Recent study implicates omega-3 fatty acids in prostate cancer - Is this reliable information?

Two years ago, I reported on the inconsistent studies on omega-3 fatty acids and prostate cancer risk. Now, a new study has added to the confusion; the media has picked it up and scared men away from omega-3 supplements, meanwhile some experts have criticized the authors’ methodology and conclusions.

This study used data from a clinical trial on vitamin E and selenium supplementation for cancer prevention, and added on a blood test for omega-3 to determine whether there was an association between plasma levels of omega-3 fatty acids and incidence of prostate cancer.  The authors found a statistically significant difference in the average total long-chain omega-3 blood level between men who did or did not develop prostate cancer throughout the study.1

I have serious concerns about the potential risks of taking lots of fish oil capsules.  So much fish oil can have paradoxical effects, reducing immune function in later life.  Plus eating lots of fish exposes you to risky amounts of chemical pollutants, and raises IGF-1, a hormone that is causative in prostate cancer, so it is not that this relationship has no potential to be true.  However, this study does not tell us if these are valid concerns or not and we can’t make any meaningful conclusions from this new study.  This study does NOT indicate that omega-3 supplementation or eating fish are a contributory factor in the prostate cancer equation for numerous reasons.

1.       Plasma vs. erythrocyte fatty acid measurement, done only once

Although measuring omega-3 levels in the blood seems like it would be an objective and accurate indicator of fish oil intake compared to using the subjects’ reported dietary intake, this test does not  accurately reflect long-term dietary intake. There are two methods for measuring blood fatty acids; in plasma or in erythrocyte (red blood cell) membranes.  Erythrocyte omega-3 measurement has been reported to be a more accurate reflection of long-term blood levels, and to correlate more closely with dietary intake compared to plasma measurement.2   Regardless of which test was used, one blood test does not reflect one’s fish oil intake or fish exposure over a lifetime or even over a twenty year period.  Cancer is caused by what you do for many, many years, not what you do for a few weeks or months.   You would have to do multiple blood tests over many years to assure the results were indicative of a dietary pattern.  Also, since there was only one blood test at baseline in this study (and they used plasma levels), it only reflects what they consumed a few days before the test was drawn. This is very important, since cancer takes many years to develop. Some men that did have higher levels may have started taking fish oils supplements only recently, and some may have simply eaten a large piece of fish the night before the blood test.

2.       The tiny difference in blood omega-3s between the cases and controls.

The authors found a statistically significant difference in the average total omega-3 blood level between men who did or did not develop prostate cancer throughout the study. But is this a meaningful difference out in the real world?  In men diagnosed with prostate cancer, the average was 4.66% of total fatty acids; in men without cancer, the average was 4.48%. This is a very small difference, and likely reflects an insignificant difference in omega-3 intake.   

3.       No information on fish, fish oil, or other omega-3 supplement intake of subjects.

Where did the slight difference in omega-3 blood levels come from? Were the men who were diagnosed with cancer more likely to be taking fish oil capsules? Were they eating more fish overall?  More breaded and fried fish? More large, predator fish? The type of fish and how it is prepared would impact the level of environmental contaminants and dietary carcinogens.  Could the early development of prostate cancer increase blood omega-3s, rather than vice versa? 3 These unanswered questions make it very difficult to extract any useful information from this study’s results.  For it to have substantive impact they would have had to track dietary fish consumption, fish oil consumption and have confirm that was a true recall, with confirmatory blood tests taken episodically. 

4.       Rancid fish oil?

Industry experts have pointed to the potential role of rancid fish oil in the inconsistent results among omega-3 studies. Animal studies have shown that rancid fish oil could promote inflammation and even cancer, and the majority of fish oil capsules are indeed rancid. Omega-3s are highly unstable fats, very susceptible to oxidation, forming lipid peroxides and starting a chain of oxidation reactions leading to rancidity.  Exposure of EPA and DHA to light, heat and oxygen increase the likelihood of oxidation.4

(Fresh, non-rancid fish oil does not have an unpleasant taste or smell. If you take omega-3 capsules, open one up and taste the oil to test whether it has gone rancid.)  

5.       Research on omega-3s and prostate cancer remains inconsistent.

The authors state, “It is unclear why high levels of long-chain omega-3 PUFA would increase prostate cancer risk, and further study will be needed…” As discussed in my previous article, the literature on omega-3 fatty acids and prostate cancer is indeed inconsistent.

A 2010 meta-analysis of 31 studies on fish consumption and prostate cancer risk found no significant effect overall, and noted the inconsistency between studies: the risks of prostate cancer diagnosis calculated for high fish consumption ranged from a 61% decrease to a 77% increase.5  A 2013 meta-analysis of studies on blood omega-3 levels and prostate cancer also found no effect overall on prostate cancer risk, and noted significant heterogeneity (inconsistency in results) between studies. Only after removing one study from their analysis did they see an increased risk of high-grade prostate cancer.6  Interestingly, Asian populations, such as in Japan, that consume high levels of fish tend to have lower rates of prostate cancer.7-9 The 2010 meta-analysis also found a 63% decrease in risk of death from prostate cancer with high fish consumption.5  Many studies have shown that DHA and EPA decrease proliferation and increase cell death in prostate cancer cells, and that omega-3-enriched diets slow prostate tumor growth in animals.10-20  A clinical trial published in 2011 gave patients about to undergo prostatectomy either a low-fat (15% of calories) diet plus fish oil supplementation or a Western diet with no supplements for 4-5 weeks prior to surgery. The fish oil supplemented group showed a 32.2% decrease in malignant cell proliferation when prostate tissue was analyzed after surgery.21  Though many people with biases want to jump on the results of one of these studies to claim fish or fish oil are good or bad, we simply cannot do so with scientific integrity.   There are many different studies on this topic with widely varying results.

Omega-3 supplementation: the big picture

For optimal health (including cancer protection), we require the complete composition of the nutrient-dense (Nutritarian) diet that supplies us with optimal amounts of all valuable nutrients and phytochemicals.  Avoiding deficiencies is critical, but it is important to avoid excesses too.  Omega-3 fatty acids are essential nutrients that we must get from our diets because our bodies cannot make them; they are crucial for early brain development, and there is much evidence that they promote cardiovascular health and cognitive function.22,23  Note also, that higher omega-3 blood levels have been associated with reduced risk of death from all causes.24  Avoiding supplemental omega-3s is not the appropriate response to this new study.  This is especially critical because we all convert short chain omega-3 (ALA) into long chain omega-3 (DHA) differently, and if you are one of those poor converters, the lack of DHA in your diet can turn out to be devastating to you in later life.  Many vegans are gambling with their future cognitive health to uphold a philosophical viewpoint, because once you develop a neurological or cognitive deficit in later life, it will be too late to try to fix a deficiency that could have caused it. 

Of course, too much of any potentially good thing turns it bad.  For any needed nutrient, especially fat soluble nutrients, too much can be problematic.  Since all fish oil capsules give a pretty high dose of EPA and DHA, and most of them are rancid too, they could be part of the problem. Plus, fish is an unfavorable omega-3 source, since animal protein and environmental contaminants are packaged with the DHA and EPA.   I advise most people take a low dose of algae-derived EPA-DHA, or follow your omega-3 levels episodically to assure no deficiency exists.  Maintaining adequate, but not excessively high DHA and EPA levels is the safest and most conservative and responsible strategy. 

 

References:

1. Brasky TM, Darke AK, Song X, et al: Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J Natl Cancer Inst 2013.
2. Sun Q, Ma J, Campos H, et al: Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women. Am J Clin Nutr 2007;86:74-81.
3. Liu Y: Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer. Prostate Cancer Prostatic Dis 2006;9:230-234.
4. Albert BB, Cameron-Smith D, Hofman PL, et al: Oxidation of marine omega-3 supplements and human health. Biomed Res Int 2013;2013:464921.
5. Szymanski KM, Wheeler DC, Mucci LA: Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr 2010;92:1223-1233.
6. Sorongon-Legaspi MK, Chua M, Sio MC, et al: Blood level omega-3 Fatty acids as risk determinant molecular biomarker for prostate cancer. Prostate Cancer 2013;2013:875615.
7. Dewailly E, Mulvad G, Sloth Pedersen H, et al: Inuit are protected against prostate cancer. Cancer Epidemiol Biomarkers Prev 2003;12:926-927.
8. Kobayashi M, Sasaki S, Hamada GS, et al: Serum n-3 fatty acids, fish consumption and cancer mortality in six Japanese populations in Japan and Brazil. Jpn J Cancer Res 1999;90:914-921.
9. Hebert JR, Hurley TG, Olendzki BC, et al: Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study. J Natl Cancer Inst 1998;90:1637-1647.
10. Cavazos DA, Price RS, Apte SS, et al: Docosahexaenoic acid selectively induces human prostate cancer cell sensitivity to oxidative stress through modulation of NF-kappaB. Prostate 2011.
11. Hu Y, Sun H, Owens RT, et al: Syndecan-1-dependent suppression of PDK1/Akt/bad signaling by docosahexaenoic acid induces apoptosis in prostate cancer. Neoplasia 2010;12:826-836.
12. Chung BH, Mitchell SH, Zhang JS, et al: Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells. Carcinogenesis 2001;22:1201-1206.
13. Rose DP, Connolly JM: Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines. Prostate 1991;18:243-254.
14. Bureyko T, Hurdle H, Metcalfe JB, et al: Reduced growth and integrin expression of prostate cells cultured with lycopene, vitamin E and fish oil in vitro. Br J Nutr 2009;101:990-997.
15. Istfan NW, Person KS, Holick MF, et al: 1alpha,25-Dihydroxyvitamin D and fish oil synergistically inhibit G1/S-phase transition in prostate cancer cells. J Steroid Biochem Mol Biol 2007;103:726-730.
16. Yi L, Zhang QY, Mi MT: [Role of Rho GTPase in inhibiting metastatic ability of human prostate cancer cell line PC-3 by omega-3 polyunsaturated fatty acid]. Ai Zheng 2007;26:1281-1286.
17. Nakajima T, Kubota N, Tsutsumi T, et al: Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells. Br J Pharmacol 2009;156:420-431.
18. Aronson WJ, Barnard RJ, Freedland SJ, et al: 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;183:345-350.
19. Berquin IM, Min Y, Wu R, et al: Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. J Clin Invest 2007;117:1866-1875.
20. Kelavkar UP, Hutzley J, Dhir R, et al: 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;8:112-124.
21. Aronson WJ, Kobayashi N, Barnard RJ, et al: Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy. Cancer Prev Res (Phila) 2011;4:2062-2071.
22. Simopoulos AP: The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood) 2008;233:674-688.
23. Simopoulos AP: Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol Neurobiol 2011;44:203-215.
24. Mozaffarian D, Lemaitre RN, King IB, et al: Plasma Phospholipid Long-Chain omega-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study. Ann Intern Med 2013;158:515-525.


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Comments (3) Read through and enter the discussion with the form at the end
NevadaSmith - July 19, 2013 6:40 PM

What I would like to know is: What about Arctic Ruby oil aka Calanus oil?

Stephen Albers - July 19, 2013 7:09 PM

I use the Quant test to verify my EPA/DHA status. What level on the Quant finger prick test do you consider optimum for Nutritarians?

Deana Ferreri, PhD - July 24, 2013 10:41 AM

Nevada,
Calanus oil, similar to other fish oils, is rich in DHA and EPA. Because it is lower on the food chain, it is thought to be lower in pollutants than other fish oils. However, lab-grown algae would still be a cleaner source of DHA and EPA.

Stephen,
According to Dr. Fuhrman, greater than 4 in the OmegaQuant test is likely sufficient, and greater than 5 is certainly sufficient.

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