You Expect Me To Believe That?

fishoil-hookSome things just belong together. Not too many of us eat only the meringue from the lemon pie. Sauerkraut on a bun without the sausage isn’t quite the same gustatory delight. And sometimes the aunt is more fun when in the company of the uncle. Such is the case with essential fatty acids. The omega-3’s can do their job without the omega-6’s, but the outcome will eventually be out of whack. It’s this imbalance that wrought the nefarious genius of a twisted, fear-huckstering fish oil report, so carefully crafted that the typical reader comes to believe that black is white.

The study reported in the Journal of the National Cancer Institute determined a positive relationship of non-vegetable sourced omega-3 fatty acids to prostate cancer. If non-vegetable, that leaves fish oil, known better for its downstream n-3 fats, EPA and DHA, than for the mother n-3, alpha-linolenic acid. The concern with this proposition is that the authors seem to have gone from home plate to home plate, in a 360-foot path without ever touching any of the bases. Healthy incredulity befits the reading of a ‘scientific’ paper. That leaves questions that most of us don’t ponder, including these:  Why would anyone take n-3 fats without also taking n-6 complements? Did any of the subjects bear a pre-existing pathology? Were the supplements, if used, of sufficiently high quality, as you would expect from a cGMP-obligated company? (The term “pharmaceutical grade” means only that toxins have been removed, and is otherwise unregulated, since many products that call themselves fish oil are not oils but ethyl esters instead of triglycerides.) Is it possible that individuals were removed from the study because they got healthy all of a sudden? Not to be too picky, but what were the capsules themselves made from, if supplements are to blame? Could the supplements have been combined with active pharmaceuticals or with contraindicated other supplements? Not finally, but at least additionally, why is it so that countries whose cuisine is dominated by fish—Scandinavia or Japan—do not also present a high level of prostate cancer? Funny thing:  this study failed to tell us where the men in this investigation got their omega-3 fats. The dollar store? Canned tuna? Maybe from the fish they ate an hour prior to the blood draw?

The Public Library of Science has a journal called PLoS One. It covers primary research in science and medicine, submissions of which are subjected to intense scrutiny and peer review. However, the Journal does invite post-publication discussion and critique. In its April, 2013 issue, it printed an Icelandic study on consumption of fish products and the risk of prostate cancer. There were almost 2300 men, aged 67 and up, in this four-year project. Except for processed fish that was salted or smoked, fish oil or very high fish consumption was determined not to be associated with early or midlife prostate cancer risk (Torfadottir, 2013). Hmm. Go figure. Earlier Canadian meta-analysis discovered a 63% reduction in prostate-cancer-specific mortality among fish eaters, but no incipient protective effect by fish ingestion (Szymanski, 2010). That means eating fish did not prevent disease. There are other causes, such as too much conventionally raised red meat.

There is a strong suggestion in a Harvard study that total fat and certain saturated fatty acids may be implicated in prostate disease incidence, but that, “Among all men, those with the highest omega-3 docosahexaenoic acid and total marine fatty acid intakes were 40% less likely to die from prostate cancer,” adding that “…high marine omega-3 fatty acid intake may improve disease-specific survival for all men” (Epstein, 2012). Although the source of DHA is not identified in the study in question, an Italian work cited the 22:6 n-3 as protective against physiological activities involved in the progression of prostate cancer cells (Bianchini, 2012).  Marshall University mice that were fed a high n-3 diet containing fish oil concentrate presented with a decreased expression of genes expected to increase proliferation of prostate cancer cells by virtue of lowering estradiol values (Akinsete, 2012).

What about the n-6 to n-3 ratio we mentioned earlier?  Glad you asked. In no particular order, try reading these authors  to get the picture that n-3 fats need the accompaniment of the n-6 fats: (vanJaarsveld, 1997) (Ramirez0Silve, 2011) (Caramia, 2008) (Wijendran, 2004) (Simopoulos, 2002, 2008) (Gomez, 2011) (Yehuda, 1993, 1996). The additional info you need to find these is at the end of this piece. The ideal omega-6 to omega-3 ratio is generally agreed to be 4 to 1. That’s four times the omega-6 as omega-3. How come?  The enzymes that desaturate and elongate fatty acids prefer to work along the n-3 pathway, and by the time they get to the n-6 fats, part of the n-6’s have been burned for energy. Also, the enzyme pathway could be interrupted by age, booze, trans-fats, disease and overdose of dietary cholesterol (which is a good thing that can be overdone).

If fish oil is held culpable, which form?  The ethyl ester form (EE) is made when the glycerol backbone of fish body oil is removed during molecular distillation and replaced by an ethanol, allowing the process to be completed at a lower temperature. It isn’t a fat any more, and really shouldn’t be allowed to be called an oil. This is now an ester that is not digested and absorbed by the body in the same manner as the original triglyceride. Once distilled, true fish oil has its triglyceride put back in a process called re-esterification, or re-concentration, a procedure that adds about 40% to the cost of the finished product. But this replacement of the glycerol—fish oil is a triglyceride—returns the substance to its natural state. Fish oil that has an alcohol head is metabolized just like an alcohol from liquor, and that’s not what we expect from a supplement that’s supposed to be a boon to health. Bioavailability of re-esterified triglycerides is superior to all other forms of fish oil (Dyerberg, 2010).

The study in question (Brasky, 2013) is of an observational nature, not experimental, such as a randomized, controlled, double-blinded trial would be.  Observational studies are not used as reliable sources, though they can help to formulate hypotheses to be used in subsequent experiments (Nahin, 2012). Additionally, cause-effect has not been established. The paper was quick to point the finger at a dietary supplement. True, many supplements are misused for lack of direction by a qualified health care practitioner, such as a dietitian or clinical nutritionist. But that can be resolved with a phone call and an appointment. Mega-doses of fish oil do not mix well with drugs or supplements that thin the blood. If a person doesn’t know that, he needs to. Though there is no established upper limit for fish oil, six grams might be too much, while two or three grams might just be on the mark for most adults. Actual dosage depends on the fish species and the levels of EPA and DHA in the product.

To balance the omega-3 fatty acids, evening primrose oil (EPO) is a good source of omega-6 fats, particularly of gamma-linolenic acid (GLA), which is the preferred launching point for conversion to the longer derivatives. Yes, borage oil has more GLA than EPO, but also contains alkaloids that can tax the liver.

An interesting comment from the University of Guelph in Ontario, Canada is, “I have no idea how this paper got accepted for publication.”  (Professor Gopinadhan Paliyath)



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.

Astorg P.
Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence.
Cancer Causes Control. 2004 May;15(4):367-86.

Beckermann B, Beneke M, Seitz I.
Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers.
Arzneimittelforschung. 1990 Jun;40(6):700-4.

Bianchini F, Giannoni E, Serni S, Chiarugi P, Calorini L.
22 : 6n-3 DHA inhibits differentiation of prostate fibroblasts into myofibroblasts and tumorigenesis.
Br J Nutr. 2012 Dec 28;108(12):2129-37

Brasky TM, Crowe FL, Kristal AR.
n-3 Fatty acids and prostate cancer risk.
Br J Nutr. 2012 Nov 14;108(9):1721.

Theodore M. Brasky, Amy K. Darke, Xiaoling Song, Catherine M. Tangen, Phyllis J. Goodman, et al
Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial
JNCI J Natl Cancer Inst (2013) doi: 10.1093/jnci/djt174 First published online: July 10, 2013

Caramia G.
The essential fatty acids omega-6 and omega-3: from their discovery to their use in therapy
Minerva Pediatr. 2008 Apr;60(2):219-33.

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.

Dyerberg J, Madsen P, Møller JM, Aardestrup I, Schmidt EB.
Bioavailability of marine n-3 fatty acid formulations.
Prostaglandins Leukot Essent Fatty Acids. 2010 Sep;83(3):137-41.

Epstein MM, Kasperzyk JL, Mucci LA, Giovannucci E, Price A, Wolk A, Håkansson N, Fall K, Andersson SO, Andrén O
Dietary fatty acid intake and prostate cancer survival in Örebro County, Sweden.
Am J Epidemiol. 2012 Aug 1;176(3):240-52.

Fradet V, Cheng I, Casey G, Witte JS.
Dietary omega-3 fatty acids, cyclooxygenase-2 genetic variation, and aggressive prostate cancer risk.
Clin Cancer Res. 2009 Apr 1;15(7):2559-66.

Edward Giovannucci, Eric B. Rimm, Graham A. Colditz, Meir J. Stampfer, Alberto Ascherio,
Chris C. Chute and Walter C. Willett
A Prospective Study of Dietary Fat and Risk of Prostate Cancer
JNCI J Natl Cancer Inst. Volume 85, Issue 19; Pp. 1571-1579.

C. Gómez Candela, L. M.ª Bermejo López and V. Loria Kohen
Importance of a balanced omega 6/omega 3 ratio for the maintenance
of health. Nutritional recommendations

Nutr Hosp. 2011;26(2):323-329.

Richard Nahin, PhD, MPH
Observational Studies and Secondary Data Analyses to Assess Outcomes in Complementary and Integrative Health Care
NCCAM Research Blog. 25 June, 2012

Neubronner J, Schuchardt JP, Kressel G, Merkel M, von Schacky C, Hahn A.
Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.
Eur J Clin Nutr. 2011 Feb;65(2):247-54.

Pettersson A, Kasperzyk JL, Kenfield SA, Richman EL, Chan JM, Willett WC, Stampfer MJ, Mucci LA, Giovannucci EL.
Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death.
Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):428-36.

Ivonne Ramírez-Silva, Salvador Villalpando, Jessica E Moreno-Saracho and Daniel Bernal-Medina
Fatty acids intake in the Mexican population. Results of the National Nutrition Survey 2006
Nutrition & Metabolism 2011, 8:33

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.

Schuchardt JP, Neubronner J, Kressel G, Merkel M, von Schacky C, Hahn A.
Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial.
Prostaglandins Leukot Essent Fatty Acids. 2011 Dec;85(6):381-6.

Simopoulos AP.
The importance of the ratio of omega-6/omega-3 essential fatty acids.
Biomed Pharmacother. 2002 Oct;56(8):365-79.

Artemis P. Simopoulos
The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases
Experimental Biology and Medicine  233:674-688 (2008)

Sorongon-Legaspi MK, Chua M, Sio MC, Morales M Jr.
Blood level omega-3 Fatty acids as risk determinant molecular biomarker for prostate cancer.
Prostate Cancer. 2013;2013:875615.

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.

Torfadottir JE, Steingrimsdottir L, Mucci L, Aspelund T, Kasperzyk JL, Olafsson O, Fall K, et al
Milk intake in early life and risk of advanced prostate cancer.
Am J Epidemiol. 2012 Jan 15;175(2):144-53. .

Torfadottir JE, Valdimarsdottir UA, Mucci L, Stampfer M, Kasperzyk JL, Fall K, Tryggvadottir L et al
Rye bread consumption in early life and reduced risk of advanced prostate cancer.
Cancer Causes Control. 2012 Jun;23(6):941-50.

Torfadottir JE, Valdimarsdottir UA, Mucci LA, Kasperzyk JL, Fall K, Tryggvadottir L, et al
Consumption of fish products across the lifespan and prostate cancer risk.
PLoS One. 2013 Apr 17;8(4):e59799.

P.J. van Jaarsveld, C.M. Smuts, H.Y. Tichelaar, M. Kruger, C.J. Lombard, A.J.S. Benadé
The influence of different ratios and dosages of an ω6:ω3 fatty acid supplement on the lipoprotein cholesterol and fatty acid profile in nonhuman primates on a western atherogenic diet
Nutrition Research. 17(11-12); Nov-Dec 1997: 1733-1747

Vasuki Wijendran and K.C. Hayes
Annual Review of Nutrition. July 2004; 24: 597-615

Yehuda S, Carasso RL.
Modulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio.
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10345-9.

Yehuda S, Brandys Y, Blumenfeld A, Mostofsky DI.
Essential fatty acid preparation reduces cholesterol and fatty acids in rat cortex.
Int J Neurosci. 1996 Sep;86(3-4):249-56.

Yehuda S, Rabinovtz S, Carasso RL, Mostofsky DI.
Essential fatty acids preparation (SR-3) improves Alzheimer’s patients quality of life.
Int J Neurosci. 1996 Nov;87(3-4):141-9.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

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