Are Artificial Sweeteners Really Harmless?

Medscape Medical News - August 19, 2022

New research discounts the long-held notion that aspartame and other nonnutritive sweeteners (NNS) have no effect on the human body.

In a study, researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.

The study was published online August 19,20-22 in the journal Cell.

Gut Reaction? 

Several years ago, a team led by Eran Elinav, MD, PhD, an immunologist and microbiome researcher at the Weizmann Institute of Science, Rehovot, Israel, observed that NNS affect the microbiome of mice in ways that could affect glycemic responses.

They have now confirmed this observation in a randomized controlled trial with 120 healthy adults.

Before the study, all participants strictly avoided NNS. During the trial, some remained NNS-free, while others used saccharin, sucralose, aspartame, or stevia daily for 2 weeks in doses lower than the acceptable daily intake.

Each NNS "significantly and distinctly" altered stool and oral microbiome, and two of the sweeteners (saccharin and sucralose) significantly impaired glucose tolerance, the researchers report.

"Importantly, by performing extensive fecal transplantation of human microbiomes into germ-free mice, we demonstrate a causal and individualized link between NNS-altered microbiomes and glucose intolerance developing in non-NNS-consuming recipient mice," they say.

They note that the effects of these sweeteners will likely vary from person to person because of the unique composition of an individual's microbiome.

"We need to raise awareness of the fact that NNS are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies," Elinav said in a news release.

For now, Elinav says it's his personal view that "drinking only water seems to be the best solution.”

Weighing the Evidence 

Several experts weighed in on the results in a statement from the UK nonprofit organization, Science Media Centre.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, United Kingdom, notes that the study does not show a link between all NNS and higher blood glucose levels in the long term (only after a glucose tolerance test).

"It did suggest, though, that some individuals who do not normally consume sweeteners may not tolerate glucose as well after consuming six sachets of either saccharin or sucralose mixed with glucose per day," Mellor says.

Kim Barrett, PhD, distinguished professor of physiology and membrane biology, University of California, Davis, School of Medicine, concurs, saying, "this well-designed study indicates the potential for NNS to have adverse effects in at least some individuals."

The study also does not provide any information about how people who normally consume sweeteners or people with either type 1 or type 2 diabetes respond to NNS.

"Therefore, for some people, it is likely to be a better option and more sustainable approach to use sweeteners as a 'stepping stone,' allowing them to reduce the amount of added sugar in foods and drinks, to reduce their sugar intake, and still enjoy what they eat and drink, on the way to reducing both added sugar and sweeteners in their diet," Mellor suggests.

Kevin McConway, PhD, with the Open University, Milton Keynes, United Kingdom, says it's "important to understand that the research is not saying that these sweeteners are worse for us, in heath terms, than sugar.

"But exactly what the health consequences of all this, if any, might be is a subject for future research," McConway adds.

Kathy Redfern, PhD, lecturer in human nutrition, University of Plymouth, UK, agrees.

"We still have a lot to learn about the human microbiome, and although this study suggests two of the sweeteners tested in this study (sucralose and saccharin) significantly affected glucose tolerance, these deviations were small," she says.

The International Sweeteners Association also weighs in, saying, "No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes."

They add that "a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota."

Nevertheless, Redfern says the results "warrant further investigation to assess how small changes in glucose tolerance in response to NNS consumption may influence longer term glucose tolerance and risk for metabolic complications, such as type 2 diabetes."

The study had no specific funding. Elinav is a scientific founder of DayTwo and BiomX, a paid consultant to Hello Inside and Aposense, and a member of the scientific advisory board of Cell. Mellor has provided consultancy to the International Sweetener Agency and has worked on projects funded by the Food Standards Agency that investigated the health effects of aspartame. Barrett, McConway, and Redfern report no relevant financial relationships. 

Cell. Published online August 19, 2022. <https://www.cell.com/cell/fulltext/S0092-8674(22)00919-9>