Are Artificial Sweeteners Really

Harmless?
Megan Brooks
August 19, 2022
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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 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."
Experts Weigh In

Several experts weighed in on the results in a statement from the UK nonprofit 

organization, Science Media Centre.
Kim Barrett, PhD, distinguished professor of physiology and membrane biology,
University of California, Davis, School of Medicine, said: 'The present study is a
large step forward to understanding the impact of NNS in humans, with a very
rigorous design and follow-up work in mice to assess underlying mechanisms
and causality. Importantly, the work is a major advance because the authors
were careful to exclude participants who knowingly or unknowingly ingest NNS in
their normal diet. They found that, while there was variability between subjects,
two NNS, saccharin and sucralose, provoked intolerance to a glucose load (a
marker of metabolic dysfunction) and also caused specific changes in the gut
microbiome and the chemicals these microorganisms produce.

"Furthermore, by implanting the fecal microbiome from those

subjects who showed greater or minimal glucose intolerance
responses into germ-free mice, they could reproduce the
respective glucose intolerance in the mice, implicating the effect
of the NNS on the microbiome as the cause of the metabolic
dysfunction. Caveats about the study include the fact that only
young, healthy subjects were included, and the NNS were only
given for two weeks. Nevertheless, this well-designed study
indicates the potential for NNS to have adverse effects in at least
some individuals, and should prompt additional work as well as,
perhaps, providing an explanation that diet drink consumption is
often associated with greater rather than reduced levels
of obesity," she adds.
"Ultimately, perhaps we should not be surprised by the findings,
since NNS are recognized by human taste receptors even
though they are noncaloric, and bacteria are also well known to
have the capacity to sense chemicals in their environment and to
change their behavior accordingly."
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.
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.
Ascensión Marcos, PhD, research professor and director of the
Immunonutrition Group at the Institute of Food Science and
Technology and Nutrition of the Spanish National Research
Council, noted: "This is a good study. However, as usual, one
can always see 'drawbacks.' Of the 19 sweeteners approved in
the EU, only four appear in this article, so no results can be
extrapolated. As we also found in a recently published review,
the authors go so far as to observe an effect on the gut
microbiota with altered glycemic response for saccharin and
sucralose.
"In any case, although the N (the number of participants in the
study) is fine (120), there are only 20 in each arm of the
study...and the intervention time is short, only 2 weeks. In terms
of nutritional status, there are several groups, and obesity is not
taken into account, only overweight.
"In principle, it would be preferable to differentiate by case, by
nutritional situation, by pathology, even by geographical area,
since in Latin America the population has been consuming
different types of sweeteners for years and could possibly have
adapted their microbiota.
"I think that, in general, taking these points into account, it may
be difficult to draw conclusions."
Kathy Redfern, PhD, lecturer in human nutrition, University of
Plymouth, United Kingdom, said 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. McConway and Redfern report no relevant financial
relationships.
Cell. Published online August 19, 2022. Full text