First off, the authors look at the effects of three
common non-caloric artificial sweeteners (NACs) on glucose tolerance in mice.
Glucose tolerance is a test that measures clearance of glucose from the
bloodstream, usually two hours after ingesting glucose. Elevated levels are an
indicator for insulin resistance and pre-diabetes. Sucralose (in Splenda®),
aspartame (in Equal®), and saccharin (in Sweet’N Low) all led to higher glucose
levels in mice, although by the final two hour time-point, the difference to
the control group became less significant. For the rest of the studies, they
focus on saccharin and show that there is still a significant effect on glucose
levels when lower doses, corresponding to the FDA’s maximum acceptable daily
intake (ADI) dose are given for five weeks.
In recent years, the importance of commensal bacteria
living in the gut (the gut microbiota) in immunity and
metabolism has become appreciated. Therefore the scientists wanted to determine
if gut microflora had an impact on the mice's response to saccharin. Remarkably, saccharin
ingestion no longer led to glucose intolerance when broad-spectrum antibiotics
were given to mice concurrently with saccharin for four weeks. The author’s
measured the composition of the types of bacteria present in the stool of the
mice fed both diets and discovered that the composition of the microbiome was
distinctly different from the control mice and that it had changed considerably
from before the mice were given saccharin.
To determine a causal relationship, the scientists
took bacteria-containing stool from saccharin-fed mice and transplanted them to
the control mice, which then exhibited glucose intolerance when measured six
days later. Stool from control mice cultured in vitro (in culture, outside the body) and then transplanted to
non-sweetener-fed mice also had glucose tolerance impairment, providing strong evidence
that saccharin changes the type of bacteria present in the gut, which in turn
negatively effects the metabolism in mice.
But what about humans? Here they look at 381
non-diabetic people and using questionnaires about food intake, including
sweetener use, they find a positive correlation between long-term sweetener use
and several parameters of metabolic impairment, including glucose intolerance
tests. In the final, and perhaps most startling part of the study, seven individuals
with no history of sweetener use were given the FDA ADI dose of saccharin for
six days, glucose tolerance was measured, and stool samples were taken for
analysis of the gut microflora. Four out of the seven showed impaired glucose
tolerance. Interestingly these “responders'” microbiome was very different
from the “non-responders'” (those whose glucose levels did not change
significantly after being given saccharin) and the microbiome of the responders
changed after treatment while the non-responders did not. Finally, stool from
responders was able to induce glucose intolerance when transplanted to mice
while non-responders’ did not.
These final results are very intriguing but the sample
size is so small as to make it hard to make definitive conclusions. In case you
are curious as to whether the doses given (360 mg) were comparable to what an
average user may ingest, 360 mg of saccharin would be the equivalent of 10
packets of SweetN’ Low® (so maybe 5 cups of coffee with 2 packets each). Most
sodas stopped using saccharin awhile ago, but Tab soda, where available, contains
64 mg of saccharin, so 5 to 6-12 oz. cans of Tab everyday are needed to reach
the levels in the study.
Still, the study is important and deserves its publication in the prestigious journal, Nature. It is not the first study to discover a change in microflora with sweeteners. It appears, that Splenda® leads to changes in gut microbiota in mice as well (Mohamed et al., 2008) and led to increased glucose levels in the blood and humans (Pepino et al., 2013), although only seventeen people were tested in the latter study. Of course, it makes me interested to know if I am a responder or not and if we can eventually take stool samples and predict whether a persons’ microbiome will be negatively affected by sweeteners? While I would not advocate for others to change their sweetening habits based on this study, I would strongly suggest for similar studies with larger population sizes and perhaps lower, more normal doses, over longer periods of time.
Still, the study is important and deserves its publication in the prestigious journal, Nature. It is not the first study to discover a change in microflora with sweeteners. It appears, that Splenda® leads to changes in gut microbiota in mice as well (Mohamed et al., 2008) and led to increased glucose levels in the blood and humans (Pepino et al., 2013), although only seventeen people were tested in the latter study. Of course, it makes me interested to know if I am a responder or not and if we can eventually take stool samples and predict whether a persons’ microbiome will be negatively affected by sweeteners? While I would not advocate for others to change their sweetening habits based on this study, I would strongly suggest for similar studies with larger population sizes and perhaps lower, more normal doses, over longer periods of time.
References:
Mohamed B., et al. (2008). Splenda Alters Gut Microflora and Increases Intestinal P-Glycoprotein and
Cytochrome P-450 in Male Rats. J. Tox & Env Health, 71. doi: 10.1080/15287390802328630.
Pepino M. Y., et al. (2013).
Sucraolse affects glycemic and hormonal response to an oral glucose load.
Diabetes Care. doi: 10.2337/dc12-2221.
Suez, J., et al. (2014). Artificial
sweeteners induce glucose intolerance by altering the gut microbiota. Nature. doi:10.1038/nature13793