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Health News Archive 37 - Colon Health (con't)
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Probiotics Equally Effective Against IBD When Alive or Dead

Researchers at the University of California, San Diego and the Shaare Zedek Medical Center in Jerusalem, Israel report that probiotics, the “friendly” bacteria used to make yogurt and kefir, do not have to be living to provide benefits. Experts had previously believed that the viability of these probiotic microorganisms was essential to their ability to help treat several conditions, such as inflammatory bowel disease (IBD) and allergies. The study was published in the February 2004 issue of Gastroenterology.

Senior author and professor of medicine at UCSD, Eyal Raz, MD, explained, “Our goal was to address whether the metabolic activity of probiotics was mandatory for their protective effect.“ The researchers radiated probiotics to reduce their metabolic activity to a minimum, and administered the inactive bacteria to mice in whom colitis, which is similar to human inflammatory bowel disease, had been induced. Another group of colitis-induced mice received nonirradiated probiotics. It was discovered that both nonviable and viable (live) probiotics effectively treated the colitis.

Prior research had used heat to inactivate probiotics, but this destroyed the bacteria's cellular structure as well as their benefits. The DNA found in each cell stimulates the innate immune system, providing an anti-inflammatory effect. In another experiment, Raz's team found that the immune molecule toll-like receptor 9 needs to be activated for the probiotics to provide their benefits against colitis in this mouse model.

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Fiber plus Vitamin D Reduces Colon Cancer Risk

In a study that has been called one of the most comprehensive to date on colon cancer risk, researchers from Harvard University, Veterans Affairs and the National Cancer Institute have found that the consumption of Vitamin D and fiber are associated with a lower risk of serious colon polyps, which can be a precursor to colon cancer. The study was published in the December 10 2003 issue of the Journal of the American Medical Association (JAMA).

The study involved 3,121 subjects who were examined at 13 VA Medical Centers around the country between 1994 and 1997. Questionnaires were administered to determine dietary intake, and medical history was reviewed.  All subjects underwent a colonoscopy, where 329 cases of advanced neoplasia, defined as a polyp of 10 millimeters or more, a villous adenoma (often a precursor of of adenocarcinoma), adenoma with high grade dysplasia, or invasive cancer were found.

Several common factors were noted for the men in the study, including fiber, Vitamin D, aspirin, smoking and alcohol use and family history.  Men who consumed more than 4 grams of fiber per day, and over 645 international units of vitamin D per day demonstrated a significantly reduced risk of developing serious colon polyps. Taking aspirin on a daily basis lowered the risk by one-third. Having a first degree relative with colon cancer, smoking, and moderate to heavy alcohol use emerged as factors that increased risk. A separate analysis that studied those whose worst lesions were hyperplastic polyps (small benign polyps) produced similar findings.

Lead investigator and chief of gastroenterology at the Portland VA Medical Center and Oregon Health and Science University, David Lieberman, MD, stated, "The finding that may surprise the scientific community is the vitamin D data . . . . These data support relatively simple and safe recommendations that may reduce the risk of colon cancer. Stop smoking, reduce alcohol consumption, take a multivitamin, exercise regularly, and consume vitamin D, calcium and fiber in your diet."

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Calcium and Vitamin D Work Together in Colon Cancer Prevention

A report published in the December 2003 Journal of the National Cancer Institute detailed the findings of the Dartmouth Medical School in Lebanon, New Hampshire that calcium and vitamin D work together to reduce colorectal cancer risk. In past studies, vitamin D and calcium separately protected against the development of abnormal growths in the large intestine. These findings suggest that these two nutrients work synergistically in protecting the colon just as they do in protecting the bones.

The study analyzed data provided by 803 participants in the Calcium Polyp Prevention Study, which found that supplementation with 1200 milligrams calcium a day was associated with a lower risk of recurrence of colorectal adenomas, or polyps, which can be a precursor of colorectal cancer.

Researchers, led by Maria V Grau, MD, found that calcium supplements reduced the risk of polyp recurrence only among individuals whose vitamin D levels were higher than the median at the study's onset.  Conversely, serum vitamin D levels were associated with a lower risk of polyps reoccurring only among participants who were taking calcium supplements. 

In an accompanying editorial in the Journal of the National Cancer Institute, Dr. Elizabeth T Jacobs and colleagues speculate that the presence of adequate calcium might allow for the diversion of 1,25-hydroxyvitamin D3 to antitumor activities. 1,25-hydroxyvitamin D3 is produced from 25-hydroxyvitamin D, and is the form of vitamin D found to have antiproliferative effects in colon cancer.

The researchers concluded that the findings "provide a strong indication that vitamin D and calcium have a joint antineoplastic effect in the large bowel."

Source: J Natl Cancer Inst. 2003;95:1736-1737,1765-1771.

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Green Tea Effective in Preventing Colon Tumors

In research conducted at the Linus Pauling Institute at Oregon State University published in the February 2003 issue of the journal Carcinogenesis, it was found that both green tea and white tea reduced colon polyps as well as the nonsteroidal anti-inflammatory drug (NSAID) sulindac, and that a combination of sulindac and white tea reduced polyp formation even more. Previous research has shown that sulindac can cut polyp formation by one half. The research was funded by the National Cancer Institute.

In the Linus Pauling Institute study, mice bred to develop intestinal tumors were given drinking water to which was added green tea, white tea, sulindac, a combination of white tea and sulindac or plain water for twelve weeks. At the study's conclusion, the mice who received green tea had 17 tumors compared to 30 tumors in the control group. White tea further reduced polyp formation to 13, and a combination of the tea with sulindac resulted in a finding of only 6 polyps. Because NSAIDs such as sulindac can have side effects, an agent that increases the efficacy of a lower dose would be valuable.

Coauthor Gayle A Orner of Oregon State University wrote, "Tea is one of the most widely consumed beverages in the world, and recent upswings in the sales of green tea in the United States can be attributed to reports of potential health benefits against cancer and other chronic diseases. Teas exert significant protective effects in experimental animal models of skin, lung, esophageal, gastric, hepatic, small intestinal, pancreatic, colon, bladder and mammary cancer . . . These are pretty exciting results. What's especially significant is that as far as we can tell consumption of tea has none of the side-effects of NSAIDs, which can be severe, including bleeding, ulcers and even death."

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Folic Acid Supplements Lower Risk for Colon Cancer

The August 2002 issue of the journal, Gut published a study conducted in Ireland which showed that folic acid supplementation can help prevent the increased mucosal cell proliferation in individuals at risk of colon cancer. 

Twenty patients with recurrent adenomatous polyps of the colon, which have the possibility of becoming cancerous, received two milligrams folic acid per day or a placebo for 12 weeks. Rectal biopsy samples were taken from the participants before supplementation, and at four, twelve and eighteen weeks in order to examine cell proliferation. Blood samples were also taken at these examinations. The patients completed three-day dietary questionnaires at the study's onset and following supplementation, and the researchers calculated the amount and type of food consumed.

The researchers found that although mucosal cell proliferation between the groups was similar at the beginning of the study, the group receiving folic acid experienced a reduction in proliferation by the study's conclusion. The most significant reduction took place at the upper aspect of the crypt. Crypts are the indentations in the walls of the colon in which cells grow and replicate, with oldest cells existing at the top. Animal studies have shown that changes in colony mucosal crypt cells are related to changes in tumor risk.

The researchers speculate that increasing folic acid may help to protect DNA through its involvement in methylation and its prevention of strand breaks. A deficiency of folate may also impair DNA repair in the mucosa of the colon and lead to chromosomal abnormalities at fragile sites.

The researchers conclude that folic acid supplementation can regulate colonic mucosa cell proliferation in patients at risk of colon cancer and note that the effect of the supplements may persist after they are discontinued.

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Vitamin E Boosts Immune Function in Colon Cancer Patients

A study published in the June 2002 issue of Clinical Cancer Research found an increase in T helper 1 cytokine production in patients with advanced colorectal cancer who were given Vitamin E. Researchers at the Karolinska Institute in Sweden hypothesized that supplementation with vitamin E could boost immune function in patients with advanced cancer by diminishing the oxidative stress arising from the chronic inflammation seen in this population. Humans and animals with advanced cancer show signs of immune dysfunction including decreased T-cell proliferation, reduced CD4:CD8 ratios, and decreased production of T helper 1 cytokines, which have been correlated with lower survival.

Twelve patients with colorectal cancer were given supplements containing 750 milligrams vitamin E, 60 micrograms selenium and 90 milligrams vitamin C, which was consumed in divided doses for fifteen days. Patients were given physical examinations at the beginning and conclusion of the study, and blood samples were collected. No side effects from the supplements were reported.

Plasma levels of vitamin E more than doubled as a result of the treatment, and the ratio of CD4 to CD8 ratios increased as well. Diminished CD4 counts have been correlated with late-stage colorectal cancer and may be indicative of immunosuppression. Treatment with vitamin E enabled T cells to more readily produce the T helper 1 cytokines interferon-gamma and interleukin 2. In ten of the twelve patients an average increase of 22% in the amount of T-cells that produced interleukin 2 was observed following vitamin treatment compared to pretreatment levels. Naive T helper cells exhibited a greater response than memory T cells. Because of the lack of an increase in interleukin-10 production observed, the authors speculate that the mechanism of action of vitamin E may be other than that of scavenging free radicals.

Source: Clinical Cancer Research; June 2002 (http://clincancerres.aacrjournals.org/)

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CLA Inhibits Prostate and Colorectal Cancer Growth

In research published in the March 28 2002 issue of the journal Cancer Letters, scientists from Harvard Medical School reported that commercially available conjugated linoleic acid, or CLA, inhibited the growth of cancer in one human prostate and two human colorectal cancer cell lines. One CLA isomer showed the greatest effectiveness against colorectal cancer while both CLA isomers were moderately effective at inhibiting prostate cancer. The t10,c12 isomer was found to cause caspase-dependent apoptosis in the prostate cancer cells and in one of the colorectal cancer cell lines.

CLA is part of the omega-6 fatty acid family, but its mechanism of action is similar to that of omega-3 fatty acids.

Assistant Professor of Surgery at Beth Israel Deaconess Medical Center and Harvard Medical School, and coauthor of the study, Dr John Palombo, commented, "There are specific isomers within CLA that exhibit an inhibitory effect on cancer proliferation . . . These in vitro results indicate that the cancer-reducing properties of CLA or its constituent isomers are not equivalent. The net reduction in cancer cell proliferation appears to be dependent upon the type and concentration of CLA isomer used. A better understanding of novel CLA preparations and their constituent isomers is required before initiating intervention (human clinical) trials of CLA in patients undergoing treatment of colorectal and prostate cancer, as well as individuals at risk for these cancers."

The researchers state that CLA preparations may prove effective as chemopreventive supplements for patients diagnosed with prostate or colorectal cancer, or for those at risk of the disease. An additional boon is the absence of adverse effects that often occur with pharmaceutical agents.

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Fish Oil Significantly Reduces Crohn's Disease Relapse

Crohn's disease is characterized by periods of active disease interspersed with periods of remission.  Now researchers at the University of Bologna, Italy report that fish oils prevent relapses.  

Their experiment involved 78 patients with Crohn's disease who had been classified as having a high risk of relapse.  Half the patients were randomized to receive nine fish oil capsules daily, the other half received nine placebo capsules daily.  The fish oil capsules contained 500 mg of a marine lipid concentrate (40 percent eicosapentaenoic acid and 20 percent docosahexaenoic acid) and provided a total of 2.7 grams of n-3 fatty acids per day.  The capsules were enteric-coated so as to ensure that they dissolved in the small intestine instead of in the stomach and to minimize unpleasant side effect such as flatulence, heartburn, belching, and diarrhea.  

The results of the fish oil therapy were spectacular.  While 69 percent of the patients in the placebo control group had a relapse during the one-year study period, only 28 percent in the fish oil group did.  At the end of the one-year period, 59 percent of the patients in the fish oil group were still in remission as compared to only 26 percent in the placebo group.  The researchers conclude that fish oil therapy (with enteric-coated capsules) is effective in preventing relapses in patients with Crohn's disease in remission.  

NOTE: This study was supported in part by Tillotts Pharma of Switzerland, the manufacturer of the enteric-coated fish oil capsules.

Billuzzi, Andrea, et al.  Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease.  The New England Journal of Medicine, Vol. 334, No. 24, June 13, 1996, pp. 1557-60.

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