Animal and human findings demand clinical research to define the fatty nutrients' preventive and therapeutic potential; results also affirm the dangers of Americans' excessive omega-6 intake
by Craig Weatherby

Omega-3s were the subject of several papers presented at the 2009 Annual Meeting of the American Association for Cancer Research (AACR).

Prior animal and human cell studies have produced predominantly positive preliminary indications for the anti-cancer potential of long-chain omega-3s found in fish.

And animal studies presented at the 2005 and 2008 AACR meetings by noted cancer researcher Elaine W. Hardman, Ph.D., showed the dangers of diets very low in omega-3s and very high in omega-6s - an imbalance that accelerated in America during the 1950s and has only gotten worse.

As Dr. Hardman said at the time, suppression of tumor growth has been seen in mice when omega-3s constituted as little as two percent of daily calories.

Depending on your calorie intake, this equals 1.5 to 2.5 grams (1,500 mg to 2,500 mg) of omega-3s. This is the amount in 6 oz of wild salmon, or several fish oil capsules.

It's clear that the most beneficial omega-3s are the long chain kind found only in fish oil and fortified eggs (DHA and EPA).

But animal studies show that the short-chain, plant-derived omega-3s abundant only in walnuts, cooking greens, flaxseed, and canola oil also curb growth of cancer.

Here's a quick summary of some key papers presented at the AACR meeting. All except one
a clinical trial in women to gauge whether dietary omega-3s end up in breast tissuewere conducted in rodents or on human and animal cells.

These positive results add to a fast-growing body of evidence that should compel further research, including clinical trials.

Taken together with supporting research, the steady flow of persuasive findings justify a greater public health push for increased omega-3 intake and corresponding cut in Americans' excessive omega-6 consumption.

Fish oil boosted Tamoxifen's breast-tumor-busting effects in mice
A team from Pennsylvania State University found that in mice, supplemental fish oil boosted Tamoxifen's tumor-growth-retarding effects substantially.

By the end of the eight-week-long experiment, 61 percent of rats treated with the combination of fish oil and Tamoxifen were tumor-free, compared to 41 percent of corn oil fed rats treated with the same dose of Tamoxifen.

(Corn oil consists almost entirely of omega-6 fatty acids, which are associated with greater tumor growth. The same is true of soy, safflower, sunflower, and cottonseed oils.)

The scientists reported seeing an approximate 40 percent reduction in the number and volume of tumors in the mice given fish oil plus Tamoxifen, compared to the rodents that received only Tamoxifen (Manni A et al. 2009).

As they wrote, these findings are especially significant for two reasons:
  1. Tamoxifen and Raloxifene are not effective against all estrogen-independent tumors. The researchers wanted to test omega-3s because of the known “cross-talk” between women's estrogen receptors and the PPAR-gamma cell receptor activated by omega-3s… an interaction which they believe may “down-regulate” processes responsible for the development of drug-resistant, estrogen-independent breast cancers.
  2. Tamoxifen and Raloxifene are both associated with significant risks of dangerous blood clots, so anything that allows dose reductions should also reduce these drugs' clot-related risks. (Coincidentally, omega-3s also possess significant anti-clotting powers.)
Human breast tumor cell study
Researchers from the University of Kansas Medical Center added omega-3 fish oil to cultured human breast cancer cells and found it “highly efficacious” in suppressing tumor growth (Kang K et al. 2009).

Clinical trial finds that fish oil supplements raise omega-3 levels in breast tissue
Researchers from Ohio State University have proven for the first time that women can raise the levels of omega-3s in their breast cells by taking fish oil supplements.

This seems very significant since, as the authors wrote, there is “evidence that fatty acid profiles influence mammary carcinogenesis… based upon findings derived from many in vitro and several rodent studies...” (In vitro studies are those conducted on cells or cell cultures).

And as they said, “In order to test the effects of these fatty acids on breast cancer in humans it will be necessary to define an optimal dosing regimen.”

They conducted a “dose-response” study in women at high risk for breast cancer, using four different doses of a highly concentrated omega-3 supplement: either 0.9, 2.7, 5.4, or 8.1 grams of omega-3s per day for six months.

Fasting blood samples were obtained monthly, along with breast fat samples at zero, three, and six months.

They measured the effects of the omega-3 regimen on the women's blood fat profiles, platelet function, and liver function at three and six months as measures of safety.

Diet records and questionnaires were used to estimate the women's overall dietary fat intakes, in order to allow the researchers to gauge the participants' overall omega-3 intakes.

As hoped, the results proved a dose-response effect for both of the two key omega-3s
DHA and EPAin the women's blood, with the largest rate of rise seen during the first month.

Supplementation produced similar time-dependent increases in omega-3 DHA levels in fatty breast tissue.

Unsurprisingly, the women with the highest DHA levels at the beginning of the study showed the smallest increases in blood and breast levels… presumably because their blood and breast tissue couldn't hold many more omega-3s.

Let's hope that someone follows up, since, as the Ohio State team wrote, “These data will enhance our ability to define an optimal dose for translational human studies that can objectively test the hypothesis that fish oil/omega-3s impact human breast carcinogenesis” (Yee LD et al. 2009).

Fish oil curbs breast tumor growth in mice
An international research team from Harvard Medical School, Korea, and the University of Pittsburgh noted that omega-3s are known to inhibit cancer growth and spread in animals and in human breast cells (Lim K et al. 2009).

To help find out exactly how fish fats do these things, they exposed mouse breast cancer cells to omega-3 DHAone of the two key omega-3s in fish oiland implanted breast cancer cells in mice bred to produce omega-3s from dietary omega-6 fats (Omega- 6 fats are known to promote tumor growth).

The results affirmed the anti-cancer effects of omega-3 DHA in animals and their cells, and shed more light on the ways in which omega-3s suppress cancer growth in those settings. The international team's findings echo earlier findings, which pointed to the ability of omega-3s to suppress several pro-inflammatory immune-system proteins and genetic switches (MMP, VGEF, Nf-kB, AP-1, COX-2, PGE-2).

As they wrote, “…utilization of omega-3s [from fish oil] may represent an effective and safe therapeutic approach for the chemoprevention and treatment of human breast cancer” (Lim K et al. 2009).

Omega-3s curb while omega-6s fuel prostate tumors in mice… twice
In the first of two related studies presented at the AACR Meeting, researchers from the University of Pittsburgh and Colorado State University set out to confirm that dietary omega-3s retard prostate tumors (Kelavkar UP et al. 2009).

They also sought to test whether proportional shifts in omega-3 and omega-6 intake would dampen the activity of the pro-inflammatory metabolic pathways proven to fuel prostate tumors.

As they noted, omega-3s are proven to curb growth of prostate tumors in animals and in cultured human prostate cells.

They injected mice with prostate cancer cells, and divided them into three groups fed the same diets except for fat content:
  1. Diet equal in omega-6s and omega-3s
  2. Diet high in omega-6s / Low in omega-3s
  3. Diet high in omega-3s / Low in omega-6s
The results were striking:
  • Tumors in the omega-6-diet fed mice grew fastest.
  • Tumor growth slowed sharply in mice that were switched to omega-3 diet from the omega-6 diet.
  • Tumors grew much faster when mice were switched to the omega-6 diet from the omega-3 diet.
  • Levels of apoptosis were higher in tumors from the omega-3 group, versus tumors from the omega-6 group. (Apoptosis is a kind of cellular “suicide” that cells are genetically programmed to performbut sometimes don't—when their DNA undergoes cancer-promoting mutations.)
  • Berquin IM, Edwards IJ, Chen YQ. Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett. 2008 Oct 8;269(2):363-77. Epub 2008 May 13. Review.
  • Gillet L et al. Dietary omega-3 polyunsaturated fatty acids inhibit the growth of androgen-independent prostate cancer [51].In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 April 18-22; Denver, CO.
  • Hardman WE. (n-3) fatty acids and cancer therapy. J Nutr. 2004 Dec;134(12 Suppl):3427S-3430S. Review.
  • Kang K et al. Pharmacokinetics, tissue distribution and anticancer activity of eicosapentaenoic acid and docosahexaenoic acid, two cancer chemopreventive omega-3 fatty acids [2916]. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 April 18-22; Denver, CO.
  • Lim K et al. NF-kB, Oxidative Stress, and Other Pathways in Cellular Drug Responses [3749]. Omega-3 polyunsaturated fatty acids suppress cell invasion, tumorigenicity, angiogenesis, and metastasis by inhibition of MMPs/VEGF through NF-kB and AP-1 signal in breast cancer. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 April 18-22; Denver, CO.
  • Manni A et al. Combination of fish oil and Tamoxifen is superior to Tamoxifen alone for breast cancer prevention.[5034] In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 April 18-22; Denver, CO.
  • Kelavkar UP et al. Prostate tumor growth can be modulated by dietarily targeting the 15-lipoxygenase (LO)-1 and cyclooxygenase (COX)-2 enzymes [2963]. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 April 18-22; Denver, CO.
  • Yee LD et al. A dose response study of omega 3 fatty acids in women at high risk for breast cancer [2994].In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 April 18-22; Denver, CO