Sugar Substitutes, Gut Bacteria, and Glucose Intolerance

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Sugar Substitutes, Gut Bacteria, and Glucose Intolerance

The consumption of artificial sweeteners results in glucose intolerance mediated by changes in the gut microbiota in both mice and humans, researchers report.

By Anna Azvolinsky | September 17, 2014

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WIKIMEDIA, STEVE SNODGRASSNon-caloric sweeteners can spur glucose intolerance in mice and some people, according to a study published today (September 17) in Nature. Researchers from the Weizmann Institute of Science in Israel and their colleagues have uncovered “the unexpected effect that artificial sweeteners drive changes in the [gut] microbiota, which promote glucose intolerance,” said University of Chicago pathologist Cathryn Nagler, who studies how the microbiota regulate allergic responses to food and penned an editorial accompanying the study.

Immunologist Eran Elinav and computational biologist Eran Segal, both of the Weizmann Institute, identified changes in the composition and function of the mouse gut microbiome after the animals consumed artificial sweeteners—changes similar to those previously linked to obesity and diabetes in humans, the authors noted.

A previous study showed that sucralose can alter the rat gut microbiome—specifically, by decreasing beneficial bacteria—but this latest work pinpoints a microbe-mediated mechanism by which artificial sweeteners might influence glucose metabolism, said Yanina Pepino, who studies how non-caloric sweeteners influence glucose metabolism at the Washington University in St. Louis School of Medicine.

Elinav and Segal’s team observed that mice given a 10 percent solution of one of three types of commonly consumed commercial artificial sweeteners—saccharin, sucralose, or aspartame—in place of regular drinking water had elevated blood-glucose levels after 11 weeks compared to mice given either a 10 percent glucose solution or water alone. The researchers used saccharin for subsequent experiments as this artificial sweetener showed the most pronounced effect on glucose levels in preliminary trials. Mice fed a high-fat diet plus the 10 percent saccharin solution showed the same effect on glucose metabolism as animals given an even higher saccharin dose—comparable to the US Food and Drug Administration’s (FDA’s) upper limit for safe human consumption.

Four weeks of treatment with gut bacteria-depleting antibiotics reversed the glucose intolerance in mice that continued to receive saccharin. This led the team to examine whether the microbiomes of the mice were somehow altering glucose metabolism. Transplantation of feces from non-antibiotic-treated mice that consumed saccharin- or glucose-containing water into germ-free mice within six days induced the same blood-sugar elevations in animals that were never themselves exposed to the sweeteners.

“This is the elegant and home run experiment that shows causality in mice,” said Nagler.

Using shotgun metagenomic sequencing on the fecal samples, the researchers showed that mice given saccharin or those that received a fecal transplant from saccharin-fed mice had a different microbiome composition compared to mice given sugar or no sweeteners.

The team also found similar glucose metabolism and gut microbiota changes in humans.

In a cohort of 381 non-diabetic volunteers who answered diet questionnaires, those who regularly consumed artificial sweeteners—particularly those who consumed the highest amounts—showed higher fasting glucose levels, poorer glucose tolerance, and different gut microbe profiles compared to those who did not consume such sweeteners. The difference between the two populations remained even after correcting for body mass index.

Further, the team exposed seven young, healthy volunteers who did not have a history of artificial sweetener consumption to one week of the FDA’s maximum acceptable daily saccharin intake, and continuously monitored their glucose levels. Four of the seven volunteers showed a poorer glycemic response at the end of the week compared to their baseline responses. Those who showed no metabolic response to the sweetener had no change in their gut microbiomes, while those who exhibited the worst glycemic responses at the end of the week showed a different gut microbiota profile after sweetener exposure. Fecal transplants from two artificial sweetener-responder volunteers into germ-free mice resulted in a similar gut microbe profile and glucose intolerance as did transplants from saccharin-consuming mice. But the same transplants from two non-responder volunteers had no such effect in germ-free mice.

“The extensive work done with the microbiome [in this study] continues to point to the potential importance of our dietary habits on this previously underappreciated variable in our metabolism,”Christopher Gardner, a professor of medicine at Stanford University who was not involved in the study wrote in an e-mail to The Scientist. Gardner was the former chair of the working group of the American Heart Association that generated a position statement on artificial sweeteners in 2012. He added that while the dose of artificial sweeteners used in this study is acceptable according to the FDA, this high dose—equivalent to 340 milligrams of saccharin (8.5 packets of Sweet N’ Low) per day—is an unlikely dose for the typical artificial sweetener user.

Although the human data provide some evidence that artificial sweeteners may have a detrimental effect on glucose metabolism in a subset of people, the authors cautioned that additional studies are needed to understand who is susceptible to the potential negative effects of artificial sweeteners and to further elucidate the mechanism by which gut microbes may drive metabolic changes.

“I am very excited about these results because they demonstrate the need for more research,” said Pepino. “There are many aspects of these sweeteners that we don’t understand. Artificial sweeteners may have no calories  but mounting evidence indicates that they do have metabolic consequences and may not be the solution for having a sweet taste without the calories.”

J. Suez et al., “Artificial sweeteners induce glucose intolerance by altering the gut microbiota,” Nature, doi:10.1038/nature13793, 2014.  

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sugar, microbiome, human research, gut microbiota, Glucose metabolism, blood glucose and artificial sweeteners

Could the ‘miracle fruit’ help in the fight against obesity?

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Could the ‘miracle fruit’ help in the fight against obesity?

JOSH RUBIN

Special to The Globe and Mail

Published Tuesday, Aug. 12 2014, 3:31 PM EDT

Last updated Tuesday, Aug. 12 2014, 4:14 PM EDT

There’s a berry native to Cameroon, Gabon and the lowlands of West Africa that has a curious effect. Pop the small, red and surprisingly bland berry into your mouth and it temporarily tricks your taste buds into thinking that sour tastes sweet. Colloquially known as the “miracle fruit,” it has long been trendy among foodies hosting “flavour-tripping parties” and as a gimmick at high-end restaurants. One prominent U.S. chef, however, is out to prove that the miracle fruit has utility far beyond that of a parlour trick.

Homaro Cantu, of Chicago’s Moto restaurant, is an eccentric chef, famous for such cerebral dishes as edible menus made of soy paper. And he wants to take the miracle berry mainstream. Cantu is at the vanguard of molecular gastronomy, but he grew up in poverty in Portland, Ore., and spent three years living on the streets. He knows first-hand what it’s like to lack access to hearty and nutritious food.

Cantu is growing miracle berries in indoor farms to use instead of sugar at his restaurant, and he’s forging relationships with major food corporations. “I have two young daughters and I worry about their future and health. I’m concerned about what they consume and what is hidden in their everyday foods,” he says.

The consequences of our collective sweet tooth have been debilitating. The most recent figures cited by the Canadian Obesity Network indicate that 25 per cent of adult Canadians are obese and more than half are overweight, placing a burden of nearly $6-billion on the health-care system each year. South of the border, where an estimated 45 per cent of the population is expected to be obese by 2030, the epidemic is even more profound. Although researchers have not proven conclusively that excess sugar intake causes obesity, the balance of medical research is coalescing around this conclusion.

In March, the World Health Organization issued a report encouraging people to consume less than 5 per cent of their total daily calories from sugars. And in July, federal Health Minister Rona Ambrose announced a recommendation that Canadians limit their sugar intake to 100 grams a day.

“People aren’t addicted to sugar – what we’re really addicted to is sweetness,” says Cantu. “Since we’re never going to give that up, miracle berries are a great solution for our cravings, minus the calories and chemicals.”

The chef first stumbled across the berry in 2005 when he was asked to create something for a woman whose chemotherapy had altered her sense of taste (a common side effect called dysgeusia, in which food takes on a metallic tone). Cantu spent weeks experimenting by chewing on tinfoil until he was able to develop a recipe, a combination of the berry and edible paper, which neutralized the metallic taste. Since then, he’s provided more than 1,000 chemo patients with the berry free of charge and has spent the past decade working to unlock its full potential.

In his quest to cook without sugar, Cantu had to recalibrate the ratios of his recipes to get his dishes to look and taste just right – since apart from sweetness, sugar helps lend food its colour, texture, body and aroma. Diners at Moto responded enthusiastically to his concoctions and Cantu is now focusing on his latest project, a miracle-berry-themed café called Berrista, slated to open this fall.

The miracle berry (or Synsepalum dulcificum) is one of the only naturally occurring taste-modifiers in the world. Unlike honey or sugar, which activate sweet taste receptors, when you eat the berry a protein called miraculin temporarily masks sour tastes. For the following 30 to 45 minutes, foods that are unpalatable on their own become as scrumptious as their sugary counterparts. Refrigerating or heating the berry, however, nullifies this effect; in order to bring miraculin readily into our diets scientists need to figure out a way to stabilize the protein.

Researchers in Japan have successfully modified tomato and lettuce plants to produce miraculin. PepsiCo, meanwhile, is working with San Diego-based biotech company Senomyx to create an additive that, like miraculin, tricks people’s taste buds into detecting more sweetness than is present.

For his part, Cantu believes that bioengineering is too costly to be competitive. He grows the berry through a network of nine indoor farms in the Chicago area. And as a way to demonstrate the fruit’s viability as a sugar substitute, he published The Miracle Berry Diet Cookbook last year, with recipes ranging from raspberry cheesecake to teriyaki chicken. All the recipes incorporate low-glycemic ingredients such as lemons, limes and sour cream and each one indicates the amount of calories saved per serving by using the berry. (The berries, commonly sold in tablet form, are easily found online.)

If all goes according to plan, the first Berrista should open next month in Chicago’s Old Irving Park neighbourhood, with a jelly doughnut as its signature treat.

“It won’t have any refined sugar in it, and in order to make the jam we’ll take cherries and cook them down with a little bit of balsamic vinegar and water. It’ll have 250 fewer calories than anything you can find elsewhere,” he says. If the first location is successful, Cantu hopes to take the concept across the United States.

Could miraculin be the solution to the obesity epidemic? Not everyone is convinced.

“If people are buying the miracle fruit thinking it will do the entire job, I think time has taught us that there is no singular tool and that they will absolutely also require a life overhaul,” says Dr. Yoni Freedhoff, a weight-management specialist and assistant professor of family medicine at the University of Ottawa.

“We’ve lost the skill of cooking, and calories are being hoisted on us every single place we turn. If the suggestion is that because we’re going to eat fewer desserts with this we’re going to be okay, then the imprint is that we’re struggling primarily due to excess dessert,” says Freedhoff. “I really don’t think that’s the case.”

Anyone looking to commercialize miraculin will have to overcome significant regulatory hurdles. In 1974, the U.S. Federal Drug Administration declared that miraculin was an additive, meaning that the berries cannot be sold as a sugar substitute without further testing. Health Canada takes a similar stance.

In the 1970s a U.S. company called Miralin was on the verge of introducing the miracle berry into food as a sugar replacement until the FDA’s controversial ruling effectively shut it down. Reversing that decision would require years of testing.

“Anyone wanting to go down that route would likely be successful, as there is nothing unhealthy about miraculin. They’d just need to have the financing and patience to see it through,” says author Adam Gollner, who chronicled the story of Miralin in his book The Fruit Hunters.

If the ban is one day lifted, miraculin might still remain unappealing to large corporations – the cost of constructing greenhouses en masse or converting existing farmland could prove to be prohibitively expensive.

“It’s a hard plant to grow and its productivity is relatively low, since only a quarter of all plants ever bear fruit. When you compare it to the cost of artificial sweeteners, investing money in miraculin doesn’t really make economic sense at the moment,” says Laura Jones, a global food-science analyst at consulting firm Mintel.

Although Cantu won’t discuss details, he says he has been in talks with at least one major food company and is convinced that with the right partnerships, the paradigm will eventually shift from sugar to miraculin.

“The miracle fruit is good for everything,” he says. “We’re updating what should have been updated years ago.”

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