EPA Effectiveness COX 2 Inhibitor Colorectal Polyp Prevention

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March 19, 2010

Clinical trial finds EPA's effectiveness approaches that of COX-2 inhibitor in colorectal polyp prevention

Clinical trial finds EPA's effectiveness approaches that of COX-2 inhibitor in colorectal polyp prevention

Colorectal polyps, while benign most of the time, can become cancerous tumors. Individuals with familial adenomatous polyposis (FAP) possess a genetic mutation that results in the development of multiple polyps and a greatly increased risk of colorectal cancer. Randomized trials have demonstrated a colorectal cancer-protective effect for the nonsteroidal anti-inflammatory sunlindac and the COX-2 inhibitors celecoxib and rofecoxib in FAP patients. However, COX-2 inhibitors are associated with cardiovascular toxicity in older users and may not be entirely safe in younger patients as well.

A randomized, double-blinded trial, described in an article published online on March 18, 2010 in the journal Gut, included 55 men and women with FAP who had undergone removal of their colons to prevent the development of colorectal cancer. Participants received two capsules twice daily of enteric-coated eicosapentaenoic acid free fatty acid (EPA-FFA) or placebo capsules for 6 months. The omega-3 fatty acid EPA has been shown to have an anticancer activity in cultured colorectal cancer cells and in other studies.

Subjects underwent endoscopic examination of the rectum at the beginning of the trial and at the conclusion of the treatment period, during which the number and size of polyps in a defined area were measured. There was a 2.6 fold increase in mucosal EPA levels in those who received the free fatty acid compared with the placebo. While the number of polyps in both groups was similar at baseline, they increased by 9.7 percent in those who received a placebo while decreasing by 12.4 percent in the EPA group, resulting in an average 22.4 reduction in polyp number in the EPA group compared to the placebo group. Polyp size, as assessed by the sum of polyp diameters, increased by 17.2 percent among those who received a placebo and decreased by 12.6 percent in the EPA group, which represents an average 29.8% decrease in the group that received EPA compared with the placebo group.

The authors remark that the reduction in the number and size of polyps in a short intervention period suggests that the activity elicited by EPA consists of a combination of regression of existing polyps and prevention of new growth. They note that delivery of the fatty acid in enteric-coated capsules could explain the absence of minor upper gastrointestinal effects in the current trial's participants, which have been reported with prolonged use of omega-3 polyunsaturated fatty acids.

The study shares similar methodology with a trial involving the COX-2 inhibitor celecoxib, which also documented a decrease in polyp number among those who received active treatment. "EPA-FFA has chemopreventative efficacy in FAP, to a degree similar to that previously observed with selective cyclo-oxygenase-2 inhibitors," the authors conclude. "EPA holds promise as a colorectal cancer chemoprevention agent with a favorable safety profile."

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Health Concern Life Extension Highlight

Colorectal cancer

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) supplementation prior to colorectal cancer surgery improves the immune response and decreases the infection rate, improving patients’ outcome (Braga M et al 2002). In advanced cancer patients, EPA at doses of 18 grams is well tolerated and improves survival (Barber MD et al 2001; Burns CP et al 1999). Diets rich in omega-3 fatty acids decrease both the initiation and promotion of colon cancer (Kontogiannea M et al 2000). EPA prevents tumor cells from binding to healthy cells, as in blood vessels (Kontogiannea M et al 2000), and thus inhibits the development of liver metastasis (in animals) (Iwamoto S et al 1998). An omega-6 to omega-3 ratio of 2.5:1 reduced rectal cell proliferation in patients with colorectal cancer (Simopoulos AP 2002).

The EPIC study performed in 23 centers in 10 European countries found that high fish consumption had a protective effect against colorectal cancer (Gonzalez CA 2006a). Dietary fish oil supplementation in patients with adenomatous polyps reduces rectal cell proliferation, a marker of cancer risk (Bartram HP et al 1995). In a double-blind study of 60 patients with sporadic adenomas, low-dose fish oil supplementation (2.5 grams, 5.1 grams, or 7.7 grams per day for 30 days) had normalizing effects on the abnormal rectal proliferation patterns associated with increased colon cancer risk (Anti M et al 1994).

Large doses of fish oil prevent tumor growth through a free radical-mediated mechanism, while more moderate doses hinder inflammation, angiogenesis, and Ras protein activity (Grimm H et al 2002; Collett ED et al 2001; McCarty MF 1996). Mild gastrointestinal symptoms such as belching, bloating, gas, diarrhea, and a fish-oil aftertaste occur in some patients (Bruera E et al 2003; Gogos CA et al 1998).

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