Written by Joyce Smith, BS. This study finds that short-term saccharin consumption at maximum acceptable levels is not sufficient to alter gut microbiota or induce glucose intolerance in healthy humans and mice.
The past thirty years of scientific research have pointed to a positive association between higher levels of non-caloric artificial sweetener (NCAS) consumption and the prevalence of type two diabetes (T2DM) and metabolic syndrome. While life-styles and health characteristics of the study populations may have contributed to these outcomes, the results, none the less, alarmed both the general public and medical community 1. Recognizing the need to mitigate these concerns through the use of well-designed interventional studies, Serrano and colleagues designed the following trial to investigate whether consumption of saccharin, and other NCAS, would alter gut microbiota and disrupt glucose levels in healthy individuals.
In a double-blind, placebo-controlled cross-over study 2 the team randomly assigned 46 healthy adults, aged 18 to 45 years, into four groups: high-dose saccharin containing the maximum acceptable daily intake 3 (n = 13), lactulose, a sweet taste inhibitor (n = 12), saccharin with lactulose (n = 10) or placebo (n = 11). All participants had consumed less than a can of a diet beverage or a spoonful of noncaloric artificial sweeteners weekly in the prior month and maintained stable weight and a body mass index (BMI) of less than 25 kg/m2 for 3 months prior to enrollment. Baseline stool and blood samples were collected and oral glucose tolerance tests (OGTTs) were conducted at a baseline visit and repeated after two weeks of treatment intervention at which time all treatment groups received a pulp filler/placebo capsule for a 2-week washout.
After two weeks of supplementation, saccharin did not alter glucose response. There were no differences in glucose readings among the four groups during the washout period. An analysis of rRNA gene sequencing of fecal samples revealed that participants in all groups had similar gut microbial diversity and no difference in taxonomic diversity between the groups. Microbial activity analysis found no effects from the saccharin supplementation.
To confirm findings, a 10-week parallel study was done, in which high dose pure saccharin (at four times the maximun daily allowance for humans adjusted for mouse size) 4 was added to the drinking water of chow-fed T1R2- KO deficient mice and a group of wild-type (WT) littermate controls. The T1R2- KO deficient mice lacked functional sweet taste receptors and thus could not taste saccharin. Both groups were randomly assigned to drinking water with saccharin or water only for an additional 10 weeks.
In the mice study, neither of the saccharin doses affected the glucose or hormonal responses to an oral glucose tolerance test (OGTT) or glucose absorption. In both the human and mice studies, the supplementation with pure saccharin did not alter microbial diversity or composition at any taxonomic level. In addition, saccharin did not alter concentrations of fecal metabolites or short chain fatty acids (SCFA). However, compared to wild type controls, T1R2-KO mice were protected from age-dependent increases in fecal SCFA as well as the development of glucose intolerance.
Researchers point out that while short-term saccharin consumption at maximum acceptable levels was not sufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans and mice, the negative saccharin effect does not necessarily contradict previous research showing some harmful effects of NCAS. In addition, high NCAS consumption may have harmful effects due to other pathophysiological or lifestyle parameters that have not yet been studied; therefore, future research should target these concerns. While this study supports the recommended safe use of saccharin for healthy consumers that wish to substitute dietary sugars for weight management or caloric control, the study cannot be generalized to other populations or to other market available noncaloric artificial sweeteners.
Source: Serrano, Joan, Kathleen R. Smith, Audra L. Crouch, Vandana Sharma, Fanchao Yi, Veronika Vargova, Traci E. LaMoia et al. “High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice.” Microbiome 9, no. 1 (2021): 1-18.
© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/)
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Posted February 16, 2021.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
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- Serrano J, Smith KR, Crouch AL, et al. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. 2021;9(1):11.
- Joint FAO/WHO Expert Committee on Food Additives. Evaluation of certain food additives and contaminants: forty-first report of the Joint FAO. World Health Organization; 1993.
- Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27-31.
