The role that inflammatory processes, such as those modulated by COX-1 and -2 have in colon cancer, may well be significant; in fact, several studies have demonstrated a definite inverse relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of colon cancer.18,19 In fact, this has led some authorities to recommend aspirin as a preventive. One of the proposed mechanisms of protection by NSAIDs is that, by inhibiting the action of the COX enzymes, production of potentially tumor-favoring prostaglandins is reduced. While it may be the case that the advent of specific COX-2 inhibitors will allow for benefit in this regard without the side effects (such as gastrointestinal bleeding and renal damage) of less-specific NSAIDs, there may be distinct advantages to taking a more broad anti-inflammatory approach that includes supplementation with omega-3 fatty acids, such as those found naturally in fish oil such as docosahexaenoic acid and eicosapentaenoic acid. Several reviewers have pointed out various mechanisms via which omega-3 fatty acids can fight inflammation.20,21 For example, they can be released from cell membranes instead of arachidonic acid (AA) and compete with AA for subsequent oxidation via the COX, lipoxygenase (LOX), and P450 monooxygenase pathways. These fatty acids may also, at least partially, inhibit these pathways directly. A broader approach than exclusive COX-2 inhibition makes sense because products of COX action are not the only concern in colon cancer. For example, one of the products made in the lipoxygenase pathway, 12(S)-HETE, may increase the ability of tumors to metastasize.22 An additional note regarding different types of fatty acids is worth mentioning—at least in chemically induced colon cancer, the incidence and volume of tumors in rats that are fed fish oil is significantly lower than in groups who are fed beef tallow, soybean oil, or alkana oil.23 And, while a diet high in cereal fiber and containing enough omega-3 fatty acids is certainly important, there are also other factors to consider. A recent review of European studies suggests the importance of maintaining a reasonable body weight and including regular exercise in order to decrease colon cancer risk.24
There is also evidence that draws attention to the importance of healthy gut microflora. For instance, ingestion of fermentable probiotics, such as oligofructose and inulin, has been shown to lead to an increase in the growth of friendly bacteria, such as bifidobacteria.25,26 An increase in friendly bacteria has been reported to decrease colonic mucosal cell proliferation and to
Table 10-1. Preventing Colon Cancer: What to Tell Your Patients
Suggested for Prevention
Tell your Patients
Increase intake of total fiber cereals Increase omega-3 fatty acids
Support healthy gut flora
Vitamin E (g- or mixed- tocopherol) Curcumin
Selenium Calcium Vitamin D
Include cold water fish in the diet (such as salmon) weekly; also, include flaxmeal or cold-pressed flaxseed (Linum usitatissimum) oil, 2,000 mg 3 times per day.
Eat a variety of fresh fruits and vegetables that contain the oligosaccharides that are necessary for the growth of friendly bacteria; consider a quality probiotic supplement containing bifidobacteria and lactobacillus.
Take a quality multivitamin that provides at least 400 mg per day.
Take 400-1,200 IU per day.
440 to 2,200 mg curcuma extract, containing curcumin 36 to 180 mg per day.
Take 200 mg per day.
Take 1,200 mg per day.
decrease tumor biomarkers, such as tumor ornithine decarboxylase and ras-p21.25 One of the products made by bifidobacteria, butyrate, may be of special interest in colon cancer. In fact, in a model that included rats with induced colitis (itself a risk factor for colon cancer) or with colitis plus induced colon cancer, rats that received butyrate enemas showed a significantly lower incidence and size of induced tumors. An added finding was that the rats with colitis showed a normalization of glutamine metabolism,27 the most abundant amino acid in intestinal tissue.
In addition to telling your patients to consume generous amounts of cereal fiber and foods that are rich in omega-3 fatty acids, while maintaining healthy gut microflora, there are several other key nutrients that may be considered in an effort to maintain a healthy and cancer free-colon. (See Table 10-1 above.)
One nutrient that is especially important for colon health is folic acid. In 1998, the results of a significant prospective study of more than 88,000 nurses suggested that intake of greater than 400 mg per day at the beginning of the study was associated with a significant decrease in colon cancer risk, even after controlling for other factors such as intake of vitamins A, C, D, and E, and calcium. In addition, women who consumed multivitamins that contained folic acid, for 15 years throughout the study, had a dramatic decrease in colon cancer risk compared to women who did not consume such vitamins.28 In fact, the relative risk (RR) was 0.25 for women ages 55-69 who used a multivitamin that contained folic acid. This dramatic decrease in risk after a number of years may be not only be an important indication of the benefits of folic acid but also of the synergistic benefit of taking the needed vitamins and minerals supplied in multivitamins consistently over a significant portion of the lifetime. Also, it is useful to remember that it can take years before a study is able to detect a statistically significant difference between groups that are and are not getting supplements.
Curcumin's ability to block initial DNA damage and to limit progression make curcumin a very promising preventive agent.
Another prospective trial highlights the importance of assuring adequate folate intake, especially when methionine levels are low and alcohol consumption is heavy.29 In this study of almost 48,000 men, those who drank more than two drinks a day had a substantially increased risk (roughly double) of developing colon cancer compared to those who drank less than or equal to a quarter of a drink per day. In men who drank more than two drinks per day and had a low-folate, low-methionine diet, their risk roughly tripled for occurrence of any kind of colon cancer and was higher still for cancer of the distal colon. While there may be several mechanisms via which folic acid helps to prevent colon cancer, recent research suggests that one important role may be maintaining the genetic integrity of the DNA coding for the important tumor-suppressor gene, p53.30 Interestingly, however, in a recent double-blind, placebo-controlled, randomized clinical trial with 1,021 men and women with a recent history of colorectal adenomas, patients were given 1 mg per day of folic acid or placebo and=or aspirin. Folic acid supplementation was associated with higher risks of having three or more adenomas and of noncolorectal cancers and the incidence of at least one advanced lesion was 11.6% for the folic acid group compared to 6.9% in the placebo group.31
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