Now, a new study published in the journal Nature introduces a new idea: Diet sodas may alter our gut microbes in a way that increases the risk of metabolic diseases such as Type 2 diabetes — at least in some of us.
In the paper, researchers at the Weizmann Institute of Science in Israel describe what happened when they fed zero-calorie sweeteners, including saccharin, aspartame and sucralose, to mice.
"To our surprise, [the mice] developed glucose intolerance," Weizmann researcher Eran Elinav tells us.
Intrigued by the findings, Elinav and his colleague Eran Segal set out to determine if this might happen in people as well.
First, they analyzed data collected from a group of about 400 people who are enrolled in an ongoing nutrition study. They found that people who were heavy consumers of artificial sweeteners had slightly elevated HbA1C levels (a long-term measure of blood sugar) — compared with people who rarely or never consumed artificial sweeteners.
Next, they recruited seven volunteers — people who were not in the habit of drinking diet drinks — and asked them to start consuming the equivalent of 10-12 of those fake sugar packets during a one-week experiment.
"What we find is that a subgroup [four of the seven people] developed significant disturbances in their blood glucose even after short-term exposure to artificial sweeteners," Elinav says.
For example, results of a glucose tolerance test found that some individuals' blood sugar temporarily shot up to levels that are characterized as pre-diabetic within just a few days of introducing the artificial sweetener.
"This was a surprise to us," Elinav says.
And how it's happening may be even more surprising. Their experiments showed that artificial sweeteners can alter the mix of bacteria in the guts of mice and people in a way that can lead some to become glucose intolerant.
"I found this work exciting, because to me it's a new idea," says physician Martin Blaser, who directs the Human Microbiome Program at New York University.
After reading the paper, he says: "I can just tell you, ... as a middle-aged man who's concerned about his diet and his waistline — and [as] somebody who drinks diet soda — I didn't drink any yesterday."
While the findings are preliminary, the paper could begin to explain why studies of diet soda point in opposite directions.
"All of us have a microbiome," made up of trillions of organisms. "[It's] extremely complex. Everybody's microbiome is a little different," Blaser says.
And the ways our microbiomes respond to what we eat can vary, too.
In the study, the Israeli researchers find that as mice and people started consuming artificial sweeteners, some types of bacteria got pushed out, and other types of bacteria began to proliferate.
It could be that for some people who responded negatively to the artificial sweetener, the bacteria that got crowded out were helping to keep glucose in check.
How it's happening isn't clear, and Blaser says a lot more research is needed.
"So that's the next step," Blaser says. "Firstly, for [researchers] to confirm this, to see if it's really true." And the next challenge is to understand the mechanism. "How does the change in the microbial composition — how is it causing this?"
Lots of researchers agree they'd like to see a large-scale study.
"It's much too early, on the basis of this one study, [to conclude that] artificial sweeteners have negative impacts on humans' [risk for diabetes]," says James Hill, director of the Center for Human Nutrition at the University of Colorado.
He points to a randomized controlled trial published in 2011 that found artificial sweeteners helped to limit the rise in blood sugar in a group of slightly overweight people, compared with sugar.
Hill also points to a study of people on the National Weight Control Registry that found successful long-term dieters tend to consume artificially sweetened foods and beverages at a higher rate compared with the general population.
So expect the debate over diet sodas to continue — and also anticipate hearing more about the role of our microbiomes.
It's clear that our gut microbes are not just passive organisms hitching a ride on our bodies, says Kirsten Tillisch, a gastroenterologist at the University of California, Los Angeles. "They're affecting our health in active and powerful ways."
Tillisch's take on the new research: It's hypothesis-generating.
She says many patients come in asking about diet sodas. Some keep drinking them, even while complaining that diet drinks give them headaches or make them feel bloated.
Her solution: Drink water instead.