Omega-3 Diet Reduced Prostate Risk Factors
New human study rebuts deeply flawed but headline-making report
New human study rebuts deeply flawed but headline-making report
Please see my Author's Note sidebar, below.
Prostate cancer is a leading cause of death among men in the United States.
Some 230,000 American men will be diagnosed this year, and more than 29,000 will die from it.
Sadly, the remarkably misleading conclusions of a prostate cancer study published last summer caused men pointless confusion and concern … and scared them away from healthful fish and fish oil.
Most major news outlets simply repeated its authors' alarmist and unsupported, distorted conclusions … lazily and uncritically.
Monday, January 13, 2014
This article left an unclear impression of the evidence on omega-3s and prosate cancer.
I should have noted that several prior epidemiological studies found that men with high-grade prostate cancer also had higher blood levels of omega-3 DHA or EPA from fish or fish oil or of omega-3 ALA from green plants and some seeds (Crowe FL 2008; Brasky TM et al. 2011; Brasky TM et al 2013).
However, many epidemiological studies have not linked higher omega-3 levels to increased risk, or linked them to reduced risk (Gann PH et al. 1994; Godley PA et al. 1996; Harvei S et al. 1997; Newcomer LM et al. 2001; Männistö S et al. 2003; Laaksonen DE et al. 2004; Chavarro JE et al. 2007; Ukoli FA et al. 2009).
And, as many experts said in critiquing the flawed conclusions of a 2012 evidence review ... which focused on epidemiological studies involving men diagnosed with prostate cancer ... those men may have been eating more fish or taking more fish oil in hope of curbing the course of their disease.
And the seemingly negative studies were epidemiological investigations, not controlled clinical trials.
As described in this article, a new clinical trial from UCLA adds good evidence suggesting a protective role for a low-fat diet rich in omega-3s.
As a controlled (albeit small and short-term) clinical trial, it has considerable scientific credibilty ... although it concerns the progression. not the prevention of prostate cancer.
And it is supported by human and lab research into how omega-3s affect known risk factors for prostate cancer.
Still, we need large, controlled clinical trials to gain a clear, definitive picture.
In that study, researchers from Ohio State University analyzed omega-3 levels in blood samples from participants in a clinical trial testing vitamin supplements against prostate cancer.
They found a very slight statistical link between higher omega-3 DHA blood levels and the risk of aggressive prostate cancer … and issued clearly unjustified, context-free conclusions and recommendations.
Experts in prostate cancer and omega-3s quickly pointed out the fatal flaws in the authors' conclusions, as we reported in “Fishy Prostate News”.
For example, Harvard prostate cancer specialist Anthony D'Amico, M.D., called the Ohio State team's findings “extremely weak and possibly false.”
Importantly, that flawed analysis contradicted, very unconvincingly, the overwhelming majority of prior research.
Overall, the evidence from cells, animals, and human studies supports the likely, plausible prospect that omega-3-rich diets help protect men's prostates from cancer and/or slow its spread (e.g., “Positive Omega-3/Prostate Trial”).
Since most men who die from prostate cancer do so very late in life, slowing its growth could be tantamount to preventing death or disability from the disease.
Before reviewing the latest good news about omega-3s and prostate cancer, let's look at the California-based 2011 trial behind the encouraging new findings.
UCLA study found omega-3s protective
Three years ago, California-based scientists reported positive results from a clinical trial testing the effects of omega-3 supplements in men undergoing radical prostatectomy (Aronson WJ et al. 2011).
As they wrote, ample evidence suggests that omega-3s discourage prostate cancer, while the average American's excessive intake of omega-6 fats (from cheap vegetable oils) raises the risk and lethality of prostate cancer: “Pre-clinical studies suggest [that] lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression.”
They conducted a randomized clinical trial to test the effect of reducing dietary fat intake and men's' omega-6:omega-3 intake ratio.
Men undergoing radical prostatectomy were randomly assigned to one of two diets for four to six weeks prior to surgery:
- Standard American Diet: high-fat (40 percent of calories) diet with an omega-6:3 ratio of 15:1
- Omega-3 Diet: low-fat (15 percent of calories) diet plus 5 grams of fish oil, with an omega-6:3 ratio of 2:1
The Standard American diet's fat sources were typical of the American diet, featuring high levels of omega-6 fats from corn oil, and low levels of omega-3s from fish.
Encouragingly, prostate cancer spread less among the men who ate the low fat Omega-3 Diet.
And the men on the Omega-3 Diet showed beneficial changes in the cell membranes of both the healthy cells and the cancer cells:
- Higher levels of (anti-inflammatory) omega-3 fatty acids (from their diet's fish oil)
- Lower levels of the (pro-inflammatory) omega-6 fatty acids (from their diet's corn oil)
Chronic, unhealthful inflammation fuels cancers, and the body uses omega-3 fatty acids to moderate and end inflammation.
With some exceptions, the omega-6 fats abundant in seeds, nuts, and most vegetable oils generally sustain inflammation.
And this outcome prompted the authors to call for more study: “These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology.” (Aronson WJ et al. 2011)
Now, further analysis of data from this California-based 2011 study offers more evidence that seafood-source omega-3s are allies against prostate cancer … not risk factors for it.
New California trial supports omega-3s' protective potential
Deeper analysis of data from the 2011 California-based clinical trial further undermines the credibility of the deeply flawed, alarmist Ohio State study published last summer (Galet C et al. 2013).
The prostate cancer patients assigned to the Omega-3 Diet (low-fat diet 5 grams of fish oil) daily showed key benefits, versus the control group eating a standard American diet:
- Lower levels of pro-inflammatory substances in their blood
- Lower scores on a measure used to predict cancer recurrence, called CCP
According to lead author William Aronson, M.D., lowering the cell cycle progression (CCP) score may help prevent prostate cancers from becoming more aggressive:
“CCP scores were significantly lower in the prostate cancer in men who consumed the low-fat fish oil diet ... This is of great interest, as the CCP score in prostate cancer is known to be associated with more aggressive disease ...” (UCLAHS 2013)
His team also found that men on the low-fat Omega-3 Diet had lower blood levels of pro-inflammatory substances associated with cancer.
As Aronson said, when they found lower blood levels of a pro-inflammatory agent called LTB4 in the Omega-3 group, as well as lower CCP scores, “... we discovered a completely novel finding that one of the receptors for LTB4 is found on the surface of prostate cancer cells.” (UCLAHS 2013)
In other words, the low-fat Omega-3 Diet lowered levels of a previously unknown promoter of prostate cancer ... one that the California team unmasked for the first time.
“These studies are showing that, in men with prostate cancer, you really are what you eat,” Aronson said. “The studies suggest that by altering the diet, we may favorably affect the biology of prostate cancer.” (UCLAHS 2013)
The study was funded by the National Institutes of Health (NIH).
Based on their results, Aronson will start a prospective, randomized trial in 100 men, next year.
The volunteers will eat their usual diet or to a low-fat, omega-3-enriched diet, and will receive a prostate biopsy at the beginning of the trial and again one year later.
Aronson's team will then measure markers in the prostate biopsy tissue to check for cell growth and CCP (cancer growth) scores.
We'll let you know how that turns out.
In the meantime, the evidence clearly supports the idea that fish-source omega-3s help protect prostate health.
Aronson WJ, Barnard RJ, Freedland SJ, Henning S, Elashoff D, Jardack PM, Cohen P, Heber D, Kobayashi N. Growth inhibitory effect of low fat diet on prostate cancer cells: results of a prospective, randomized dietary intervention trial in men with prostate cancer. J Urol. 2010 Jan;183(1):345-50. doi: 10.1016/j.juro.2009.08.104. Epub.
Aronson WJ, Glaspy JA, Reddy ST, Reese D, Heber D, Bagga D. Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer. Urology. 2001 Aug;58(2):283-8.
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.
Azrad M, Demark-Wahnefried W. Dietary omega-6 and omega-3 fatty acids and prostate cancer - letter. Cancer Prev Res (Phila). 2012 May;5(5):798; author reply 799. doi: 10.1158/1940-6207.CAPR-12-0032. Epub 2012 Apr 3.
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 Aug 7;105(15):1132-41. doi: 10.1093/jnci/djt174. Epub 2013 Jul 10.
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 Jun 15;173(12):1429-39. doi: 10.1093/aje/kwr027. Epub 2011 Apr 24.
Chavarro JE, Stampfer MJ, Li H, Campos H, Kurth T, Ma J. A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1364-70. Epub 2007 Jun 21.
Crowe FL, Allen NE, Appleby PN, Overvad K, Aardestrup IV, Johnsen NF, Tjønneland A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Zavitsanou A, Trichopoulos D, Sacerdote C, Palli D, Tumino R, Agnoli C, Kiemeney LA, Bueno-de-Mesquita HB, Chirlaque MD, Ardanaz E, Larrañaga N, Quirós JR, Sánchez MJ, González CA, Stattin P, Hallmans G, Bingham S, Khaw KT, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ. Fatty acid composition of plasma phospholipids and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2008 Nov;88(5):1353-63.
Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MT 4th, Snyder DC, Owzar K, Hars V, Albala DM, Walther PJ, Robertson CN, Moul JW, Dunn BK, Brenner D, Minasian L, Stella P, Vollmer RT. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3577-87. doi: 10.1158/1055-9965.EPI-08-0008.
Galet C, Gollapudi K, Stepanian S, Byrd JB, Henning SM, Grogan T, Elashoff D, Heber D, Said J, Cohen P, Aronson WJ. Effect of a Low-Fat Fish Oil Diet on Proinflammatory Eicosanoids and Cell-Cycle Progression Score in Men Undergoing Radical Prostatectomy. Cancer Prev Res (Phila). 2013 Dec 19. [Epub ahead of print]
Gann PH et al. 1994; Godley PA et al. 1996; Harvei S et al. 1997; Newcomer LM et al. 2001; Männistö S et al. 2003; Laaksonen DE et al. 2004; Chavarro JE et al. 2007; Ukoli FA et al. 2009
Gann PH, Hennekens CH, Sacks FM, Grodstein F, Giovannucci EL, Stampfer MJ. Prospective study of plasma fatty acids and risk of prostate cancer. J Natl Cancer Inst. 1994 Feb 16;86(4):281-6. Erratum in: J Natl Cancer Inst 1994 May 4;86(9):728.
Godley PA, Campbell MK, Gallagher P, Martinson FE, Mohler JL, Sandler RS. Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma. Cancer Epidemiol Biomarkers Prev. 1996 Nov;5(11):889-95.
Harvei S, Bjerve KS, Tretli S, Jellum E, Robsahm TE, Vatten L. Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer. Int J Cancer. 1997 May 16;71(4):545-51.
Kelavkar UP, Hutzley J, Dhir R, Kim P, Allen KG, McHugh K. Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy. Neoplasia. 2006 Feb;8(2):112-24.
Kobayashi N, Barnard RJ, Henning SM, Elashoff D, Reddy ST, Cohen P, Leung P, Hong-Gonzalez J, Freedland SJ, Said J, Gui D, Seeram NP, Popoviciu LM, Bagga D, Heber D, Glaspy JA, Aronson WJ. Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2. Clin Cancer Res. 2006 Aug 1;12(15):4662-70.
Laaksonen DE, Laukkanen JA, Niskanen L, Nyyssönen K, Rissanen TH, Voutilainen S, Pukkala E, Hakkarainen A, Salonen JT. Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: a population-based cohort study. Int J Cancer. 2004 Sep 1;111(3):444-50.
Männistö S, Pietinen P, Virtanen MJ, Salminen I, Albanes D, Giovannucci E, Virtamo J. Fatty acids and risk of prostate cancer in a nested case-control study in male smokers. Cancer Epidemiol Biomarkers Prev. 2003 Dec;12(12):1422-8.
Newcomer LM, King IB, Wicklund KG, Stanford JL. The association of fatty acids with prostate cancer risk. Prostate. 2001 Jun 1;47(4):262-8.
Terry PD, Rohan TE, Wolk A. Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence. Am J Clin Nutr. 2003 Mar;77(3):532-43. Review.
Ukoli FA, Akumabor PN, Oguike TC, Dent LL, Beech D, Osime U. The association of plasma fatty acids with prostate cancer risk in Nigerians. Ethn Dis. 2009 Autumn;19(4):454-61.
University of California - Los Angeles Health Sciences (UCLAHS). Men with prostate cancer who ate a low-fat fish oil diet showed changes in their cancer tissue. November 18, 2013. Accessed at http://www.eurekalert.org/pub_releases/2013-11/uoc--mwp111813.php