Skip to content

In some not-so-surprising news, a recent study found that participants who consumed sugar substitutes showed an altered microbiome and spikes in blood glucose.

Since the introduction of diet drinks in the 1950s, the decades-long controversy around the safety of sugar substitutes has continued. Theories surrounding sweeteners such as saccharin, sucralose, and stevia contend that they do “more” than satisfy a sweet tooth without sugar calories. But what that ‘more’ actually is hasn’t been easy to establish.

In previous studies, researchers found that these nonnutritive sweeteners don’t just travel through the body unnoticed. The new study, published in Cell, links two of the sweeteners—saccharin and sucralose—to spikes in glucose levels and suggests all four are connected to a shift in gut microbe profiles. Whether these findings translate into trouble or advantage remains to be seen.

“It’s cool science and was very well designed, thought out, and executed,” says Dylan Mackay, an assistant professor of nutrition and chronic disease at the University of Manitoba, who was not involved in the study. “I’ve always wanted to do these more at-home trials, and they were able to pull it off in a really interesting way.”

In 2014 researchers found a link between microbiome changes and blood glucose responses in mice after intake of sugar substitutes. For the new study, scientists selected participants from more than 1,375 people, ruling out anyone who consumed noncaloric sweeteners in their regular daily life, to see if those same links applied to humans.  

Some had already unknowingly done so through protein powders, chewing gum, or low-sugar snacks or desserts.

The researchers split the final 120 participants into six groups of 20. 

In four of the groups, participants consumed commercial packets of one of the four sweeteners at levels below their federal daily limit. 

A fifth group consumed only the filler used in these packets, commonly added to increase the tiny amount of sugar substitute they contain. Finally, the sixth group had no intervention.

The participants consumed their assigned sweetener or the filler during the two weeks. In addition, they took oral glucose tolerance tests, which measure the body’s response to sugar and can be employed to diagnose some forms of diabetes. For these tests, they drank a glucose solution every morning after overnight fasting and used home-based continuous glucose monitors to track their blood glucose levels. Oral and stool samples were collected from the participants to analyze the species of microbes they hosted. Researchers also measured levels of some products of metabolism in the blood.

They found that the participants who consumed saccharin or sucralose had a steeper blood glucose response than any other group. Likewise, when participants consumed any of the four sugar substitutes, their gut bacteria profile changed during the two weeks of intake. Levels of the metabolic products changed too. For participants who took saccharin, a type of amino acid production increased, echoing patterns seen in people with diabetes.

To confirm a link between microbial profiles and blood glucose responses,

the investigators took specimens from the human participants with the highest and lowest spikes after sweetener consumption and orally administered them to germ-free mice. 

Study author Eran Elinav explained that the mice exposed to microbiomes from human “top responders” showed changes in their blood glucose, saying that “very significantly mirrored those of the donor individuals.” 

Eran Elinav is the principal investigator of the Host-Microbiome Interaction Research Group at the Weizmann Institute of Science in Rehovot, Israel, and director of the Microbiome and Cancer Division at the German National Cancer Center in Heidelberg.

Prof. Mackay said the findings in mice “are interesting mechanistic evidence that maybe [these sweeteners] are having an effect.”

And Elinav noted that the effects of the sweeteners on blood glucose are likely highly personalized. But the results suggest these compounds don’t just pass through the body, as some originally thought.

Mackay says that part of the personalized response will relate to the health of the person involved. For example, the findings “can’t extend to people who may be overweight or are obese or have impaired glucose tolerance or type 1 or type 2 diabetes,” he says.

The findings don’t settle the question of whether any effects will be meaningful for human health. Elinav says that’s a subject to tackle in other studies. Mackay says that the researchers also don’t know if these effects will persist beyond the two weeks of exposure in the current study.

Mackay notes that the study involved healthy people without overweight or obesity and who represent only a subset of the population that consumes food and drink with these sugar substitutes. “From a user perspective, as someone with type 1 diabetes, almost everything I use has aspartame,” he says. “I’m not going to stop that and switch back to regular glucose or sugar-containing products because of these results.”

While this may not be a “smoking gun,” it should lead us to reconsider the amounts and quantities of fake sweeteners we use in our daily life. There’s no such thing as a free lunch… or a consequence-free sweetener!