The Diet-Cancer Connection
By: Nita Jain
Tags: Science, Education, Cancer, Health, Food

Can consumption of resistant starch prevent colorectal cancer?

Colon cancer is the third most common type of cancer in the Western world and remains the third leading cause of cancer death in the United States. Particularly concerning is the recent rise of colon cancer among young adults. In 1973, Alan Berg observed that immigrants experienced an increased risk of colon cancer after moving to developed countries and converting to a Western diet.

Native South Africans have some of the lowest colorectal cancer rates and often consume a diet rich in fermented, whole grain-maize porridge, which is oftentimes allowed to sit outside for several days after being made. These types of foods tend to be very high in a type of fiber known as resistant starch, which certain types of gut bacteria such as Faecalibacterium and Roseburia can ferment to produce butyrate, a short-chain fatty acid that promotes apoptosis and exerts a wide range of other anti-inflammatory effects.

Butyrate serves as the primary energy source for the colonic epithelium, lowers luminal pH, and helps prevent the development of tumorigenic colonic cell populations. Indeed, studies show that the gut microbiota of colorectal cancer patients are characterized by significantly lower numbers butyrate-producing bacteria compared to healthy controls. Butyrate is a potent inhibitor of a class of enzymes known as histone deacetylases (HDACs), which relax chromatin structure and thereby enable the expression of genes that facilitate cell death and apoptosis. Murine models have shown that butyrate produced in response to resistant starch intake can inhibit colorectal carcinogenesis by enhancing the acute apoptotic response to genotoxic carcinogens. As Richard Le Leu of Flinders University of South Australia summarizes,

“Changes in amount of [dietary] fermentable substrate are capable of changing the biological response to DNA damage.”

Food exchange studies between Native Africans and African Americans have shown rapid reciprocal changes in the levels of bacteria responsible for sulfide production and those responsible for butyrate production. At baseline, the gut microbiota of Native Africans were characterized by higher numbers of starch degraders and butyrate producers while African Americans harbored higher numbers of potentially pathogenic Proteobacteria.

When African Americans switched to a Native African diet high in resistant starch and low in fat, butyrogenesis increased and colonic inflammation fell below the Native African baseline. The intervention diet consisted of hi-maize products, okra, lentils, rice, navy bean soup, mango slices, guava juice, samp, and other high-fiber foods. Conversely, Native Africans exhibited increased mucosal epithelial proliferation rates and colonic inflammation above the African American baseline upon switching to a Western diet of sausage links, hamburgers, French fries, meatloaf, Salisbury steak, noodles, corned beef hash, mashed potatoes & gravy, fried liver & onions, baked beans, and biscuits.

Not all fiber is created equal.

Photo by ja ma on Unsplash

In contrast to other types of fiber such as non-starch polysaccharides (NSP), resistant starch may confer unique benefits. Resistant starch (RS) refers to starch that is not absorbed in the small intestine and reaches the colon undigested where it may be fermented by gut microbiota to produce short-chain fatty acids such as butyrate. RS may be characterized into five types, the first three of which occur in a normal human diet:

· RS1 describes starch that is physically trapped within plant cell walls and protein matrices and includes whole grains, seeds, and legumes

· RS2 consists of native, granular starch and includes green bananas, raw potatoes, and high amylose corn starch

· RS3 comprises retrograded starches that are formed when starchy foods (e.g. rice, potatoes, pasta, bread, cornflakes) are cooked and cooled

· RS4 is composed of chemically modified starches used in the food industry to commercially produce baked goods

· RS5 usually refers to amylose-lipid complexes, consisting of starch and fatty acids, that form during food processing, which may include the use of emulsifiers

Currently, daily intake recommendations for resistant starch have not been established, nor is RS content reported on food composition labels. The latter may be difficult to estimate given the various factors that can affect RS concentrations, such as ripening, natural variation, and cooking and storage methods. Clinical trials studying the influence of resistant starch intake on cancer risk must consider both the type of resistant starch used as well as the dose.

Approximately 20 grams of resistant starch intake per day may be necessary to confer digestive health benefits while intakes of 6 to 12 grams of resistant starch per meal have been observed to inhibit postprandial increases in blood glucose and blood insulin. Americans are estimated to consume about 4.9 grams of resistant starch per day, slightly below the range needed to observe beneficial effects at a single meal and considerably short of the daily intake associated with health benefits.

Lack of dietary RS3 may explain why colorectal cancer more commonly occurs in the distal colon rather than the proximal colon.

Most types of fiber consumed in a typical Western diet primarily ferment in the proximal portion of the colon. The proximal colon is connected to the small intestine by the cecum while the distal end of the colon is near the rectum. As previously mentioned, colorectal cancer is characterized by a reduction in butyrogenic bacteria in the gut. Among the different types of resistant starch, RS3 may be of particular importance for butyrate production, especially when combined with RS2.

Flowchart created by author to illustrate how dietary resistant starch may drive changes in gut microbiota composition and luminal epithelial tissue to influence colorectal cancer risk.

RS2, such as raw potato starch, is granular, ferments quickly in the proximal part of the colon, and doesn’t change stool pH. On the other hand, RS3 is more crystalline, ferments slowly all the way to the distal end of the colon, and feeds SCFA-producing bacteria, thereby lowering colonic pH, preventing pathogen invasion, maintaining epithelial tissue health, and inhibiting carcinogenesis. A South African population consuming high levels of retrograded RS3 and low levels of dietary fiber was found to have significantly lower rates of colorectal cancer compared to another South African population that consumed higher levels of dietary fiber but lower levels of RS3; researchers speculated that RS3 fermentation was likely responsible for the observed protection.

A study examining the effects of resistant starch using human gut microbiota cultures found that RS3 doubled the proportion of Bifidobacteria in the distal colon and induced higher levels of butyrate production. The most common example of RS3 is cooked and cooled rice and potatoes, but green plantains, cassava, and taro also contain mixtures of several types of resistant starch, including RS3. A study examining the effects of resistant starch on several endpoints found that a high-RS diet produced a significant drop in fecal pH compared to a low-RS diet. The authors expound,