It has long been speculated that resistant starch (RS) may help to prevent colorectal cancer (due to the supporting information described below). However, cancer clinical trials are exceedingly expensive, require a lot of time and are rarely done.

After more than 25 years of investigations, researchers at the University of Newcastle hit the jackpot – not the expected jackpot but a tremendously important jackpot nonetheless.

Professors Tim Bishop, Sir John Burn and John Mathers had completed two major cancer studies (CAPP1* and CAPP2**) which showed no effect of resistant starch on colorectal cancer. With CAPP2, however, they followed-up with the participants for many years.  After 10-20 years, the RS group had significantly fewer extracolonic cancers, notably a 60% reduced incidence of cancers in the upper gastrointestinal tract (i.e., stomach, duodenal, bile duct and pancreatic cancers). This is especially significant because these types of cancers are more difficult to detect and consequently, result in higher mortality. (Arnold et al., 2020) The Mathers study reported that for people with Lynch Syndrome diagnosed under 65 years of age, 5-year survival is 0%, 29%, 61% and 67% for pancreatic, bile duct & gall bladder, stomach and duodenal cancers, respectively. These are significantly lower than the 88% survival for colon cancer and 93% survival for endometrial cancers. (Mathers et al., 2022)

The CAPP2 study included 918 adults with Lynch Syndrome – 463 people consumed 30 grams of resistant starch ingredients/day (a combination of Ingredion’s Hi-maize® 330 and Hi-maize® 240 resistant starch) containing approximately 10-15 grams of resistant starch depending on which analytical method is utilized) and 455 received the placebo (a highly digestible starch).  At the conclusion of the study, resistant starch had no detectable effect on cancer development. (Mathers et al., 2012)  The follow-up after ten years had been planned into the clinical protocol. After the ten-year follow-up, there was still no benefit in reducing colorectal cancer in the RS arm of the study.

The Newcastle University press release called it “astonishing” that the effect was seen to last for 10 years after they stopped taking the supplement.  In other words, the participants did not continue to consume resistant starch over the intervening years – their participation had ceased after about 29 months (the mean consumption duration within the study).

Supporting information on RS and cancer –

Animal and clinical studies as well as epidemiological evaluations have suggested that resistant starch likely has anti-cancer benefits:

Clinicals –

1. An earlier Mathers clinical trial with 65 colorectal cancer patients showed that four weeks consumption of RS reduced cell proliferation in the upper part of colonic crypts and changed gene expression that was consistent with anti-cancer benefits. (Dronamraju et al., 2009)
2. Another clinical study correlated resistant-starch rich foods with reduced risk of breast cancer in 306 women with newly diagnosed breast cancer compared to 309 healthy women as matched controls. (Tajaddini et al., 2015)
3. A clinical study with 23 older adults reported that RS prevented the pro-cancerous biomarkers seen following consumption of a high red meat diet. (Humphreys et al., 2014)

Epidemiological and meta-analysis studies:

1. Dietary fiber consumption is inversely correlated with colorectal cancer. (Ma et al, 2018) Resistant starch is a prebiotic, fermentable dietary fiber. Different types of dietary fiber have different effects (bulking, viscous and fermentable are major mechanisms), making further progress on these broad characterization difficult.
2. Resistant starch consumption was associated with lower cancer and all-cause mortality in a 2022 analysis of the US National Health and Nutrition Examination Survey (NHANES) database. (Wan et al., 2022)

In vivo animal studies:

1. RS promotes differentiation of cancer cells, returning them to normal behavior. (Malcomson et al., 2015)
2. RS reduces cell proliferation. (Hu et al., 2016)
3. RS increases apoptosis (programmed cell death) of cancer cells. (Le Leu et al., 2002, Le Leu et al., 2009)
4. RS reduces incidence of intestinal cancers. (Le Leu et al., 2007)

Animal studies have suggested that resistant starch’s production of fermentation-related metabolites are the key mechanisms contributing to anti-cancer benefits.  For instance, the short-chain fatty acid butyrate has been shown to suppress colon cancer. (Niekamp and Kim 2023). There are many metabolites produced by resistant starch’s fermentation and many different pathways may be involved.  (You et al., 2023)  If this is true, these benefits would not be feasible with non-fermentable bulking or viscous fibers like cellulose or psyllium, which do not produce such fermentation-related metabolites.

In conclusion, RS may be the most exciting development in the prevention of cancer within the food or drug industries in recent years.  There is an abundance of scientific data suggesting likely mechanisms, confirmed by epidemiological analyses. The latest CAPP2 study provides definitive evidence that the intestinal fermentation of prebiotic resistant starch can contribute hugely important metabolic benefits.  Congratulations to the Bishop, Burn and Mathers team on a fabulous new (and old as the participants consumed the resistant starch years ago) study!

*CAPP = Concerted Action Polyposis Prevention.  CAPP1 included 227 young people with familial adenomatous polyposis (FAP), an inhered genetic mutation that strikes the youth and, untreated, results in nearly certain case of colorectal cancer and early death. (Burn et al., 2011)

** CAPP2 included 918 adults with Lynch Syndrome, another genetic mutation that significantly increases the risk of cancer, particularly in people in their forties or fifties. In this syndrome, mutations have occurred in genes involved in cell division and fixing DNA errors, known as mismatch repair (MMR) genes.  These individuals have increased genetic risk of colorectal cancers, as well as cancers of the stomach, small intestine, liver, gallbladder ducts, urinary tract, brain and skin.  Women with this disorder also have high risk of cancer of the ovaries and endometrial cancer.

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