Food and Nutrition
Starch-Based ‘Super Food’ May Protect Against Variety of Diseases
Jun 21, 2017 - 12:41:28 PM

( - High-amylose maize starch is used to increase the fiber content in foods such as nutrition bars and improve the texture of gluten-free crackers and cookies, among other products.

And now, mouse studies suggest that modifying this starch by chemically linking acetate or butyrate to it might protect against autoimmune diseases such as type 1 diabetes and inflammatory bowel disease.

“I see this as the beginning of an era of the use of medicinal foods to treat human disease,” said Charles Mackay, PhD, senior author of a recently published study in Nature Immunology that found that the acetylate- and butyrate-enhanced starch benefited the immune system in the gut, protecting against type 1 diabetes in a strain of mice bred to develop the disease.

Mackay, a professor of immunology at Monash University in Melbourne, Australia, fed nonobese diabetic (NOD) mice modified high-amylose maize starch. The modified starch, when fermented by gut bacteria in the animals’ colons, produced higher levels of the short-chain fatty acids (SCFAs) acetate and butyrate than the nonmodified starch.

None of the mice fed a combination diet yielding high levels of both acetate and butyrate developed diabetes. The starches improved the integrity of the lining of the colon, reduced proinflammatory factors, and promoted immune tolerance. Type 1 diabetes in humans, like diabetes in the NOD mice, develops when T cells, a type of immune cells, mistake beta cells—the insulin-producing cells in the pancreas—as foreign invaders and attack and destroy them.

The findings suggest acetate and butyrate have different mechanisms of action. Acetate reduced the number of autoreactive T cells, key players in a variety of autoimmune diseases. Butyrate is the preferred energy source for the cells that line the colon, said Mackay’s coauthor Julie Clarke, PhD, team leader for “Nutraceuticals for Gut Health” at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) Health and Biosecurity in Adelaide, Australia. CSIRO is Australia’s national science agency.

“Shaping of the gut microbiota to one with substantial production of SCFAs might be a strategy for preventing or treating many human diseases,” Mackay, Clarke, and their coauthors concluded.

Will Humans Benefit?

If he can get funding, Mackay said, he would like to begin clinical trials within a year to test whether acetylated and butyrylated starch helps prevent development of type 1 diabetes in those at risk, namely relatives of people with the disease who have not been diagnosed with diabetes themselves but have an above-average risk of developing it. Those most at risk can be identified by screening for antibodies to the insulin-producing beta cells before symptoms appear.

But just because the acetate- and butyrate-enriched starch prevented diabetes in the NOD mice doesn’t necessarily mean it will work in humans, noted Julia Greenstein, PhD, vice president of discovery research at JDRF (formerly the Juvenile Diabetes Research Foundation), a US nonprofit that helped fund the Australians’ mouse study.

“The NOD mouse model is quite different than human type 1 diabetes,” she said. “Nearly every mouse of the NOD strain gets type 1 diabetes.” On the other hand, Greenstein said, only 50% to 60% of genetically predisposed humans develop type 1 diabetes, because environment also plays a role. “We don’t know what would happen if we gave it [the SCFA-enriched starch] to people,” although she added that the findings were nevertheless exciting. “It [acetate- and butyrate-enriched starch] has a big impact on these animals. No question.”

Jay Skyler, MD, deputy director for clinical research and academic programs at the University of Miami's Diabetes Research Institute, and formerly founding chair of Type 1 Diabetes TrialNet, an international consortium of scientists researching ways to prevent, delay, or reverse the disease, was less enthusiastic. “To me [the study] was ho-hum,” Skyler said of Mackay and Clarke’s recent article. “We’ve got [so many] things now that work in NOD mice, none of which worked in people [at risk of diabetes].”

One problem is that it’s not clear whether the difference in gut flora seen in patients with type 1 diabetes compared with those who don’t have type 1 diabetes is a cause or an effect of the disease, said Greenstein.

It’s also unclear whether the starch may prevent diabetes from ever occurring or simply delays it, and long-term preclinical and clinical studies are needed to address these possibilities, she added.

Beyond Type 1 Diabetes

Observational studies have linked high-fiber diets to a lower risk of colon cancer, while high quantities of red meat intake are associated with a higher risk of colon cancer.

In 2014, CSIRO scientists published a randomized trial that found that butyrylated high-amylose maize starch prevented an increase in colon cancer biomarkers in the rectal mucosa of people who ate a diet high in red meat.

“Our primary research for some years has been the effects of butyrate on reducing the risk of colon cancer,” Clarke said. “Butyrate has very important effects locally in the large bowel.” As the NOD mouse study suggests, butyrate affects the immune system in the gut and, possibly, systemically, she said.

Clarke is an investigator in an ongoing double-blind, randomized controlled trial of butyrylated high-amylose maize starch in 120 people with familial adenomatous polyposis (FAP). FAP is an inherited disorder characterized by the development of hundreds or thousands of colon polyps, beginning as early as puberty. Left untreated, virtually everyone with FAP will go on to develop colon cancer at a relatively young age.

The standard treatment for FAP is total colectomy, but that is not a cure. Precancerous polyps can still occur in the small intestine and the rectum, if it is left in place. So patients must take medication after colectomy, such as a nonsteroidal anti-inflammatory drug (NSAID) or even a chemotherapy agent to shrink new polyps. Both types of medication carry the risk of adverse effects, which is what makes the resistant starch an attractive option.

“Even a modest benefit would be well-received if it involved an agent that had little or no toxicity,” said Patrick Lynch, JD, MD, a professor in the department of gastroenterology, hepatology, and nutrition at MD Anderson Cancer Center, who has served as a consultant for the Australian FAP trial.

CSIRO scientists are also collaborating with Japanese researchers to see whether resistant starch enriched with butyrate protects against inflammatory bowel disease. Clarke and Koji Hase, PhD, a member of the pharmacy faculty at Tokyo’s Keio University, coauthored a study published in 2013 that showed feeding high-amylose maize starch with added butyrate protected against colitis in a mouse model by increasing regulatory T cells, which suppress inflammation and allergic responses in the mucosa of the colon. Hase is also analyzing the effect of butyrylated starch in a mouse model of rheumatoid arthritis, another autoimmune disease.

Is It a Food, Medicine, or Something in Between?

Research into the use of the enhanced maize starch as a way of preventing disease is moving slowly, due to regulatory and patent issues.

For example, although Mackay described the acetylated and butyrylated starch as a medicinal food, the US Food and Drug Administration (FDA) doesn’t recognize that term, agency spokeswoman Deborah Kotz said.

The starch isn’t a medical food either, according to the Orphan Drug Act, which defines such foods as “those formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition. … Medical foods are not those simply recommended by a physician as part of an overall diet to manage the symptoms or reduce the risk of a disease or condition.”

Although Mackay referred to the specially enhanced starch as a medicinal food, he said he considers it to be more like a dietary supplement. “You’ve actually got a foodstuff that is designed as a medicine,” he said. “It’s like a super, super food” that people can mix in beverages or sprinkle on their breakfast cereal or pasta.

“Unfortunately, with the amount required, capsules are not an option,” said Clarke, who describes the chemically modified starch as “sort of halfway between being a medicine and being a food.”

“It’s a research product,” she said. “We recommend to our (trial) participants that they mix it with something like chocolate milk.”

In 2016, the FDA agreed with a Yale School of Medicine expert panel that the acetylated high-amylose maize starch was “generally recognized as safe” for use as an ingredient in oral rehydration solutions for adults and children. That decision was based in part on research by Clarke, who coauthored a randomized trial presented at Digestive Disease Week 2013 that found that the addition of the acetylated starch to oral rehydration solution reduced the time to the first formed stool in patients with acute infectious diarrhea.

This past December, the FDA told Ingredion, a company based in Westchester, Illinois, that supplies high-amylose maize starch to the Australian researchers, that it could make qualified health claims on the packages of conventional foods, such as baked goods and pasta, containing the starch. Ingredion can claim that the starch might reduce the risk of type 2 diabetes, although it must add that the FDA “has concluded that there is limited scientific evidence for this claim.”

While some of the news coverage of Mackay’s article suggested that people could get a similar benefit from eating more fruits and vegetables, he called that notion “a bit simplistic.”

Natural foods don’t contain acetate and butyrate in amounts as large as those in the modified high-amylose maize starch, Mackay said. Nevertheless, the experimental benefits of the modified starch “speak to the fact that many of these diseases might have as their basis our poor diet.”

Clarke echoed Mackay. “With particular conditions, perhaps we can’t get enough of these [short-chain fatty] acids with a healthy diet.”

Still, the modified starch likely can’t replace all of the nutrients found in, say, the Mediterranean diet, with its good fats, lean proteins, and plenty of fruits and vegetables, Clarke said.

“We shouldn’t take our foot off the accelerator in terms of getting people to have a healthy diet and lifestyle,” she said. “But I think that these products [acetylated or butyrylated starch] can add to that in specific situations.”


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