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Low-calorie sweeteners may not be as healthy as we thought

Artificial sweeteners, from mice to humans

For more than a decade, Eran Elinav has been interested in discovering the links between nutrition, gut microbes and the risk of developing common diseases such as obesity and diabetes, in hopes of developing a personalized microbiome-based medicine.

In 2014, Eran Elinav and his colleagues found that saccharin, sucralose, and aspartame raise blood glucose in mice to significantly higher levels than those recorded in sugar-fed mice.

When gut microbes collected from mice fed artificial sweeteners were administered to mice that had no gut bacteria of their own and had never been given artificial sweeteners, their blood glucose levels skyrocketed as if they were consuming artificial sweeteners.

Eran Elinav says that in mice, some of these non-nutritive sweeteners are detectable and affect gut microbes, which have an amazing ability to metabolize many of these compounds. Eran decided to test whether the same applied to humans: could the altered gut microbes disrupt glucose metabolism?

Eran Elinav’s team began by examining 1,375 volunteers to see if there was any consumption of zero-calorie sweeteners in their daily lives. The researchers identified 120 adults who had not been exposed before and gave them one of the four most commonly used sweeteners for two weeks – saccharin, sucralose, aspartame and stevia. The volunteers were then monitored for a third week. The scientists compared their blood glucose responses to those of volunteers who were not given artificial sweeteners.

Within 14 days after the volunteers were given any of the four artificial sweeteners tested, the scientists observed significant differences in their gut bacteria populations. “We identified very distinct changes in the composition and function of gut microbes and in the molecules they secrete into the blood,” says Eran Elinav. This suggests that gut microbes respond quickly to artificial sweeteners.

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To test how artificial sweeteners affect the body’s ability to control blood sugar spikes after consuming sugar with meals, the volunteers’ blood glucose levels were monitored after they consumed a glucose test drink. Normally, blood glucose levels should peak within 15 to 30 minutes and then return to normal after two to three hours. If glucose levels remain high, this signals that the body is not processing and storing excess glucose properly, a phenomenon known as glucose intolerance.

In the Israeli study, sucralose and saccharin caused the volunteers’ bodies to become glucose intolerant – something that, if sustained, can lead to weight gain and diabetes. Aspartame and stevia did not affect glucose tolerance at the ingested levels tested.

“The glycemic responses induced by saccharin and sucralose, possibly by the gut microbiome, may be more pronounced,” says Eran Elinav.

To confirm that the disturbance in microbial populations disturbed blood glucose levels, the scientists administered fecal microbes from the feces of human participants to germ-free mice. This study found that the microbes from volunteers with high blood sugar levels also suppressed glucose control in the mice.

“The gut microbes – and the molecules they secrete into our bloodstream – are greatly altered in consumers of the four types of non-nutritive sweeteners,” says Eran Elinav. “Each of the groups responded in a unique way.”

Although the study did not follow the volunteers long-term, this work is the first to show that the human microbiome responds to non-nutritive sweeteners in a highly individual way. This can disrupt sugar metabolism in some, if not all consumers, depending on their microbes and the sweeteners they consume. “The study is very comprehensive in terms of the microbiome,” says Michael Goran.

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“This study, however, more than offering answers, raises new questions,” says Dylan Mackay, a human nutrition expert at the University of Manitoba in Canada and a diabetic. As the volunteers were monitored for being free from previous exposure to non-nutritional sweeteners, it is unknown whether a similar glucose dysregulation would be seen in people who regularly consume these sweeteners, or whether there may be some degree of adaptation, says David Katz. It is also unclear whether the differences observed between individuals may be due to genetic, epigenetic or lifestyle factors.

Should we switch to sugar?

Some scientists believe that changes in the gut microbiome after short exposure to non-nutritional sweeteners are not enough to sound the alarm. “It’s reasonable to assume that the variety of non-nutritional sugars has some sort of physiological impact,” says Karl Nadolsky, an endocrinologist at the University of Michigan. “However, projecting this onto clinical outcomes and concerns is a very big leap.”

“We still don’t have any knowledge about the persistence of these results,” says Dylan Mackay. “Is this something that happens when we are first exposed to these non-nutritional sweeteners? And will it go on forever?”

The study authors themselves caution that it may be necessary to study long-term exposure to different artificial sweeteners to fully assess the potential health effects due to altered microbiomes. However, the scientists also emphasize that their results should not be interpreted as a plea to consume more sugar as an alternative to non-nutritional sweeteners.

“On the one hand, sugar consumption remains a very serious health risk and is proven to contribute to obesity, diabetes and other health implications, and our findings do not support or promote sugar consumption.” says Eran Elinav. “On the other hand, the sweetener impacts we’ve shown mean we should be cautious.”

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This study provides very compelling evidence on short-term adverse effects and on the mechanisms that can cause the same long-term adverse effects, says David Katz. “But this does not mean that non-nutritional sweeteners should be substituted for sugar, in other words, it reveals that alternative approaches to reducing sugar intake should be prioritized.”

“We need better solutions to satisfy our sweet tooth,” says Eran Elinav. “For me, personally, simply drinking water is best.”

This article was originally published in English on site nationalgeographic.com

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