The findings, published in the journal Nature, were based on a series of experiments in mice, as well as a small study of humans.
The team of researchers included Dr. Eran Elinav, an immunologist, and Eran Segal, a professor of computer science at Israel's Weizmann Institute of Science. The researchers contend that zero calorie sweeteners, such as saccharin, sucralose, and aspartame, can change the gut microbiome, the population of helpful bacteria that live in our digestive system.
This disruption can lead to higher blood sugar levels. When the body can’t cope with large amounts of sugar, metabolic syndrome and type 2 diabetes can develop.
Although many people use artificial sweeteners to lose weight, increased blood glucose levels can raise the risk of serious complications for people with type 2 diabetes. These complications include heart disease, blindness, and nerve and kidney damage.
Artificial Sweeteners Not So Sweet for Glucose Intolerance
Speaking to Healthline, Segal said, “We found that consumption of the artificial sweeteners in mice and humans can induce this state of glucose intolerance, which is one of the hallmarks of metabolic syndrome. A standard test you do to diagnose people with prediabetes or diabetes is to let them consume sugar, and then track their blood sugar levels for two hours. A normal response would be a rise in blood sugar levels and then a return to normal within about two hours. An abnormal response would be much more elevated.”
Segal went on to explain that consuming artificial sweeteners “seem[s] to have an adverse metabolic effect, which goes against how they are being advertised. If you look at the guidelines of the American Diabetes Association or American Heart Association, they recommend use of artificial sweeteners as having benefits for weight loss and management of diabetes and blood sugar levels. We looked at these same parameters, and found they are having a harmful effect.”
The researchers conducted a series of experiments in mice. The first involved giving mice artificial sweeteners to see if they developed glucose intolerance. The second involved putting the gut bacteria of mice who consumed sweeteners into the guts of sterile, bacteria-free mice who had never eaten artificial sweeteners. The third involved adding artificial sweeteners to healthy bacteria, then growing the bacteria and putting them into the guts of sterile mice.
“All three cases led to the same conclusion and observation — that the bacteria were inducing glucose intolerance. The sweeteners were altering the bacteria, which induced glucose intolerance,” said Segal.
Human Study Small but Revealing
The researchers also looked at 400 people from another of their studies, called the Personalized Nutrition Project. The participants were divided into groups of those who consumed artificial sweeteners and those who did not.
“We found those who consume artificial sweeteners basically have a marker in their blood that indicates they are more prone to diabetes; they have this metabolic syndrome condition,” said Segal.
The researchers also conducted a small-scale interventional study, asking seven people who do not normally consume artificial sweeteners to consume these products for one week.
“After just one week of consumption of sweeteners, four persons developed the glucose intolerance phenotypes, and when transferring their microbes to sterile mice, that also induced the glucose intolerance,” said Segal.
Segal acknowledges that the interventional study was just a start.
“We are calling for further studies to be performed in an interventional way," Segal said. "Based on the current massive and unsupervised use and official recommendations to use sweeteners, we are calling for a reassessment of these recommendations, together with further studies that will examine their effect ... People are intelligent and will make their own personal choices. It’s too early to draw massive conclusions on the use of artificial sweeteners, but the current guidelines should definitely be reassessed.”
Experts Size Up the Study Results
Commenting on the findings, Dr. Gerald Bernstein, director of the Diabetes Management Program at the Friedman Diabetes Institute at Mount Sinai Medical Center, told Healthline, “The interesting observation of the relationship between artificial sweeteners and glucose intolerance in animals and some humans opens up an area worth exploring ... For years, most obese patients who developed type 2 diabetes drank regular sugared soda such as Coke, Pepsi, or RC Cola. After a visit to the healthcare team, they switched to artificial sweeteners in their drinks. This removed a significant amount of calories from their daily intake and facilitated weight loss.”
Bernstein said he won't stop drinking his daily diet soda, and that while the findings are interesting, he agreed more work is needed “to clarify the specifics, not so much of glucose metabolism, but what is going on with insulin.”
Dr. Ruth Loos, a professor of preventive medicine at the Icahn School of Medicine at Mount Sinai, also weighed in. She told Healthline, “Artificial sweeteners have been controversial for some time, and there are still no conclusive, large intervention studies. When products have artificial sweeteners, it is stated on the package if you use too much it can cause bloat, so we know it affects our gut microbes.”
Loos went on to say that the few interventional studies that have been done show artificial sweeteners have a beneficial effect on weight.
"If you have a beneficial effect on weight, then the glucose response is more optimal," she said. "[Segal's] studies in mice seemed pretty convincing. The results in humans are totally not ... A trial is a very controlled, standardized study, but their study is not. They showed high users of artificial sweeteners have higher fasting sugar levels, but this is observational. Who are the people who typically use artificial sweeteners? Very often it’s obese people who try to lose weight and usually have higher sugar levels."
Loos is concerned that the study results could cause confusion among people about whether they should stop using sugar substitutes. She said that of the seven human participants in Segal's study, the three who responded poorly already showed a poorer response to glucose before they started taking artificial sweeteners.
"Their microbiome was different from the four other people. Maybe they were susceptible already, and the artificial sweeteners were the trigger that made something worse," she said. "It’s a nice preliminary study, but definitely there needs to be a follow-up to confirm or refute it. The important message here is, we should not tell people to stop using artificial sweeteners. There is not enough evidence to say to people, 'Stop using it.'"
FDA Approves New Weekly Diabetes Injection
In a separate development, the Food and Drug Administration (FDA) has approved dulaglutide, a once-weekly injection to improve blood sugar control, along with diet and exercise, in adults with type 2 diabetes. The drug is manufactured by Eli Lilly and Company and will be sold under the name Trulicity.
“Type 2 diabetes is a serious chronic condition that causes blood glucose levels to rise higher than normal. Trulicity is a new treatment option, which can be used alone or added to existing treatment regimens to control blood sugar levels in the overall management of type 2 diabetes,” said Dr. Mary Parks, deputy director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, in a press statement.
Trulicity is a glucagon-like peptide-1 (GLP-1) receptor agonist, a hormone that helps normalize blood sugar levels. The drug’s safety and effectiveness were evaluated in six clinical trials in 3,342 patients with type 2 diabetes. Patients receiving Trulicity saw an improvement in their blood sugar control as well as reductions in HbA1c levels.
A boxed warning for Trulicity states that tumors of the thyroid gland have been observed in mouse studies of Trulicity, but doctors don't know whether Trulicity causes thyroid tumors in humans.
The FDA is requiring several post-marketing safety studies of Trulicity.