colon cancer: data for foods & supplements

Study 1

An animal study was conducted comparing how different fiber types protected intestinal cells from developing colon cancer. (50) Mice were fed either (1) a low fiber diet, (2) low fiber supplemented with soluble fiber (konjac glucomannan; inulin), or (3) insoluble fiber (cellulose). Mice were treated with azoxymethane, which is a chemical with potency in causing DNA damage in intestinal cells, causing colon cancer.   

Results from the study demonstrated that glucomannan and inulin soluble fibers exerted greater protective (anti-genotoxic) effects compared to cellulose (insoluble fiber). Lab correlative studies also showed increased expression of antioxidant enzymes. Furthermore, the proliferative index and expression of Cyclin D1 were lower in all fiber groups, indicting more stable cells (and less likely to transform into cancer cells).   

This study gives experimental (mice) evidence supporting that soluble fibers are more effective than insoluble fibers in protecting intestinal cells from DNA damage that may promote colon cancer. The associated lab studies also provide a good basis for biologic benefit of the fiber. Given the lack of serious side effects of fiber products, it is reasonable to consider use of soluble fibers preferentially.   

Study 2

A lab study was conducted in 3 colorectal cancer cell lines, studying the effect of the combination of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber. (53) The aim was to assess the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells (and therefore this protein helps cancer cells escape cell death).  

Analysis showed that treatment induced apoptosis and cell cycle arrest in all 3 cell lines. Furthermore, the mechanism was consistent, in that all 3 cell lines showed a decrease in proteins including surviving.  

Although done in cell lines only, this analysis revealed a pro-apoptotic effect that was consistently observed, and with the same mechanism, in all 3 cell lines. Thus it is possible that the combination of green tea and soluble fiber can promote apoptosis and cell death. However, the exact amount and frequency to take these in humans is not known.    

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Vitamin D

It has been observed that Vitamin D levels may inversely relate to colon cancer risk. It is also known that immune cells in the tumor microenvironment can convert 25-hydroxyvitamin D to bioactive 1α,25-dihydroxyvitamin D3. Therefore it was hypothesized that patients with a higher degree of lymphocytic reaction in intestinal cells may derive greater benefit from Vitamin D. To this end, a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study was conducted. (21)  

For patients with a more intense immune reaction (as measured in this study), a high 25-hydroxyvitamin D level was associated with a lower risk of colorectal tumors (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35). Furthermore, this benefit was not seen with lower level immune reactions.   

This is a valuable study as it provides biological rationale for why some patients obtain benefit from higher Vitamin D levels. This is also data from an American population of patients. Although a given individual will not know the degree of immune reaction in his or her own intestine, Vitamin D supplementation is a reasonable option for chemoprevention. As with all Vitamin D supplementation, levels and dosing should be monitored by a physician to avoid Vitamin D toxicity or other side effects. 

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Seaweed

Seaweed and its extracts are commonly consumed as food in eastern Asian countries. Countries such as Japan, where there is a high consumption of seaweed, interestingly has a low incidence of colon cancer. (31) To assess potential health benefits in colon cancer, mice exposed to azoxymethane (a genotoxic compound which induces colorectal cancer in mice) were fed one of three diets, in a study from South Korea (28). These included a diet containing 10% water-soluble, or 10% water-insoluble fraction of seamustard or seatangle, and a control diet.  

Evaluation of DNA methylation (which would otherwise be caused by azoxymethane and promoting colon cancer), water-soluble fractions of these seaweeds suppressed the level of methylation at O(6)-guanine. In other words, one of the mechanisms directly leading to colon cancer formation were suppressed by the addition of water soluble fraction of seaweed in the diet.  

Therefore there is direct laboratory evidence for the mechanism by which seaweed may suppress colon cancer formation. This study supports the use of a 10% water soluble fraction in a diet or supplement.  

The term “seaweed”, more generically, refers to multiple species of algae. Many compounds in both crude and purified forms have been tested to detect evidence of anticancer or cancer preventive activity, mainly in cell line experiments. The following summarizes some of the growing body of literature in published medical studies.  

Colon cancer cells were treated with laminarin from brown algae. Cell proliferation was inhibited via Fas and IGF-IR signaling through apoptosis pathways. Laminarin also decreased Bcl-2 family protein expression and inhibited cell cycle progression by regulating the ErbB signaling pathway. (31)  

Polysaccharides from algae are amongst the most frequent compounds studied. Fucoidan, a sulfated polysaccharide often found in brown algae, was tested in colon cancer cell lines. Experiments demonstrated that fucoidan suppressed growth, decreased metastasis and inhibited angiogenesis. Furthermore, apoptosis (cell death) was induced in colon cancer HT-29 and HCT116 cells in a dose-dependent and time-dependent manner. (33)  

Dactylone is a chemical compound whose structure is closely related to that of sesquiterpenoids, which are found in red algae (Laurencia species). In studies of cancer cell lines, multiple effects were reported, including the induction of G1-S cell cycle arrest and apoptosis. (35) In addition, decreased Rb protein phosphorylation was seen, and dactylone inhibited the expression of cyclin D3 and cyclin-dependent kinase.  

Among green algae, ulva fasciata extract from Ulva fasciata Delile (sea lettuce), was studied in colon cancer cell lines (HCT116 cells). (38) With treatment of this extract, both antiapoptotic and antioxidant effects were observed. Ulva fasciata was able to inhibit the growth of HCT116 human colon cancer cells by 50% at a concentration of 200 μg/mL. Analysis also demonstrated that there was alteration of the Bcl-2 family of protein expression, promoting apoptosis.  

Marine algae gradually accumulate high levels of minerals in seawater. In a mouse study, mice were given a multi-mineral product obtained from marine algae. It was seen that colon polyp formation was reduced whether mice were fed a high or low-fat diet. (37) It is known that obesity and high-fat diet (as in Western diets) is associated with colon cancer risk.  

Put together, there is evidence for seaweed and algae promoting apoptosis, decreased colon polyp formation, and other cell growth pathways being affected (e.g., ErbB signaling pathway). This body of literature provides a biologic rationale for why populations that consume higher amounts of seaweed may see a lower colon cancer incidence.   

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Pomegranate peel extract

Three natural extracts - pomegranate peel extract, papaya peel extract and seaweed extract – were tested for cancer prevention effect in a rat colon. Azoxymethane (AOM) was administered to 80 rats to induce colon cancer formation. (51) Specifically, the AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of pomegranate peel extract, papaya peel extract or seaweed extract, in either the presence or absence of AOM injections. There was also a control group that was fed a basal diet.  

After 12 weeks, colon tissue was examined for aberrant crypt foci and other signs of genetic damange (presumed to be induced by azoxymethane). The study discovered that treatment of AOM along with one of the extracts significantly reduced the cancer-causing effects of azoxymethane, both in terms of reduction of the development of aberrant crypt foci (a precursor to colon cancer development) and by an antioxidant effect (glutathione depletion and lipid peroxidation observed).   

This well-conducted study with appropriate control groups lends evidence that the relatively simple intervention of nutritional extracts was able to reduce the rate of endpoints such as aberrant crypt foci. Along with an antioxidant effect observed, there may be a true chemoprevention effect of these extracts, which are readily available to incorporate into one’s diet. 

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Ginger

An Italian laboratory effort measured the relative potency of different types of ginger sources. In colon cancer cells, hydroalcoholic extract of ginger peel extract was more potent than ginger pulp hydroalcoholic extract. Ginger pulp hydroalcoholic extract showed higher anti-inflammatory and antioxidant activities. (18)  

This was a small study, perhaps chiefly demonstrating that all ginger sources are not equal. Turmeric is a type of ginger that has a larger body of literature. 

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