Diets High in Long-chain Omega-3 Fatty Acids Shown to Help Prevent Cox-2 Sependent Adenocarcinomas

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Saint Luke’s Mid America Heart Institute research study finds marked benefits for cancer prevention with a higher intake of fatty fish.

A new research review published today will once again have people asking for a second helping of wild Alaskan salmon at the dinner table. While several other studies have recently challenged the long-held belief of the benefits of a diet high in omega-3 fatty acids, this new study led by Saint Luke’s Mid America Heart Institute cardiovascular research scientist James J. DiNicolantonio, PharmD, cites compelling evidence that eating the right kinds of fatty fish, in the right quantity, and prepared the right way, can in fact help prevent the body’s development of adenocarcinomas, a common type of cancerous tumor. A high proportion of the cancers arising in the breast, prostate, pancreas, colon, and the rest of the gastrointestinal tracts are adenocarcinomas.

The review, titled “A Higher Dietary Ration of Long-Chain Omega-3 to Total Omega-6 Fatty Acids for Prevention of COX-2-Dependent Adenocarcinomas,” is being published in the journal Nutrition and Cancer. The authors first cite evidence that the recently-demonstrated ability of daily low-dose aspirin to decrease risk for adenocarcinomas is attributable to its ability to modestly decrease the activity of cyclooxygenase-2 (cox-2), an enzyme which contributes importantly to the genesis and progression of adenocarcinomas. They then propose that an ample dietary intake of omega-3 fats—the type prominent in fatty fish—could also be expected to oppose cox-2 activity, and thereby reduce risk for adenocarcinomas.

However, some epidemiological studies correlating fish consumption with subsequent cancer risk have failed to show a protective effect of fish consumption; this is particularly true for “meta-analyses” lumping together the results of a number of separate studies. The authors propose that this reflects the fact that in many populations, fish consumption is too sporadic to achieve the tissue levels of omega-3 needed for cancer prevention. They, therefore, focus on studies in which a significant proportion of the surveyed population eats fatty fish several times weekly—or take fish oil supplements on a regular basis—and find that the data from these studies is largely supportive of the cancer-preventive potential of fish oil.

The authors cite the following reasons why many studies have failed to correlate habitual fish consumption with cancer risk:

  • Relatively low fish intake among the high-intake category. According to the study, the average daily American intake of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is said to be only about 100 mg. However, it likely requires omega-3 intakes in excess of a gram daily to achieve functionally significant effects on cox-2 activity. Therefore, in studies where even the heavier fish consumers are unlikely to achieve the intakes required to modulate cox-2 activity, cancer prevention could not be expected.
  • High concurrent intake of omega-6 rich oils. Many diets are rich in polyunsaturated oils (safflower oil, corn oil, cottonseed oil, etc.) providing omega-6 fatty acids. Since omega-6 fats compete with omega-3 fats for access to cox-2, a high intake of omega-6 could be expected to increase the intake of omega-3 needed for cancer protection. Mediterranean populations in which olive oil— low in omega-6—is the staple dietary fat are therefore more likely to demonstrate a protective effect of frequent fish consumption, as the authors document.
  • Predominant consumption of lean fish, low in omega-3. Some studies surveyed by the authors conclude that intake of fatty fish correlates with cancer protection, whereas intake of lean fish does not. This is consistent with the view that it is the omega-3 fats in fish that are primarily responsible for the cancer protection afforded by fish consumption.
  • Farmed fish often has a relatively high omega-6/omega-3 ratio. Because they are fed with grains, farmed fish—like many marketed tilapia and salmon—tend to have a higher omega-6/omega-3 ratio than wild fish. The long-chain omega-3s in fish are not synthesized de novo but rather come from the unicellular organisms that they eat. Therefore, the diet they are fed when being farmed does not help produce the same omega-3s that occur naturally in the wild.
  • Preserved fish often contain mutagens such as nitrosamines. In some studies, which the authors surveyed—particularly some Asian studies—salt-preserved fish was the predominant type of fish consumed. Salt-preserved fish, as opposed to fish that is fresh or frozen, commonly contains mutagens produced by contaminating bacteria. Hence, such mutagens (not the salt per se) could be expected to offset any benefit of concurrently consumed omega-3.
  • Fried fish has an increased omega-6/omega-3 ratio and fish cooked at high-heat (e.g. frying) has heterocyclic amines and other mutagens. Frying fish, as opposed to baking or boiling it, can reduce the total omega-3 content while notably increasing the omega-6/omega-3 ratio of the fish if a polyunsaturated oil is used in frying. Additionally, high-temperature cooking of fish, such as frying, can promote production of mutagenic heterocyclic amines, which can cause changes in DNA that may increase the risk of cancer.

The authors therefore emphasize that not only the amount of fish consumed daily, but also the nature of this fish, and how it is preserved or cooked, can have a major impact on the potential of dietary fish to lower cancer risk.

“An easy way to see the benefit of omega-3 is to look at Italy,” Dr. DiNicolantonio said. “The staple oil used in cooking and as a salad dressing in Italy is olive oil, which is quite low in omega-6. Meanwhile, fish—high in omega-3—is a staple food in the Italian diet, and this fish is rarely salt-preserved or fried. In Italians studies, subjects who consumed fish at least twice weekly as compared to those who ate fish less than once a week, were found to be at a significantly lower risk for a number of cancers, including ovarian, endometrial, pharyngeal, esophageal, gastric, colonic, rectal, and pancreatic.”

The authors also focus on several recent studies in which regular consumption of fish oil is correlated with lower subsequent cancer risk. These studies have reported lower risks for colorectal, breast, and advanced prostate cancer in those taking such supplements. And a recent study from the University of Washington, which estimated total omega-3 intakes of its subjects from both fish and from supplements, found that a high omega-3 intake was associated with a 23 percent reduction in total cancer mortality. Indeed, mortality from all causes was significantly lower in those with higher omega-3 intakes.

The authors also noted that cox-2 is significantly expressed in pre-malignant and early stage adenocarcinomas, but expression is sometimes lost as cancers mature. This may be why cox-2 inhibition (via increased omega-3 intake) seems to have greater potential for cancer prevention, than for cancer therapy.

The review was authored by Saint Luke’s leading cardiovascular research scientist Dr. James J. DiNicolantonio, PharmD; as well as Mark F. McCarty, BA, Catalytic Longevity; Subhankar Chatterjee, MBBS Student, R.G. Kar Medical College & Hospital, Kolkata, India; Carl J. Lavie, M.D., John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, Louisiana and Pennington Biomedical Research Center, Baton Rouge, Louisiana; and James H. O’Keefe, M.D., Mid America Heart Institute at Saint Luke’s Hospital of Kansas City and the University of Missouri-Kansas City, Kansas City, Missouri.

The original paper may be found at To learn more about Dr. DiNicolantonio, visit

About Saint Luke’s Mid America Heart Institute
Saint Luke’s Mid America Heart Institute, a member of Saint Luke’s Health System and a teaching affiliate of the University of Missouri-Kansas City, is one of the preeminent cardiovascular programs in the country. Its legacy of innovation began more than 25 years ago when it opened as the nation’s first heart hospital. Since then, the Heart Institute has earned a world-wide reputation for excellence in the treatment of heart disease, including interventional cardiology, cardiovascular surgery, imaging, heart failure, transplant, heart disease prevention, women’s heart disease, electrophysiology, outcomes research, and health economics. With more than 50 full-time board-certified cardiovascular specialists on staff, the Heart Institute offers one of the largest heart failure/heart transplant programs in the country, has the largest experience with transcatheter aortic valve replacement in the Midwest, and is a global teaching site for the newest approaches to opening challenging blocked arteries using minimally invasive techniques.

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