Results from a large-scale, placebo controlled clinical trial known as CAPP2 (Colorectal Adenoma/Carcinoma Prevention Programme 2) showed a 60% reduction in non-colorectal cancer among adults with Lynch Syndrome (hereditary nonpolyposis colon cancer) taking resistant starch (RS), a prebiotic dietary fiber.

This effect was particularly pronounced for upper gastrointestinal cancers including esophageal, gastric, biliary tract, pancreatic, and duodenum cancers. The benefit lasted for 10 years after consumption of the supplement.

The study was published in Cancer Prevention Research in July of 2022.¹

Study Design and Details

The clinical trial included 463 adults who received 30 grams/day of a supplement containing approximately 13 grams of RS2 and RS3 resistant starch and 455 participants who received a highly digestible corn starch placebo.

The average duration of consumption was 29 months and the mean age of participants was 45 years old at the beginning of the study.

Interventions took place between 1999 and 2007. At the completion of the study, there was not a significant difference in colorectal cancer, but the trial did find a significant reduction in colorectal cancer from aspirin.^2-3 Aspirin is now a recommended protocol to reduce the risk of colorectal cancers in individuals with Lynch Syndrome.

This July, a follow-up analysis was published which examined the total cancer onset in this population. In the 10-year follow-up period, there were just 5 new cases of upper GI cancers (which included stomach, duodenal, bile duct, and pancreatic cancers) among the 463 participants who had taken RS, compared to 21 among the 455 people who were on the placebo.

There were extracolonic cancers among 27 participants in the RS group (and 29 cancers overall) compared with 48 participants in the placebo group (and 53 cancers overall). This is relevant because upper GI cancers are more difficult to diagnose and consequently kill more people than colorectal cancer.

In 2018, approximately 4.8 million new cases of gastrointestinal cancers and 3.4 million related deaths occurred worldwide. GI cancers account for 26% of the global cancer incidence and 35% of the cancer-related deaths.⁴

Stomach, esophagus and pancreatic cancer accounts for 5.7%, 3.2% and 2.5% of new cancers diagnosed, respectively, and 8.2%, 5.3%, and 4.5% of cancer deaths. In contrast, colorectal cancer accounts for 9.2% of the deaths out of the 10.2% of cancers diagnosed, as public health campaigns have increased the early detection and favorable outcomes.

Upper GI cancers are diagnosed much later, accounting for 11.4% of cancer incidence and 18% of cancer mortality.

Resistant Starch

Resistant starch is defined as starch and starch degradation products that resist digestion and enter the large intestine, where they are fermented by the resident bacteria as a prebiotic dietary fiber.

Before processed foods were common, people regularly consumed 35-50 grams of resistant starch per day. However, consumption of resistant starch today has fallen to only 4-6 grams/day.

According to Dr. John Mathers, one of the principal investigators at Newcastle University in the UK, “Resistant starch can be taken as a powder supplement and is found naturally in peas, beans, oats, and other starchy foods. The dose used in the trial is equivalent to eating a daily banana; before they become too ripe and soft, the starch in bananas resists breakdown and reaches the bowel where it can change the type of bacteria that live there.

“Resistant starch is a type of carbohydrate that isn’t digested in your small intestine,” he continued, “instead it ferments in your large intestine, feeding beneficial gut bacteria—it acts in effect, like dietary fiber in your digestive system. This type of starch has several health benefits and fewer calories than regular starch. We think that resistant starch may reduce cancer development by changing the bacterial metabolism of bile acids and to reduce those types of bile acids that can damage our DNA and eventually cause cancer. However, this needs further research.”

Previous Cancer Research

Researchers have been investigating resistant starch’s potential role in cancer prevention for decades.

Resistant starch is fermented by many colonic bacteria, and is notable for producing high levels of butyrate, a short-chain fatty acid. Butyrate has been shown to suppress cancer cell proliferation and may enhance programmed cell death, or apoptosis of cancer cells.

There is also evidence from short-term mechanism studies that RS and/or its fermentation end products is antineoplastic. One example is a well-controlled clinical trial in which RS reduced multiple biomarkers of cancer risk in healthy adults who consumed high intakes of red meat (a risk factor for bowel cancer) for 4 weeks.⁵

A clinical trial has also shown that RS reduced fecal concentrations of total and secondary bile acids.⁶ While the researchers try to identify the exact mechanism and pathways, the reduction of cancer incidence in such a large clinical trial is noteworthy and an important milestone.

Lynch Syndrome

Individuals with Lynch Syndrome have significantly increased risk of developing many types of cancer due to DNA mismatch-repair (MMR) gene defects. These abnormalities underlie Lynch Syndrome, an autosomal dominant genetic defect that confers a predisposition to many types of cancer, including colorectal, endometrium, ovary, stomach, small intestine, pancreas, bile duct, urinary tract, brain, and skin cancers.

In patients with Lynch Syndrome, cancers appear at a mean age of 42.5 years, and the first diagnosis of colorectal cancer occurs at a mean age of about 45. The risk of colon cancer among mutation carriers is 10% over a period of 10 years.

This population was chosen for this intervention because the increased incidence of cancers developing in this population makes it more likely that a potential benefit can be identified and quantified.

Resistant Starch and Diabetes

This study is not the first evidence of significant metabolic health benefits from the prebiotic fermentation of resistant starch.

Resistant starch has also been shown to increase insulin sensitivity in approximately 20 clinical trials using high amylose corn supplements and foods, green bananas, and raw potato starch. It improves insulin sensitivity within hours and appears to be the result of the fermentation metabolites causing changes in the expression of the genes that control peripheral insulin sensitivity.

In 2016, the U.S. Food and Drug Administration approved a qualified health claim stating that limited evidence suggests that resistant corn starch reduces the risk of type 2 diabetes.⁷

References

1. Mathers, J. et al. (2022). Cancer prevention with resistant starch in Lynch Syndrome patients in the CAPP2-randomized placebo controlled trial:  planned 10-year follow-up. Cancer Prevention Research 2022; 15(9):623-634. https://doi.org/10.1158/1940-6207.CAPR-22-0044

2. Mathers, J. et al. (2012). Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomized controlled trial, Lancet Oncology. 2012; 13(12):1242-9. https://doi.org/10.1016/S1470-2045(12)70475-8

3. Burn J., et al. (2008.) Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome, New England Journal of Medicine. 2008; 359(24):2567-78. https://doi.org/10.1056/NEJMoa0801297

4. Arnold, M. et al. (2020). Global Burden of 5 major types of gastrointestinal cancer. Gastroenterology. 2020: 159(1): 335-349.e15. https://doi.org/10.1053/j.gastro.2020.02.068

5. Le Leu, R. et al. (2015). Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomized clinical trial. British Journal of Nutrition 2015; 114:220-30. https://doi.org/10.1017/S0007114515001750

6. Grubben, M. et al. (2001). Effect of resistant starch on potential biomarkers for colonic cancer risk in patients with colonic adenomas. Dig Dis Sci. 2001; 46:750-6. https://doi.org/10.1023/a:1010787931002

7. https://www.regulations.gov/docket?D=FDA-2015-Q-2352