The sour side of artificial sweeteners

In this sweet, sweet world we live in, losing weight can be a dull and flavorless experience. Lovely stove-popped popcorn drenched in butter gives way to dry microwaved half-burnt kernels covered in dusty yellow powder. The cookies and candy that help us get through the long afternoons are replaced with virtuous but boring apples and nuts. Even the sugar that livens up our coffee gets a skeptical eye: That’s an extra 23 calories per packet you shouldn’t be eating.

What makes life sweet for those of us who are counting calories is artificial sweeteners. Diet soda gives a sweet carbonated fix. A packet of artificial sweetener in your coffee or tea makes it a delicious morning dose.

But a new study, published September 17 in Nature, found that the artificial sweetener saccharin has an unintended side effect: It alters the bacterial composition of the gut in mice and humans. The new bacterial neighborhood brings with it higher blood glucose levels, putting the humans and the murine counterparts at risk for diabetes.

Many people wondered if the study’s effects were real. We all knew that sugar was bad, but now the scientists are coming for our Splenda! It seems more than a little unfair. But this study was a long time coming. The scientific community has been studying artificial sweeteners and their potential hazards for a long time. And while the new study adds to the literature, there are other studies, currently ongoing and planned for the future, that will determine the extent and necessity of our artificially sweetened future.

“[The study of artificial sweeteners] is a field that’s had several peaks,” explains Susan Swithers, a behavioral neuroscientist at Purdue University in West Lafayette, Ind. “Since the 1980s people have had concerns that artificial sweeteners could have negative effects. You couldn’t have your fake cake and eat it, too.” But studies on artificial sweeteners had varied results, often depending on who paid for the work, she says: “If it was funded by artificial sweetener companies it was good, if it was funded by sugar companies it was bad.”

Gradually, government-funded studies began to come out. Many of these were epidemiological studies, collecting observations about a slice of a population and studying the metabolic health of those who ate or drank artificial sweeteners versus those who didn’t. A 2008 paper in Obesity showed that those who used artificial sweeteners gained more weight over a seven- to eight-year period than those who did not. A 20-year study of young adults in a cardiovascular health study published in February 2012 in the American Journal of Clinical Nutrition showed that those who consumed diet beverages ran a slightly higher risk of metabolic problems than their non-artificial-sweetener-eating counterparts, even if they kept a “prudent” diet high in nuts and whole grains. It was enough, says pediatric endocrinologist Kristina Rother of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., to conclude that “these artificial sweeteners are not inert.”

Eran Segal is a computational biologist at the Weizmann Institute of Science in Rehovot, Israel. He co-led the recent Nature study together with Eran Elinav. Segal says that many epidemiological studies over the years have pointed to “positive associations between artificial sweeteners and obesity and diabetes.” But he notes that studies of large populations can only show you associations, and notes, “it’s hard to tease out cause and effect.”

And studies finding benefits to artificial sweeteners add complexity to the issue. A 2010 study published in the journal Appetite examined the effect of stevia, aspartame and the natural sugar sucrose and found that consuming drinks sweetened with the artificial sweeteners before lunch and dinner resulted in less overall food consumption compared with drinks sweetened with sucrose. A study in Dutch schoolchildren published in 2012 in the New England Journal of Medicine showed that kids who drank one extra sugar-sweetened beverage per day for 18 months gained more weight than those drinking a beverage artificially sweetened with sucralose and acesulfame potassium. Another study published in April in the American Journal of Clinical Nutrition showed overweight people given artificial sweeteners to supplement their normal diet lost weight compared with those given additional sucrose. Sweeteners might not be inert, but they seemed better than straight sugar.

But some animal studies have been telling a different story. Swithers reported in the August 2009 Behavioral Neuroscience that rats receiving yogurt with the artificial sweeteners saccharin or acesulfame potassium gained more weight than rats receiving the same yogurt sweetened with glucose. She also published a study in July 2012 in Behavioral Brain Research showing that feeding saccharin-sweetened yogurt to rats produced higher blood glucose levels after two weeks than did the same yogurt sweetened with glucose. Another group reported in 2012 in PLOS ONE that lifelong aspartame produced insulin resistance and high blood glucose levels in mice.

Even the microbiome has come under the artificial sweetener microscope. While at Duke University, Susan Schiffman and her laboratory gave Splenda to rats, focusing on doses at, above and below the Food and Drug Administration–recommended limits for the main compound, sucralose. The artificial sweetener changed the gut microbiome at every dose, with a reduction in beneficial gut bacteria such as lactobacilli, the researchers reported in 2008 in the Journal of Toxicology and Environmental Health.

If all of this work has been out there, why do we feel so blindsided? Has the media been ignoring artificial sweeteners for so long? Far from it. Every time a new article on the potential negative effects artificial sweeteners comes out, it receives extensive media coverage. Outlets including Science News, the Los Angeles Times, the New York Times, Globe and Mail, National Public Radio’s Science Friday and Wired magazine  cover the studies. And every time, it seems to catch people by surprise. So far, it seems like the science on artificial sweeteners has gone, well, right through us.

But the new study in Nature proposes the beginnings of a mechanism. Artificial sweeteners change the gut microbe balance. The gut microbe change leads to higher blood glucose level. But how the artificial sweeteners are altering gut microbes remains obscure. Segal says that his study found increases in bacteria that produce short-chain fatty acids, chemicals that could “be precursors to increased fat storage.” He also notes that bacterial species from the genus Bacteroides increase after both short- and long-term saccharin exposure. “This family of bacteria has pathways that could allow them to extract more energy from our food,” he explains. “They are also linked with diabetes and obesity.”

Swithers says that gut microbiota may be only one piece of the blood glucose puzzle. “It could be a change in microbiome, it could be how we predict that sweet things will have calories, it could even include cognitive distortions [in how we think of food],” she says. “We need to conduct more studies, uncover possibly multiple mechanisms.” This will probably mean more trials in rodents and other animal models to determine exactly how the body and brain respond to artificial sweeteners.

Now is also the time for more clinical studies, notes Rother, who is currently recruiting participants for a clinical study on artificial sweeteners. “We need to do good human studies,” she says. “We need to apply the right techniques and have good control groups to figure this out.”

As more and more studies in humans and in animals come to the fore, it’s possible that a more complex picture of artificial sweeteners will emerge. The sweeteners may be better for some people than others, and their use may depend on a person’s individual health profile and prospects. But this latest study did not come out of nowhere. It builds upon a growing literature that suggests our dieting life may not need to be so artificially sweet.