Fish Oil May Lower Rectal Polyp Burden in FAP

LONDON — A small, randomized trial suggests that fish oil given in tablet form as eicosapentaenoic acid may have chemopreventive effects, reducing the number and size of precancerous rectal polyps in patients with familial adenomatous polyposis.

The theory that this approach may have benefits in retarding cell proliferation has been tested in a number of other settings, including prevention of pancreatic, kidney, and esophageal cancers. But data on free fatty acid supplementation in the setting of familial adenomatous polyposis (FAP) have generally been confined to animal studies and anecdotal patient reports.

The new study was reported by Dr. N.J. West of St. Mark's Hospital Harrow, England, at the 13th World Congress of Gastroenterology. The goal was to examine whether eicosapentaenoic acid (EPA) supplementation reduced polyp burden in the setting of FAP, as assessed by blinded outside endoscopists.

The researchers randomized a total of 55 patients into two groups: EPA (28 patients who took a 500-mg capsule twice daily) or placebo (27 patients). All participants first underwent sigmoidoscopy, in which a focal area of rectum was tattooed for identification of baseline polyp number and size by endoscopists blinded to each subject's intended therapy. The patients also underwent rectal biopsies to determine the fatty acid content in their rectal tissue.

After 6 months, patients underwent a second blinded endoscopy, and the results “were highly statistically significant” in favor of EPA supplementation. EPA patients had a 12.6% reduction of their polyp burden in the targeted area. In contrast, placebo patients showed a 22.4% increase in their polyp count.

The difference between the groups amounted to an overall 24% relative retardation in polyp growth with EPA supplementation. Moreover, the blinded endoscopists found a 30% smaller mean polyp size in patients receiving the fish oil. In addition, EPA levels in the rectal mucosa increased by 159% in the EPA group, compared with the placebo group.

“Compared to placebo, EPA decreased the polyp burden in treated patients and decreased the polyp size at 6 months. The treatment was safe and well tolerated, and may deserve serious consideration as an alternative therapy for FAP,” Dr. West concluded.

Dr. Douglas K. Rex commented in an interview that “sulindac remains the cornerstone of chemoprevention in FAP. Celecoxib is an alternative when there is low cardiac risk and high risk of GI toxicity from NSAIDs. Fish oil is attractive because of its low risk profile, and it could be offered to FAP patients for this reason pending the results of additional studies of efficacy.”

“Endoscopists should remember that no chemopreventive treatment replaces endoscopic monitoring in FAP, and no chemopreventive therapy clearly prevents cancer in FAP,” cautioned Dr. Rex, who is distinguished professor of medicine at Indiana University, Indianapolis, and director of endoscopy at Indiana University Hospital.

Dr. West acknowledged that this trial was limited by its size and duration, and thus could not show whether changes in polyp burden following EPA could actually reduce the likelihood of future colorectal cancer. Nor could it answer the question of how long such therapy might need to be delivered to prevent colorectal cancer.

But he noted that EPA supplementation involves fewer side effects (and less expense) than was seen in trials of the COX-2 inhibitor celecoxib, which has been associated with adverse inflammatory and cardiovascular effects. “Free fatty acid has the potential to serve as an important therapeutic option if these results can be borne out by larger trials,” he observed.

Disclosures: The study is an offshoot of a British polyp registry that was developed, with support from the National Cancer Institute, Pfizer, and Ilex Oncology, to conduct clinical trials of agents of interest.