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Omega-3 DHA's Promising Anti-Cancer Power
Landmark study reveals that a byproduct of dietary omega-3 DHA helps curb tumor growth
4/8/2013
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By Craig Weatherby
 
Evidence that omega-3s from fish help prevent and hinder cancer – and that omega-6 fats encourage cancer – continues to mount.
 
Neither omega-3 pills nor omega-3-rich diets are proven preventive agents or miracle cures for cancer.
 
Instead, growing research indicates that diets high in omega-3s from fish – and low in omega-6s from vegetable oils (compared with the standard American diet) – make it harder for cancer to start, grow, and spread.
 
Fish fats’ anti-inflammatory powers probably play a major role in their apparent ability to help curb cancer development and growth.
 
A team of Italian evidence-reviewers put it this way:
“Inflammation dictates tumor initiation, progression and growth. Omega-3 fatty acids exert anti-inflammatory effects, and ... limited evidence suggests a role for omega-3 fatty acid supplementation in cancer prevention ...” (Laviano A et al. 2013)
 
But other anti-cancer properties of omega-3s continue to be uncovered, as we reported in 2005: “More Evidence That Fish Oil Inhibits Breast Cancer”.
 
For more of our coverage, visit “Omega-3s vs. Breast Cancer”, “Omega-3s May Help Curb Skin Cancer”, “Can Fish Curb Colon Cancer?” and related articles in the Omega-3s & Immunity section of our news archive.
 
Back in 1998, a nascent class of drugs designed to block the growth of blood vessels supplying tumors made huge waves: see “A Cautious Awe Greets Drugs That Eradicate Tumors in Mice”.
 
Formation of new blood vessels in the body is called angiogenesis … and certain anti- angiogenesis agents (drugs or nutrients) can stop or slow it. The Times’ 1998 report got ahead of the science, but its basic premise has been partially redeemed by the arrival of working anti-angiogenesis cancer drugs.
 
And researchers continue to explore the promise of anti-angiogenesis drugs in cancer and other conditions, with some stunning successes … especially with regard to “wet” macular degeneration.
 
Omega-3 DHA displays anti-angiogenesis effects
Now, a team of scientists from UC Davis and Harvard University reports that a metabolite (breakdown product) of omega-3 DHA cuts off the supply of oxygen and nutrients that fuels tumor growth and the spread of cancer (Zhang G et al. 2013).
 
The metabolite is called EPD (epoxy docosapentaenoic acid), a compound we make from omega-3 DHA.
 
Along with EPA, DHA is one of the two major omega-3s found in fish oil and all human cells.
 
A third omega-3, called DPA (docosapentaenoic acid), forms part of the EDP molecule, and is revealing its own strong health benefits.
 
Earlier the UC Davis scientists found that EDP inhibits the formation of new blood vessels … a normal, healthy process called “angiogenesis”.
 
Angiogenesis is essential to wound repair as well as growth and development … but tumors grow and spread by hijacking this process.
 
The UC/Harvard team found that EDP curbed angiogenesis in mice, and thereby reduced the growth and spread (metastasis) of tumors.
 
A safer, complementary anti-angiogenesis drug?
EDP starves tumors by inhibiting two key promoters of angiogenesis, called vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2).
 
In laboratory cultures, EDP also suppresses the endothelial cell migration needed for new blood vessels.
 
And, EDP likely works more safely than current anti-angiogenesis cancer drugs … whose side effects include bleeding problems, arterial clots (with resultant stroke or heart attack), hypertension, and protein in the urine. (NCI 2013)
 
EDP offers an advantage over angiogenesis inhibitor drugs that target the VEGF-VEGFR2 pathway, which raise patients’ risk for high blood pressure.
 
Because EDPs widen the blood vessels, a drug based on the UC Davis researchers’ discovery shouldn’t raise people’s hypertension risks.
 
They plan future studies to determine whether EDP can be stabilized and safely and effectively combined with other anti-angiogenesis cancer drugs.
 
Omega-3-derived EDPs are broken down in the body by the enzyme soluble epoxide hydrolase (sEHI).
 
Why does this matter? UC Davis researchers determined that the addition of sEHI stabilized EDP in circulating blood thereby producing EDPs’ anti-tumor effects.
 
The FDA-approved anti-cancer drugs sorafenib and regorafenib are also potent sEHIs. “It may be possible to improve the efficacy of these anti-cancer drugs by combining them with a diet high in omega-3 and low in omega-6 fatty acids,” Hammock said.
 
The researchers also found that a metabolite of arachidonic acid (ARA), an omega-6 fatty acid, has the opposite effect of EDP. The ARA metabolite, epoxyeicosatrienoic acids (EETs), slightly increases angiogenesis and tumor progression in mice.
 
“Our results designate EDPs and EETs as unique mediators of an angiogenic switch to regulate tumorigenesis,” Ferrara said. "They also implicate a novel mechanistic linkage between omega-3 and omega-6 fatty acids and cancers.”
 
 
Sources
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  • Murphy RA, Mourtzakis M, Mazurak VC. n-3 polyunsaturated fatty acids: the potential role for supplementation in cancer. Curr Opin Clin Nutr Metab Care. 2012 May;15(3):246-51. doi: 10.1097/MCO.0b013e328351c32f. Review.
  • National Cancer Institute (NCI). Angiogenesis Inhibitors. Accessed April 7, 2013 at http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors
  • Wu M, Harvey KA, Ruzmetov N, Welch ZR, Sech L, Jackson K, Stillwell W, Zaloga GP, Siddiqui RA. Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int J Cancer. 2005 Nov 10;117(3):340-8.
  • Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY, Stephen Lee KS, Wettersten HI, Ulu A, Hu X, Tam S, Hwang SH, Ingham ES, Kieran MW, Weiss RH, Ferrara KW, Hammock BD. Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci U S A. 2013 Apr 3. [Epub ahead of print]
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