Omega-3 Fatty Acid Protects Against Polyps

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Omega-3 Fatty Acid Protects Against Polyps

Fish oil (omega-3 fatty acids) have been shown effective in treating high levels of triglycerides and in preventing primary and secondary cardiovascular disease. Now comes a new study showing that the fatty acid found in fish oil (EPA) has shown promise in the prevention of colorectal cancer in patients with familial adenomatous polyposis. The study was a randomized study. Although the study was performed in patients with a genetic predisposition to colorectal cancer, the benefits might also extend to non-inherited, or sporadic, colon cancer. Here are the details from  MedPage:
An omega-3 polyunsaturated fatty acid significantly reduced both the number and size of rectal polyps in patients with familial adenomatous polyposis, a randomized trial found.
Six months of treatment with the free fatty acid formulation of eicosapentaenoic acid (EPA) led to a decrease in mean number of polyps from 4.13 at baseline to 3.61, a 12.4% decrease, according to Nicholas J. West, MBBS, of St. Mark’s Hospital in London, and colleagues.
In contrast, six months of placebo treatment resulted in an increase from 4.50 polyps at baseline to 5.05, which represented a 9.7% increase, the researchers reported online in Gut.
Familial adenomatous polyposis is an autosomal dominant disorder in which affected individuals are predisposed to colorectal cancer, and prophylactic removal of the colon is recommended.
In younger patients, the procedure generally undertaken is colectomy with ileorectal anastomosis, but the remnant of rectal tissue remains susceptible, so patients must undergo routine endoscopic surveillance.
In the past, patients also were given chemoprevention with cyclo-oxygenase (COX)-2 inhibitors, but the recognition that these drugs have cardiovascular toxicity limits their long-term use today.
Strong preclinical evidence suggests that certain polyunsaturated fatty acids are active against colorectal cancer, but typical fish oil supplements are associated with adverse effects such as dyspepsia.
So a new, enteric-coated, free fatty acid formulation which is released and absorbed primarily in the small intestine was used to evaluate the potential efficacy of EPA for prevention of colorectal cancer in post-colectomy patients.
A total of 55 adult patients with familial polyposis were randomized to receive 2 g EPA per day or placebo.
After six months the difference between the change in polyp number between the EPA and placebo groups was −1.06 (95% CI −1.78 to −0.35, P=0.005), with an overall decrease of 22.4% (95% CI 5.1 to 39.6%, P=0.012).
In addition, the sum of polyp diameters decreased by 12.6% in the EPA group and increased by 17.2% in the placebo group — an overall difference of 29.8% in polyp size (95% CI 3.6 to 56.1, P=0.027).
Video endoscopy determined that EPA treatment was associated with a modest improvement in the global rectal polyp burden (+0.09), compared to overall worsening with placebo (−0.34). The difference was statistically significant (P=0.011).
There also was a mean 2.6-fold increase in rectal mucosal EPA levels associated with the active treatment.
Two patients in the placebo group withdrew because of abdominal pain, nausea, and rash, while one patient in the EPA group withdrew because of nausea and epigastric discomfort.
The most common adverse event in both groups was diarrhea, which may reflect a post-colectomy lack of physiologic control of fecal water, the investigators suggested.
Nausea was reported by nine patients receiving EPA and by three receiving placebo.
Patients reported no bleeding episodes, and there were no serious adverse events attributable to the treatment.
The antineoplastic activity demonstrated in the study “is almost certainly a combination of regression of existing adenomas and prevention of de novo tumor growth,” the researchers concluded.
Comparison of these findings with those from previous studies of chemoprevention in familial polyposis with the COX-2 inhibitor celecoxib found that the magnitude of effect was “remarkably similar.”
The authors said the data also suggest a role for EPA in chemoprevention of sporadic colorectal neoplasia.
The mechanisms by which EPA inhibits neoplastic activity remain uncertain, although both COX-dependent and COX-independent mechanisms of action have been described, including antioxidant effects and alteration of T cell and colonocyte membrane ‘lipid raft’ functions.
Aside from antineoplastic activity, omega-3 polyunsaturated fatty acids have beneficial cardiovascular and antiplatelet properties.
“Therefore, it is possible that EPA [free fatty acid] treatment may combine [colorectal cancer] chemopreventative efficacy with cardiovascular benefits, which is a particularly attractive therapeutic strategy for middle-to-old age populations relevant to secondary prevention of sporadic colorectal neoplasia,” the investigators asserted.

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