Brief High-Dose Saccharin Seems Safe, but Jury Out on Long-Term Use

Marlene Busko

January 29, 2021

Consuming the maximum acceptable daily intake of the noncaloric artificial sweetener saccharin for 2 weeks did not alter gut microbiota diversity or composition, or induce glucose intolerance, in 23 healthy young men and women.

And consuming four times this dose of saccharin for 10 weeks did not alter these outcomes in mice, in a study recently published online in Microbiome.

"We clearly show that short-term saccharin supplementation per se is insufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans and mice consuming typical ad libitum diets," Joan Serrano, PhD, a researcher in the department of biological chemistry and pharmacology at Ohio State University, Columbus, and colleagues write.

Saccharin "is likely safe for healthy consumers that wish to substitute dietary sugars for weight management or caloric control," they summarize.

But they caution, "our null findings do not necessarily contradict previous reports showing some harmful metabolic effects."

And "this does not preclude the possibility that years of chronic saccharin use may eventually lead to slow maladaptive responses or predispose consumers to the development of disease," they add.

"We Just Don't Know"

The researchers say that interventional studies that isolate and identify the underlying physiologic or lifestyle conditions that may make noncaloric artificial sweetener use harmful are needed.

Meanwhile, "at the current state of knowledge, caution should be practiced" by consumers, senior author George Kyriazis, PhD, also of Ohio State University, told Medscape Medical News in an email.

Similarly, Eran Elinav, MD, PhD, from the Weizmann Institute of Science, Rehovot, Israel — who is senior author of an article published in Nature in 2014 by Jotham Suez and colleagues, which was part of the impetus for the current study — also calls for more research and advises caution.

The Israeli group found that saccharin intake was associated with altered gut microbiota and induced glucose intolerance in four of seven healthy young adults (who had different microbiomes at baseline), and in mice fed normal chow or a high-fat diet, compared with control mice who consumed sugary water, as reported at the time by Medscape Medical News.  

There have been "dozens of published works in the past decade, convincingly demonstrating (in bacterial cultures, mice, rats, dogs, and piglets...) that non-nutritive sweeteners may not be inert in their intersections with the microbiome and/or the mammalian host, as was originally claimed," Elinav told Medscape Medical News in an email.

"Different individuals featuring unique microbiome and physiological traits may feature unique metabolic response patterns, even when consuming identical foods, sweeteners included," he continued, stressing this needs to be studied in future trials.

According to Elinav, "Until such decisive knowledge on the impacts of non-nutritive sweeteners on human physiology is obtained and assessed, our view is that caution and healthy skepticism should be practiced, while consumption of water should be regarded" as the best option.

David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, who wrote a 2016 commentary in Medscape Medical News about Suez and colleagues' study, said the earlier study and the current one "are conflicting and both seemingly done very well."

"Artificial sweeteners used on a conservative basis may not be as harmful as supposed, but we just don't know," he observed.

"Using them [in a way that will] minimize exposure until we know more may be the best recommendation, particularly in patients who have obesity and diabetes," according to Johnson, "and there is maybe not as strong a signal here for healthy young people."

But many do go overboard, he told Medscape Medical News, noting some people, "drink six diet Cokes a day."

"Good judgment, good diet is probably the best recommendation."

Risk of Diabetes or Metabolic Syndrome?

The US Food and Drug Association (FDA) has approved six noncaloric artificial sweeteners — saccharin, aspartame, acesulfame potassium (Ace-K), sucralose, neotame, and advantame — and an estimated 25% of children and 41% of adults in the United States currently consume them daily, Serrano and colleagues write.

However, over the past 30 years several epidemiologic studies reported that these food additives may be linked to greater risks of type 2 diabetes or metabolic syndrome, and some animal studies linked them to decreased gut microbiota diversity.

In 2014, Suez and colleagues established a causal relationship between saccharin consumption and the development of glucose intolerance through adverse changes in gut microbiota in young, healthy, lean humans, and in mice.

The current study aimed to build on this, Kyriazis explained, and also investigated whether sweet taste receptors in the intestine might play a role in outcomes.

They identified 46 healthy, young lean men and women who did not use artificial sweeteners or have diabetes or other conditions that might affect metabolic function.  

The participants were randomized into four roughly equal groups.

They consumed their usual diet plus gelatin capsules containing saccharin (400 mg/day) or lactisole (an inhibitor of sweet taste receptors, 670 mg/day) or saccharin and lactisole, or placebo for 2 weeks followed by 2 weeks of placebo.

The maximum acceptable daily intake of saccharin is 5 mg/kg body weight, which corresponds to 400 mg/day for an average 80 kg individual, equal to 11 packets of 36-mg saccharin (Sweet and Low), Kyriazis explained.

The 32 women and 14 men were a mean age of 25-33 years and had a mean BMI of 21-23 kg/m2. They had 75-g oral glucose tolerance tests at study entry and at 2 and 4 weeks.

The participants who consumed saccharin did not have changes in glucose tolerance or gut microbiota, nor did those who consumed lactisole.

The latter suggests the role of the sweet taste receptors was "obscured, irrelevant, or untestable," the researchers conclude.

The study was supported by the National Institutes of Health, the National Institute of Food and Agriculture, and Advent Health. Johnson and the authors of both studies have reported no relevant financial disclosures.

Microbiome. Published online January 12, 2021. Full text

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