Artificial sweeteners, also known as non-nutritive sweeteners, have been around for nearly 150 years. Saccharin, for example, has been used as a sugar substitute for over a century after its accidental discovery by a chemist at Johns Hopkins University in 1879.
These chemicals are generally thought to be inert, with no broad metabolic effects beyond simulating a sugar hit in our mouth while eating. But over recent years scientists have begun to suspect these artificial sweeteners could be impacting our health in a variety of ways, from increasing cancer risk to making a person more likely to gain weight.
A large body of study has emerged over the past 10 years specifically looking at the effects of artificial sweeteners on the gut microbiome, but crucially, the vast majority of this research has only been conducted in animals. So it's still incredibly unclear how these chemicals affect the human microbiome, and the few studies performed to date have delivered relatively discordant results.
This new study set out to fill a gap in the knowledge by recruiting 120 volunteers with no recent history of consuming any kind of artificial sweetener. Because artificial sweeteners are so pervasive in all kinds of food products, the researchers had to screen well over 1,000 subjects before finding their small cohort.
The group was randomly split into six groups: four artificial sweetener groups (testing either aspartame, saccharin, stevia, or sucralose) and two controls (one testing glucose and another with no intervention). For two weeks each participant supplemented their meals with sachets of their allocated sweetener. Stool samples were taken before, during, and after the intervention, and blood and glucose tolerance tests were also conducted.
“In subjects consuming the non-nutritive sweeteners, we could identify very distinct changes in the composition and function of gut microbes, and the molecules they secrete into peripheral blood,” explained senior author Eran Elinav. “This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners. When we looked at consumers of non-nutritive sweeteners as groups, we found that two of the non-nutritive sweeteners, saccharin and sucralose, significantly impacted glucose tolerance in healthy adults. Interestingly, changes in the microbes were highly correlated with the alterations noted in people’s glycemic responses.”
To investigate whether the microbiome changes were directly causing the alterations in glucose tolerance the researchers took microbiome samples from the human volunteers and transplanted them into mice with no gut bacteria. Elinav said the effects on the animals were striking, with the altered human microbiomes directly influencing the animals’ glycemic responses.
“In all of the non-nutritive sweetener groups, but in none of the controls, when we transferred into these sterile mice the microbiome of the top responder individuals collected at a time point in which they were consuming the respective non-nutritive sweeteners, the recipient mice developed glycemic alterations that very significantly mirrored those of the donor individuals,” Elinav said. “In contrast, the bottom responders’ microbiomes were mostly unable to elicit such glycemic responses.”
So what do these findings mean for the average person who occasionally consumes artificial sweeteners? Not much, according to digestive health researcher Francisco Guarner, from the Vall d’Hebron University Hospital in Barcelona.
Guarner, who didn’t work on the new study, said the cohort was too small to generalize any conclusions, and the results were incredibly broad, with some sweeteners having no effect on participants and other sweeteners having mild effects. Guarner also suggested the doses of sweeteners used in the research were much higher than most people would take in their day-to-day lives.
“This is a very important limitation: 180 mg of saccharin a day for two weeks is equivalent to taking 50 tablets or 18 sachets of saccharin every day,” Guarner added. “I do not know anyone who takes such quantities. In the case of sucralose, the intervention would involve taking 20 sucralose tablets every day. Nobody does that.”
Other researchers have been much less critical of the new findings, calling the study “rigorous” and “well-designed.” Sarah Berry, from King’s College London, said the new study was interesting in demonstrating the transient effects of certain artificial sweeteners on glucose responses in humans, but any long-term health impacts cannot be extrapolated from these findings.
“The higher blood glucose responses following two of the sweeteners (saccharin and sucralose) but not all (aspartame and stevia), could inform the food industry as well as consumers of healthier low-sugar options,” said Berry. “However, more long-term studies would need to be conducted before re-formulation and consumer advice could be confidently delivered.”
Elinav is acutely aware the new findings are not nearly a conclusive answer to what kind of effects artificial sweeteners have on a human microbiome. What is immediately clear from this study is that these food additives are far from the inert chemicals previously thought, and their influence can dramatically vary from person to person. Elinav also stressed the answer is not a return to consuming high levels of natural sugar, as we have clear insights into the metabolic harms of high sugar consumption.
“In the meantime, we need to continue searching for solutions to our sweet tooth craving, while avoiding sugar, which is clearly most harmful to our metabolic health,” added Elinav. “In my personal view, drinking only water seems to be the best solution.”
The new study was published in the journal Cell Press.
Source: Cell Press
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