July 17, 2013

Fish Oil and Prostate Cancer? Be Suspect

Posted in: Health and Nutrition, Latest News

by Ellen Troyer, MT MA
Biosyntrx CEO / Chief Research Officer
Voting Member, Council for Responsible Nutrition

A number of alarmist are suggesting that Omega-3 fatty acid intake increases prostate cancer risks, based on questionable follow-up conclusions of a 2011 prospective study published in The Journal of the National Cancer Institute.

Here is a quick analysis of these conclusions by the science team at the Washington, D.C. Council for Responsible Nutrition:

Study Design
Case cohort study evaluating plasma fatty acid levels and prostate cancer risk in patients from the Selenium and Vitamin E Cancer Prevention Trial (SELECT):

Results
The findings indicate that men with the highest 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 increased risk of prostate cancer.

The study reports a 71 percent increased risk of advanced state prostate cancer; a 44 percent increase in the risk of early prostate cancer and an overall 43 percent increase in risk for total prostate cancer.

Also noteworthy and counterintuitive is that omega-6 fatty acids (considered pro-inflammatory) and trans-fatty acids were not associated with risk of prostate cancer.

Scientific Analysis
There is no evidence that anyone in the SELECT study took fish oil dietary supplements. There is also no documentation of fish oil or fish intake in the study group. Does the concluding statement by the authors show the true intent of their research? “There is really no evidence that taking dietary supplements is beneficial to health, and there is increasing evidence that taking high doses is harmful.”

It is a known fact that sick people take omega-3 at a higher rate than healthy people, and plasma levels of omega-3 only provide insight into the recent habits of these people.

• This study could have simply been measuring a marker reflecting recent intake of fish or fish oil in a group of high risk cancer patients that have been told to increase their EPA and DHA levels, as compared to a group of non-cancer patients that have not been told to consume more EPA and DHA.

• Plasma levels of EPA and DHA reflect very recent intake and are considered a poor marker of long term omega-3 intake, especially when compared to red blood cell levels, which reflect medium term intake. It has been shown that a single fish oil dose massively increases plasma omega-3 in about 4-12 hours that washes out in about 48 hours.

Other research has recently shown that subjects often take fish oil prior to study visits.

By concluding that men are at a higher risk of aggressive prostate cancer based on a 0.2 percent difference in omega-3 levels, the authors are claiming a “significant” response with an “insignificant” difference in an emerging marker that has not been evaluated.

• The authors are concluding that men are at higher risk of aggressive prostate cancer if the plasma level of omega-3 is 4.7% versus 4.5%.

• This means that one fast food fish sandwich that contains 35 mg of omega-3 will push blood levels into the danger zone. If the findings are true, then aggressive prostate cancer would be rampant in any country with any seafood consumption, and dates back to early mankind.

• This is analogous to saying a 1 point difference in LDL-cholesterol increases death from heart attack by 71%

A secondary analysis with outlier results has to be assessed in context with the total body of evidence.

• This is a secondary analysis of data and markers taken from subjects enrolled in the SELECT trial, which is a study that was not originally designed to assess omega-3 levels and prostate cancer risk. Therefore, scientific standards dictate that results from this study should not be considered conclusive.

• In addition, results from this study are not consistent with previous evidence (see below) and the fact is the 71 percent increase in aggressive prostate cancer associated with omega-3 fatty acid consumption is an extreme outlier that should raise suspicions regarding the results of this study.

Furthermore, this study has several counterintuitive findings that should also raise suspicions. For example, people who smoked and consumed more alcohol at baseline had higher incidence of aggressive prostate cancer. If these results are taken at face value, doctors would recommend that men should smoke, drink, and reduce fish intake.

Other Studies with Conflicting Results
Researchers investigated the effect of dietary fish intake amongst 6,272 Swedish men who were followed-up for 30 years. That study reported that men who ate no fish had a two- to three-fold increase in the risk of developing prostate cancer compared with those who consumed large amounts of fish in their diet. (Terry et al. 2001)

Another prospective cohort study based on the Physician’s Health Study found that fish consumption more than 5 times per week) was not related to prostate cancer risk but was preventive of prostate cancer–specific death. (Chavarro et al. 2008)

Other studies have suggested lower prostate cancer risk with omega-3 fatty acids from fish in Swedish men (Norrish AE, et al.) and in Japanese and Brazilian men (Kobayashi et al. 1999).

A large prospective cohort, established in 1986, looked at 51,529 American men, 40 – 75 years of age, who completed a mailed questionnaire about demographic and medical information; found that a high intake of fish was associated with a lower risk of metastatic prostate cancer.

An important clinical study published by a group at the Harvard School of Public Health examined the link between dietary fish consumption and the risk of metastatic prostate cancer. This paper reported results from the Health Professionals Follow-up Study that involved 47,882 men over twelve years. During the twelve years, 2,483 cases of prostate cancer were identified. Of these, 617 were advanced and of these, 278 were metastatic. Eating fish more than three times a week reduced the risk of prostate cancer but had an even greater impact on the risk of metastatic prostate cancer. For each additional 500 mg of marine fat consumed the risk of metastatic disease decreased by 24%! (Augustsson, et al. 2003).

In a meta-analysis (a study of studies), Szymanski and his team found a significant 63 percent reduction in prostate cancer-specific mortality in those that consumed fish but no link between eating lots of fish and men’s risk of developing prostate cancer. (Szymanski et al. 2010).

PEARL
One wonders who is responsible for the current rash of questionable studies and articles suggesting dietary supplements may be dangerous.

This is particularly disturbing given the lack of nutrition associated with the Standard American Diet (SAD); given the vast amount of science suggesting that even slight nutritional deficiencies, over time, greatly contribute to degenerative disease, and given the safety records of dietary supplements vs. pharmaceutical drugs.


References

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: 1866–75 [abstract]

Chua ME, Sio MC. et al. The relevance of serum levels of long chain opema-3 polyunsaturated fatty acids and prostate cancer risk: A meta-analysis. Can Urol Assoc J. 2013 May;7(5-6); [abstract]

Torfadottri JE, Valdimarsdottir UA> Consumption of fish products across the lifespan and prostate cancer risk. PLoS One 2013 Apr 17;8(4) [abstract]

Sorongon-Legaspi MK, Chus M, et al. Blood level omega-3 fatty acids as a risk determinant molecular biomarker for prostate cancer. Prostate Cancer 2013; [abstract]

Wang MT, Honn KV, Nie D. Cyclooxygenases, prostanoids, and tumor progression. Cancer Metastasis Rev 2007; 26: 525–34 [abstract]

Brasky TM, Darke AK, et al. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J J Nat Cancer Inst 2013 Jul 10, 2013. [abstract]

Dahm CC, Gorst-Rasmussen A, et al. Fatty acid patterns and risk of prostate cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2012 Dec; 96(6): 1354-61. [abstract]

Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Fatty fish consumption and risk of prostate cancer. Lancet 2001; 357: 1764–6 [abstract]

Chavarro JE et al. A 22-y prospective study of fish intake in relation to prostate cancer incidence and mortality. Am J Clin Nutr 2008; 88: 1297–303. [abstract]

Augustsson, K., et al., A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiol Biomarkers Prev, 12(1): p. 64-7, 2003.[abstract]

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. [abstract]

Leitzmann MF, Stampfer MJ, Michaud DS, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr. 2004 Jul;80(1):204-16. [abstract]

Ritchie JM, Vial SL, Fuortes LJ, Robertson LW, Guo H, Reedy VE, Smith EM.Comparison of proposed frameworks for grouping polychlorinated biphenyl congener data applied to a case-control pilot study of prostate cancer. Environ Res. 2005 May;98(1):104-13. [abstract]

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