Folic acid supplementation could reduce colorectal cancer risk

Tuesday, May 10, 2016

A randomized trial reported online on April 13, 2016 in the Journal of Nutrition found improved folate-related biomarkers of cancer risk among patients who were given folic acid supplements subsequent to colorectal adenoma (polyp) removal. Polyps can be precursors of colorectal cancer and individuals who develop them are considered to be at increased risk of the disease. Polyps and their surrounding mucosa have been observed to have low folate levels compared with normal colonic mucosa.

According to authors Sharleen L. O'Reilly of Trinity College, Dublin and her colleagues at the University of Ulster, "Folate may exert a protective effect by enhancing genetic stability through 2 main pathways: preventing uracil misincorporation that leads to DNA strand breaks, and/or preventing diminished DNA methylation that causes altered gene expression."

The trial included 20 men and women who had colorectal polyps removed during colonoscopy. Participants were assigned to receive 600 micrograms folic acid or a placebo daily for six months. Repeat colonoscopies were performed after six months and colon cells from the site of excised polyps were evaluated for DNA changes. Blood and colon cell folate levels were measured before and after the treatment period.

Significant increases in serum and red blood cell folate levels and decreased plasma homocysteine levels occurred after six months among those who were given folic acid. In cells in the area of the colon adjacent to the location of the removed polyps, folate concentrations increased in those who received the vitamin, while slightly declining in the placebo group. (Folate concentrations in areas that were not near the polyp site remained the same in both groups.) Participants who received folic acid experienced a greater decline in markers of DNA damage at the site formerly adjacent to the polyps in comparison with the placebo. "That these areas persist after polypectomy in the absence of folate supplementation is consistent with a potentially carcinogenic field's causing the appearance of the polyp," the authors note. "These findings indicate that localized areas of folate depletion at sites adjacent to adenomatous polyps may respond to supplementation in a way likely to reduce mutagenesis."

"Our study, although limited by numbers, not only points toward improved folate status's exerting a beneficial effect on the health of colonocytes in critical regions in people at risk of developing colorectal cancer, but also strengthens the field cancerization hypothesis," they conclude.

In summary, the authors believe that folic acid may stabilize DNA structure and enhance healthy gene expression.

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Folic acid supplementation reduces colorectal adenoma risk
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An article appearing in the July 2013 issue of Cancer Prevention Research reports the outcome of a trial conducted in China which found a 50% average reduction in the risk of sporadic colorectal adenomas in older men and women supplemented with folic acid. Colorectal adenomas (polyps), while often benign, can be a precursor to colorectal cancer, with 90% of cases starting as adenomas.

Researchers at Shanghai Jiao-Tong University School of Medicine randomized 791 subjects between the ages of 50 and 80 years with no adenomas to receive 1 milligram (mg) folic acid per day or a supplement without folate for three years. Plasma folate levels were measured upon enrollment and at the end of the treatment period. Colonoscopies administered at the study's conclusion ascertained the location and size of all polyps, which were subsequently examined by a pathologist.

Colorectal adenomas were found in 30.7% of participants who received a placebo and 14.9% of the folic acid group. There was also a reduction in the risk of advanced adenomas among those who received folic acid. A greater risk of adenoma was observed among subjects in either group whose plasma folate levels were lower at the beginning of the study.

"Although several studies have suggested that high-dose folic acid might increase the recurrence and progression of colorectal cancer, only two participants in our folic acid group developed colorectal cancer during three years of follow-up and there was no significant difference with the control group," the authors write. "We believe that 1 mg/day folic acid supplementation is safe and has few side effects."

"Those with low plasma folate should be encouraged to take adequate supplements, and plasma folate should be elevated to an effective therapeutic level, which may reduce the incidence of colorectal adenoma," they conclude.

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Life Extension Magazine® May 2016 Issue Now Online

Life Extension Magazine®

On the cover

Omega-7: An overlooked fatty acid, by Cynthia Ronen


Green tea, by Henry Jenkins

Mediterranean herb guards vital liver functions, by Linda Nevis

Lactoferrin promotes healthy healing after cataract surgery, by Miles Mueller

Why the FDA is wrong about testosterone, by Craig Stamos

Early intervention delays aging, by Chase Falcon


As we see it: FDA suffers major legal defeat in federal court, by William Faloon

In the News

Superfoods: Garbanzo beans, by William Gamonski

Ask the Doctor: The most important blood tests available for assessing cardiovascular risk, by Scott Fogle, ND

Journal abstracts

Lactoferrin, green tea, milk thistle, omega-7 and testosterone

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Health Concern

Colorectal Cancer

As much as seventy percent of colon cancers are thought to be preventable through diet and lifestyle modification (Anand 2008). Factors such as diet, physical activity level, tobacco use, alcohol consumption and sleep patterns are associated with increased risk of colorectal cancers (Schernhammer 2003). Obesity and physical inactivity are known to increase biomarkers of inflammatory processes, such as fecal calprotectin and serum C-reactive protein (CRP); elevated levels of inflammation are linked with higher rates of colorectal cancer. Greater vegetable and fiber intake has been associated with reduced levels of fecal calprotectin, a marker of intestinal inflammation (Poullis 2004).

A colon cancer treatment or prevention plan should start with foundational lifestyle measures that include physical activity and a diet rich in plant foods; patients should also strive to attain a healthy body weight.

Homocysteine is an indirect marker for folate, B6 and B12 status. Homocysteine can be high when there is a deficiency in any of these B vitamins. Folate deficiency is associated with greater risk of developing colorectal cancers. In a large pooled analysis of data from 13 prospective studies including over 725,000 subjects, the highest quintile of folate intake was associated with a 15% reduced risk of colon cancer compared to the lowest quintile of intake (Kim 2010).

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