who did not get prostate cancer started at 4.56%, and the range in men who got high-grade cancer started at 4.51%. This may pass a statistical test, but it doesn't pass the "smell test".
- Men who drank heavily, ate more (proven-unhealthful) trans fats, and smoked had lower rates of aggressive, high-grade prostate cancer ... yet the authors did not conclude that men should smoke, drink more alcohol, and eat more trans fats.
- The blood measure they used – plasma phospholipid fatty acids – is an unreliable gauge of omega-3 levels, developed more than 50 years ago. According to Dr. Bibus, a single fish meal or fish oil supplement will raise the proportion of omega-3s in a person's total phospholipid fatty acids dramatically ... and the men's blood was drawn only once, at the outset of the seven to 12-year study.
- It's entirely possible that the men who developed prostate cancer were generally less healthy, and were taking fish oil supplements.
- Although the authors tried to eliminate “confounding” diet and lifestyle factors that would muddy the waters, it is notoriously hard to do that. And it appears that they authors did not account for the confounding effects of selenium and vitamin E, which were the targets of the original SELECT study. These supplements are implicated in prostate cancer. (Alpha-tocopherol is just one of eight parts of vitamin E, but is the most common supplemental form of "vitamin E". It depletes the body of other vitamin E components, which may be why it is linked to higher prostate risks.)
- As the authors admitted, “Expressing fatty acids as weight proportions could create spurious results because an increase in the percentage of one type of fatty acid requires a decrease in others”. And their justification for dismissing this factor doesn't pass muster: “… however, given the very low concentrations of [omega-3s], it is unlikely that their variability, which is strongly related to dietary intake, would be strongly affected by proportions of other phospholipid fatty acids.” But decades of research on fatty acids analysis suggests that this assertion is a stretch, at best.
Together, these flaws seem serious enough to warrant taking the author's conclusions with a big dose of salt, pending more convincing data.
As they note, we lack a plausible explanation why omega-3 fish fats would appear so beneficial for preventing and/or curbing every major cancer except this one.
Frankly, we're surprised that these researchers gave the results so much more weight than their data and the overall body of evidence on the topic warrants ... a move that will mislead millions of men.
Sadly, we're no longer surprised by the laziness of major media outlets, whose editors failed to scrutinize and challenge a study that rests on weak evidence, is contradicted by prior research, and defies common sense.
- Akinsete JA, Ion G, Witte TR, Hardman WE. Consumption of high ω-3 fatty acid diet suppressed prostate tumorigenesis in C3(1) Tag mice. Carcinogenesis. 2012 Jan;33(1):140-8. doi: 10.1093/carcin/bgr238. Epub 2011 Oct 31.
- Aronson WJ, Kobayashi N, Barnard RJ, Henning S, Huang M, Jardack PM, Liu B, Gray A, Wan J, Konijeti R, Freedland SJ, Castor B, Heber D, Elashoff D, Said J, Cohen P, Galet C. Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy. Cancer Prev Res (Phila). 2011 Dec;4(12):2062-71. doi: 10.1158/1940-6207.CAPR-11-0298. Epub 2011 Oct 25.
- Brasky TM et al. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J Natl Cancer Inst (2013). First published online: July 10, 2013. doi: 10.1093/jnci/djt174. Accessed at http://jnci.oxfordjournals.org/content/early/2013/07/09/jnci.djt174
- Carayol M, Grosclaude P, Delpierre C. Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis. Cancer Causes Control. 2010 Mar;21(3):347-55. doi: 10.1007/s10552-009-9465-1. Review.
- Christensen JH, Fabrin K, Borup K, Barber N, Poulsen J. Prostate tissue and leukocyte levels of n-3 polyunsaturated fatty acids in men with benign prostate hyperplasia or prostate cancer. BJU Int. 2006 Feb;97(2):270-3.
- Chua ME, Sio MC, Sorongon MC, Morales ML Jr. The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: A meta-analysis. Can Urol Assoc J. 2013 May;7(5-6):E333-43. doi: 10.5489/cuaj.1056.
- Chua ME, Sio MC, Sorongon MC, Dy JS. Relationship of dietary intake of omega-3 and omega-6 Fatty acids with risk of prostate cancer development: a meta-analysis of prospective studies and review of literature. Prostate Cancer. 2012;2012:826254. doi: 10.1155/2012/826254. Epub 2012 Oct 18.
- Gerber M. Omega-3 fatty acids and cancers: a systematic update review of epidemiological studies. Br J Nutr. 2012 Jun;107 Suppl 2:S228-39. doi: 10.1017/S0007114512001614. Review.
- Hamazaki K, Higashihara E, Terachi T, Takada H, Matsuda T, Kawakita M, Fuse H, Hamazaki T, Kameyama S, Masai M, Chiba Y, Tokunaga M, Furuya Y, Okegawa T, Murota T, Kawa G, Itomura M. The effect of eicosapentaenoic acid on prostate-specific antigen. In Vivo. 2006 May-Jun;20(3):397-401.
- Heinze VM, Actis AB. Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review. Int J Food Sci Nutr. 2012 Feb;63(1):66-78. doi: 10.3109/09637486.2011.598849. Epub 2011 Jul 15. Review.
- Higashihara E, Itomura M, Terachi T, Matsuda T, Kawakita M, Kameyama S, Fuse H, Chiba Y, Hamazaki T, Okegawa T, Tokunaga M, Murota T, Kawa G, Furuya Y, Akashi T, Hamazaki K, Takada H. Effects of eicosapentaenoic acid on biochemical failure after radical prostatectomy for prostate cancer. In Vivo. 2010 Jul-Aug;24(4):561-5.
- Marugame T, Mizuno S. Comparison of prostate cancer mortality in five countries: France, Italy, Japan, UK and USA from the WHO mortality database (1960-2000). Jpn J Clin Oncol. 2005 Nov;35(11):690-1. Accessed at http://jjco.oxfordjournals.org/content/35/11/690/F2.expansion.html
- Reese AC, Fradet V, Witte JS. Omega-3 fatty acids, genetic variants in COX-2 and prostate cancer. J Nutrigenet Nutrigenomics. 2009;2(3):149-58. doi: 10.1159/000235565. Epub 2009 Sep 23. Review.
- Safarinejad MR, Shafiei N, Safarinejad S. Effects of EPA, γ-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomised, double-blind trial. Br J Nutr. 2012 Nov 30:1-8. [Epub ahead of print]
- Shaikh IA, Brown I, Wahle KW, Heys SD. Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids. Nutr Cancer. 2010;62(3):284-96. doi: 10.1080/01635580903407189. Review.
- Szymanski KM, Wheeler DC, Mucci LA. Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010 Nov;92(5):1223-33. doi: 10.3945/ajcn.2010.29530. Epub 2010 Sep 15. Review.