Researchers at Vanderbilt University Medical Center have found that eating omega-3 polyunsaturated fatty acids (PUFA) regularly can result in prevention of colon polyp formation. Previous research in human subjects on the link has been inconclusive, although animal research suggests that there is a link between inflammation and colon polyp formation.
It is important to detect and remove colon polyps as a way to prevent colon cancer. While colon polyps are slow growing and carry a low risk of turning into a malignancy, they do have a high frequency that increases with age and can result in a predisposition to colon cancer.
Women who ate marine-derived omega-3 PUFAs had a 33% reduced risk of colorectal adenomas (odds ratio = 0.67, P = .01). The women with a reduced risk ate at least 3 servings of fish in a single week. The intake of omega-3 PUFAs was also negatively correlated with levels of prostaglandin E2 production (P = .002). The omega-3 fatty acid result, curiously, was seen in women but not in men.
No link was found in either men or women who consumed omega-6 PUFAs. Men who received alpha-linolenic acid through their diet were found to have an increased risk of hyperplastic polyps (P = .03).
A single serving of fish is 3.5 ounces or about three-quarters of a cup, according to the American Heart Association. Fish high in omega-3 fatty acids including wild salmon, mackerel, trout, anchovies, sardines, and albacore tuna.
The Study Design
The case-controlled study followed 3166 polyp-free control subjects, and 2144 subjects with either adenomatous or hyperplastic polyp cases, as identified by a colonoscopy. All participants were part of the Tennessee Colorectal Polyp Study.
All subjects kept track of their PUFA consumption with a dietary intake questionnaire and 896 subjects were tested for urinary prostaglandin E2 metabolite, a biomarker of prostaglandin E2 production. Prostaglandin E2 is a proinflammatory metabolite that is linked to colon cancer progression.
About 90% of detected polyps are hyperplastic and benign. Adenomas make up 10% of polyps that are larger and have an approximately 10% chance of containing invasive cancer cells capable of malignancy.
The Link Between Omega-3s and Cancer
The authors conclude that the benefit that women see in including omega-3 PUFAs in their diet may be due to reduced prostaglandin E2 levels. Harvey Murff, MD and associate professor of medicine at Vanderbilt and colleagues believe that regular omega-3 fatty acid intake can reduce inflammation in the body and protect against polyp formation. Prostaglandin E2 has been linked to adenomas and polyps in colorectal cancer. The link between reduced polyps and lower prostaglandin E2 levels is important, because it suggests that the correlation between lower polyps and omega-3 fatty acid consumption is real. To validate the linkage the authors are currently conducting a trial that is looking at the effect of fish oil supplements on prostaglandin E2 production.
According to Dr. Murff, fish oil looks like it confers a similar beneficial effect as aspirin in reducing inflammation, thus protecting against polyp formation.
Dr. Murff speculated that the men in the study may not have reaped the benefits of omega-3 consumption because they may also ingest higher levels of omega-6 fatty acids. "Part of the reasons for the different findings may have been the result of background dietary differences between men and women."
Omega-6 fatty acids are found in red meat, grains, and corn and sunflower oil, and may counteract the benefit of omega-3 fatty acids. The relationship between omega-6 fatty acids and colorectal cancer is not clear. Animal studies, for example, do no consistently show an impact of omega-6 fatty acids on colorectal cancer risk.
Another reason, Dr. Murff speculated, is related to gender differences on desaturase enzymes. "Women are more likely to convert the 18 chain PUFA alpha-linolenic acid into EPA and DHA than men. As such, they may have a higher 'internal dose' than men," he explained.
The research team is now looking at biomarkers of fatty acid exposure to test whether different levels of EPA and DHA can be detected in men vs women. The laboratory is also looking at the relative intake of different fatty acids and their impact on "rectal epithelial cell markers of cell proliferation and apoptosis," according to Dr. Murff.
A follow up, randomized trial looking at the effect of fish oil supplements on surrogate markers of colorectal cancer is currently ongoing. There are other groups that are also asking questions about the effect of these supplements on colorectal cancer risk.
"A major unanswered question still remains, what is the appropriate dose of fish oil? Given the likely scenario that background n-6 PUFA consumption might mitigate fish oils effects and that the Western diet tends to consume 20 n-6 PUFA to every 1 n-3 PUFA, we may be greatly underdosing the supplements," said Dr. Murff. "More work is needed on determining what is the necessary dose of fish oil to achieve the desired antiinflammatory effects."
Whether fish intake or supplements similarly reduce colorectal cancer risk remains to be confirmed. There is data that suggests that fish intake is the better option.