Artificial sweeteners may disrupt the body's ability to regulate blood sugar, causing metabolic changes that can be a precursor to diabetes, researchers are reporting.
That is "the very same condition that we often aim to prevent" by consuming sweeteners instead of sugar, said Dr. Eran Elinav, an immunologist at the Weizmann Institute of Science in Israel, at a news conference to discuss the findings.
The scientists performed a multitude of experiments, mostly on mice, to back up their assertion that the sweeteners alter the microbiome, the population of bacteria that is in the digestive system.
The different mix of microbes, the researchers contend, changes the metabolism of glucose, causing levels to rise higher after eating and to decline more slowly than they otherwise would.
The findings by Dr. Elinav and his collaborators in Israel, including Eran Segal, a professor of computer science and applied mathematics at Weizmann, are being published Wednesday by the journal Nature.
Cathryn R. Nagler, a professor of pathology at the University of Chicago who was not involved with the research but did write an accompanying commentary in Nature, called the results "very compelling."
She noted that many conditions, including obesity and diabetes, had been linked to changes in the microbiome. "What the study suggests," she said, "is we should step back and reassess our extensive use of artificial sweeteners."
Previous studies on the health effects of artificial sweeteners have come to conflicting and confusing findings. Some found that they were associated with weight loss; others found the exact opposite, that people who drank diet soda actually weighed more.
Some found a correlation between artificial sweeteners and diabetes, but those findings were not entirely convincing: Those who switch to the products may already be overweight and prone to the disease.
While acknowledging that it is too early for broad or definitive conclusions, Dr. Elinav said he had already changed his own behavior.
"I've consumed very large amounts of coffee, and extensively used sweeteners, thinking like many other people that they are at least not harmful to me and perhaps even beneficial," he said. "Given the surprising results that we got in our study, I made a personal preference to stop using them.
"We don't think the body of evidence that we present in humans is sufficient to change the current recommendations," he continued. "But I would hope it would provoke a healthy discussion."
In the initial set of experiments, the scientists added saccharin (the sweetener in the pink packets of Sweet'N Low), sucralose (the yellow packets of Splenda) or aspartame (the blue packets of Equal) to the drinking water of 10-week-old mice. Other mice drank plain water or water supplemented with glucose or with ordinary table sugar. After a week, there was little change in the mice that drank water or sugar water, but the group getting artificial sweeteners developed marked intolerance to glucose.
Glucose intolerance, in which the body is less able to cope with large amounts of sugar, can lead to more serious illnesses like metabolic syndrome and Type 2 diabetes.
When the researchers treated the mice with antibiotics, killing much of the bacteria in the digestive system, the glucose intolerance went away.
At present, the scientists cannot explain how the sweeteners affect the bacteria or why the three different molecules of saccharin, aspartame and sucralose result in similar changes in the glucose metabolism.
To further test their hypothesis that the change in glucose metabolism was caused by a change in bacteria, they performed another series of experiments, this time focusing just on saccharin. They took intestinal bacteria from mice who had drank saccharin-laced water and injected them in mice that had never been exposed any saccharin. Those mice developed the same glucose intolerance. And DNA sequencing showed that saccharin had markedly changed the variety of bacteria in the guts of the mice that consumed it.
Next, the researchers turned to a study they were conducting to track the effects of nutrition and gut bacteria on people's long-term health. For 381 nondiabetic participants in the study, the researchers found a correlation between the reported use of any kind of artificial sweeteners and signs of glucose intolerance. In addition, the gut bacteria of those who used artificial sweeteners were different from those who did not.
Finally, they recruited seven volunteers who normally did not use artificial sweeteners and over six days gave them the maximum amount of saccharin recommended by the United States Food and Drug Administration. In four of the seven, blood-sugar levels were disrupted in the same way as in mice.
Further, when they injected the human participants' bacteria into the intestines of mice, the animals again developed glucose intolerance, suggesting that effect was the same in both mice and humans.
"That experiment is compelling to me," Dr. Nagler said.
Intriguingly — "superstriking and interesting to us," Dr. Segal said — the intestinal bacteria of the people who did experience effects were different from those who did not. This suggests that any effects of artificial sweeteners are not universal. It also suggests probiotics — medicines consisting of live bacteria — could be used to shift gut bacteria to a population that reversed the glucose intolerance.
Dr. Frank Hu, a professor of nutrition and epidemiology at the Harvard School of Public Health who did not take part in the study, called it interesting but far from conclusive and added that given the number of participants, "I think the validity of the human study is questionable."
The researchers said future research would examine aspartame and sucralose in detail as well as other alternative sweeteners like stevia.
An article Thursday about the effect of artificial sweeteners on metabolism misstated the title of a researcher who commented on the study. Dr. Frank Hu is a professor of nutrition and epidemiology, not immunology, at the Harvard School of Public Health.
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