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January 20, 2021
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High saccharin intake ‘insufficient’ to alter glucose tolerance, gut microbiota in 2 weeks

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Short-term saccharin supplementation did not alter the gut microbiota or cause glucose intolerance in a cohort of healthy adults, according to study findings published in Microbiome.

“Short-term saccharin supplementation at the maximum allowable daily intake set by the FDA is insufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans,” George Kyriazis, PhD, assistant professor in the department of biological chemistry and pharmacology at Ohio State University College of Medicine, told Healio. “It should be noted that the saccharin intake in our study was practically magnitudes higher than the saccharin intake of an average U.S. consumer. We even supplemented the regular diet of healthy mice with a saccharin dose four times higher than the human dose for an extending duration, but mice remained metabolically healthy without significant changes in their gut microbiota.”

Kyriazis is an assistant professor in the department of biological chemistry and pharmacology at Ohio State University College of Medicine.

Kyriazis and colleagues conducted a double-blind, placebo-controlled study to analyze the effects of saccharin on gut microbiota and glucose tolerance. Forty-six participants were randomly assigned to a 2-week supplement of saccharin containing the maximum acceptable daily intake (n = 13), lactisole, a sweet taste inhibitor (n = 12), saccharin with lactisole (n = 10) or placebo (n = 11). Participants were healthy adults aged 18 to 45 years who consumed less than a can of a diet beverage or a spoonful of noncaloric artificial sweeteners weekly for at least a month, had a BMI of less than 25 kg/m2 and were weight stable in the 3 months before enrollment. A stool sample, blood sampling and an oral glucose tolerance test were conducted at a baseline visit in which participants were provided with a 2-week supply of treatment capsules. The same samples and tests were conducted again after the 2-week supplement was finished. All treatment groups received a 2-week pulp filler/placebo capsule after the 2-week supplement was completed. More data were gathered at the end of the washout period.

The findings showed no change in glucose responses after 2 weeks of saccharin supplementation. There was no difference in glucose excursions among the four groups during the washout period. An analysis of rRNA gene sequencing of fecal samples showed participants in all groups had similar gut microbial diversity. There was also no difference in taxonomic diversity and evenness between the cohorts. Analysis of microbial activity showed no effects from the saccharin supplementation.

Researchers confirmed the findings in a parallel 10-week study in which a high dose of pure saccharin was put into the drinking water of a group of T1R2-deficient mice that do not have functional sweet taste receptors and cannot taste saccharin, and a group of wild-type littermate controls. Mice were randomly assigned to drinking water with saccharin or water only for an additional 10 weeks. The saccharin dose was equal to four times the maximum allowable daily intake for humans.

In the parallel study, there were no changes in glucose tolerance in the T1R2-deficient or wild-type mice that took saccharin, and no differences were found in microbial diversity or taxonomic diversity and evenness. There was an age-dependent increase in short-chain fatty acids in wild-type mice taking saccharin, but the same effects were not seen in T1R2-deficient mice, suggesting a potential role of intestinal sweet taste receptor in gut metabolism.

“The clinical significance of our null findings should not be underestimated since it emphasizes that the recommended saccharin use is likely safe for healthy consumers that wish to substitute dietary sugars for weight management or caloric control,” Kyriazis said. “However, it is still unclear whether this recommendation is applicable to all populations and whether our results can be extrapolated to all other noncaloric artificial sweeteners.”

Kyriazis said the absence of a negative saccharin effect in the findings does not necessarily contradict previous research showing some harmful effects of noncaloric artificial sweeteners.

“High noncaloric artificial sweetener consumption may exert negative health outcomes accommodated by other physiological or dietary parameters,” Kyriazis said. “Future interventional studies should study other noncaloric artificial sweeteners and focus in identifying the pathophysiological or lifestyle parameters that may make noncaloric artificial sweeteners consumption harmful.”

For more information:

George Kyriazis, PhD, can be reached at georgios.kyriazis@osumc.edu.