Study contradicts earlier findings on saccharin-for-sugar substitution and diabetes

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For those trying to live a healthy lifestyle, the choice between sugar and artificial sweeteners such as saccharin can be confusing. A new study led by researchers at The Ohio State University Wexner Medical Centre and The Ohio State University College of Medicine found the sugar substitute saccharin doesn't lead to the development of diabetes in healthy adults as previous studies have suggested.

"It's not that the findings of previous studies are wrong, they just didn't adequately control for things like underlying health conditions, diet choices and lifestyle habits," said George Kyriazis, assistant professor of biological chemistry and pharmacology at Ohio State and senior author of the study. "By studying the artificial sweetener saccharin in healthy adults, we've isolated its effects and found no change in participants' gut microbiome or their metabolic profiles, as it was previously suggested."

Kyriazis collaborated with researchers at Ohio State's College of Food, Agricultural & Environmental Sciences, Ohio State's College of Arts and Sciences, Sanford Burnham Prebys Medical Discovery Institute in California and the Translational Research Institute for Metabolism and Diabetes at Advent-Health in Florida.

Non-caloric artificial sweeteners are often consumed as a substitute for dietary sugars, and saccharin is one of six artificial sweeteners approved by the US Food and Drug Administration.

The use of artificial sweeteners has increased dramatically over the past decade due to growing awareness of the negative health outcomes associated with consuming too much sugar, study authors noted.

"Previous studies elsewhere have suggested that consuming artificial sweeteners is associated with metabolic syndrome, weight gain, obesity and non-alcoholic fatty liver disease. These findings have raised concerns that consuming them may lead to adverse public health outcomes, and a lack of well-controlled interventional studies contributed to the confusion," said study first author Joan Serrano, a researcher in the department of biological chemistry and pharmacology at Ohio State.

A total of 46 healthy adults ages 18-45 with body mass indexes of 25 or less completed this randomized, double-blind, placebo-controlled study.

Participants ingested capsules that contained the maximum acceptable daily amount of either saccharin, or lactisole (a sweet taste receptor inhibitor, or saccharin with lactisole or placebo every day for two weeks. The maximum acceptable daily amount of saccharin is 400 milligrams per day, which is far more than the average consumer would consume. The study excluded people with acute or chronic medical conditions or taking medications that could potentially affect metabolic function, such as diabetes, bariatric surgery, inflammatory bowel disease or a history of malabsorption and pregnant or nursing.

Researchers also tested for 10 weeks the effects of even higher dose of saccharin in mice that genetically lack sweet taste receptors with the same results: the artificial sweetener didn't affect glucose tolerance, or cause any significant gut microbiota changes or apparent adverse health effects.

"Sugar, on the other hand, is well-documented to contribute to obesity, heart disease and diabetes," Kyriazis said. "So, when given the choice, artificial sweeteners such as saccharin are the clear winner based on all of the scientific information we currently have."

Future research will study each FDA-approved sweetener individually to examine if there are any differences in how they're metabolised. Researchers will study these substances over a longer period of time to ensure they're safe for daily use.

The National Institutes of Health, the National Institute of Food and Agriculture and Advent-Health institutional funds supported this work.


Study details

High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice

Joan Serrano, Kathleen R Smith, Audra L Crouch, Vandana Sharma, Fanchao Yi, Veronika Vargova, Traci E LaMoia, Lydia M Dupont, Vanida Serna, Fenfen Tang, Laisa Gomes-Dias, Joshua J Blakeslee, Emmanuel Hatzakis, Scott N Peterson, Matthew Anderson, Richard E Pratley, George A Kyriazis

Published in Microbiome in 2021


Non-caloric artificial sweeteners (NCAS) are widely used as a substitute for dietary sugars to control body weight or glycemia. Paradoxically, some interventional studies in humans and rodents have shown unfavorable changes in glucose homeostasis in response to NCAS consumption. The causative mechanisms are largely unknown, but adverse changes in gut microbiota have been proposed to mediate these effects. These findings have raised concerns about NCAS safety and called into question their broad use, but further physiological and dietary considerations must be first addressed before these results are generalized. We also reasoned that, since NCAS are bona fide ligands for sweet taste receptors (STRs) expressed in the intestine, some metabolic effects associated with NCAS use could be attributed to a common mechanism involving the host.

We conducted a double-blind, placebo-controlled, parallel arm study exploring the effects of pure saccharin compound on gut microbiota and glucose tolerance in healthy men and women. Participants were randomized to placebo, saccharin, lactisole (STR inhibitor), or saccharin with lactisole administered in capsules twice daily to achieve the maximum acceptable daily intake for 2 weeks. In parallel, we performed a 10-week study administering pure saccharin at a high dose in the drinking water of chow-fed mice with genetic ablation of STRs (T1R2-KO) and wild-type (WT) littermate controls. In humans and mice, none of the interventions affected glucose or hormonal responses to an oral glucose tolerance test (OGTT) or glucose absorption in mice. Similarly, pure saccharin supplementation did not alter microbial diversity or composition at any taxonomic level in humans and mice alike. No treatment effects were also noted in readouts of microbial activity such as fecal metabolites or shortchain fatty acids (SCFA). However, compared to WT, T1R2-KO mice were protected from age-dependent increases in fecal SCFA and the development of glucose intolerance.

Short-term saccharin consumption at maximum acceptable levels is not sufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans and mice.


The Ohio State University Wexner Medical Centre


Microbiome" target="_blank">




FOCUS: No compelling evidence for the health benefits of non-sugar sweeteners


Sweeteners found toxic to gut microbes


Artificial sweeteners might leave a bitter taste – Systematic review


Sugar sweetener woes for the obese

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