Get inspired by a weekly roundup on living well, made simple. Sign up for CNN’s Life, But Better newsletter for information and tools designed to improve your well-being.
CNN
—
A growing body of evidence has increasingly linked diet sodas and other no- or low-calorie foods with weight gain — so much so that the World Health Organization issued an advisory in May 2023 saying not to use sugar substitutes for weight loss.
“Replacing free sugars with non-sugar sweeteners does not help people control their weight long-term,” Dr. Francesco Branca, director of WHO’s department of nutrition and food safety, said at the time.
Now, a new study may shed light on why consuming too much of the artificial sweetener sucralose could be counterproductive. Instead of the brain sending a signal to eat less, sucralose triggers an increase in appetite when consumed in a drink.
“Sucralose activates the area in the brain that regulates hunger, and that activation, in turn, is linked to greater ratings of hunger,” said lead study author Dr. Katie Page, an associate professor of medicine and pediatrics and director of the Diabetes and Obesity Research Institute at the University of Southern California’s Keck School of Medicine in Los Angeles.
In fact, people who drank water with sucralose said their appetite increased by nearly 20% compared with drinking water with table sugar, Page said.
In the United States, sucralose is a key ingredient in some Splenda sugar substitutes. In Europe, sucralose is known as E955 and is found in sugar substitutes sold under the brand names Candys, Canderel Yellow, Cukren, Nevella, Splenda, SucraPlus, Sukrana and Zerocal.
The study only investigated the impact of sucralose and did not research other popular artificials sweeteners such as aspartame, acesulfame-K and sodium saccharin.
“This is a very high quality study, using state of the art methods and careful analysis,” said Dr. David Katz, a specialist in preventive and lifestyle medicine, via email. Katz, founder of the nonprofit True Health Initiative, a global coalition of experts dedicated to evidence-based lifestyle medicine, was not involved in the study.
The authors interpreted their results carefully yet make a strong case that “non-caloric sweeteners, and sucralose specifically, interfere with normal appetite regulation in ways that could have adverse effects on weight control and health,” Katz said.
A spokesperson for Heartland Food Products Group, which manufactures Splenda, said that low-calorie and zero-calorie sweeteners are backed by research and expert recommendations.
“Low- or zero-calorie sweeteners like sucralose are recommended by healthcare professionals, food safety experts and credible health organizations for diabetes and weight management based on trusted scientific research showing that the impact of low- or zero-calorie sweeteners on body weight is similar to that of water, and that sweet-tasting products have decreased the want for additional sweets while also helping people manage weight, reduce intake of calories from added sugars, and manage blood sugar levels,” the spokesperson wrote via email.
The idea that artificial sweeteners may be increasing hunger signals from the mammalian brain isn’t new — a prior study coauthored by Page found women and people with obesity were especially sensitive.
“Animal studies have hinted at some of these effects,” Katz said. However, “this is, to my knowledge, the most decisive study to date in humans of direct effects on the appetite center.”
All cells in the body require glucose for energy. The brain is the biggest user, gobbling up to half of all sugars circulating in the blood. Nature, however, designed the brain to respond to natural sugars such as glucose found in whole fruits and some vegetables.
Artificial sweeteners, therefore, appear to confuse the brain, Page said, by sending signals of sweetness without delivering the needed calories the brain requires. Scientists have hypothesized that when those promised calories don’t arrive, the brain may send out a signal to eat more.
The new study, published Wednesday in the journal Nature Metabolism, asked 75 people to consume one of three drinks on three separate occasions: plain water, water sweetened with table sugar (sucrose), and water sweetened with sucralose.
During each visit, the research team tested participants’ fasting blood sugar levels, followed by a brain scan called Functional Magnetic Resonance Imaging, or fMRI, which tracks blood flow to capture activity in different regions of the brain.
“They came out of the scanner and consumed one of the three drinks, and went back into the scanner,” Page said.
One glass contained 300 milliliters of water and 75 grams (about 2.5 ounces) of sugar (sucrose), which is the equivalent of a 16-ounce can of sugary soda, Page said.
Another drink contained enough sucralose to match that sweetness. Sucralose is about 600 times sweeter than sugar, according to the US Food and Drug Administration. The third drink was plain water, which served as a control.
During the brain scanning, Page and her team did another round of blood sampling at 10 minutes, 35 minutes and 120 minutes after consuming the drink and asked participants to rate their hunger level.
“(The study) is particularly strong because it used repeated measures within the same participants and included different methods such as brain imaging, blood draws, and subjective ratings to test their hypothesis,” said Kyle Burger, a scientist at the nonprofit Monell Chemical Senses Center in Philadelphia, which investigates human senses of taste and smell. Burger was not involved in the study.
In addition to finding that drinks with sucralose increased the sensation of hunger by about 17%, Page and her team found increased connections to other parts of the brain responsible for controlling motivation.
“Sucralose appears to affect your decision-making skills,” Page said. “For example, we found increased brain connectivity between the hypothalamus and the anterior cingulate cortex, which controls the risks and rewards of a decision.”
In addition, blood tests showed sucralose had no effect on hormones the brain uses to tell when we are satisfied and no longer hungry, Page said.
“There’s no signal, no signal at all,” she said. “There’s a sweetness signal, but there’s no hormone signal telling you you’re full. Sucralose doesn’t have an effect on those hormones.”
Not everyone, however, may feel the combined effects of sucralose in the same way, Katz said.
“Those with insulin resistance, for instance, may be especially prone to disruption of normal appetite control with sucralose,” he said.
Recommendations on how to manage the body’s reactions to artificial sweeteners are currently complex, Page said. For example, the American Diabetes Association tells people with insulin resistance and diabetes to use no-calorie drinks and foods, but sparingly.
“I’m an endocrinologist so I see patients for diabetes and obesity,” Page said. “I would never say drink or eat more sugar.
“Instead, I tell my patients to not rely on non-caloric sweeteners as a substitute for sugar and try to reduce the overall intake of dietary sweeteners in general,” she said.
Katz agreed, preferring to suggest a form of taste bud “rehab” that can reduce overall use of sugars, no matter what their form.
“A truly wholesome diet has little added sugar in the first place, and thus no sugar to ‘replace’ with sucralose and related compounds,” Katz said.
Just as many people have cut their use of salt, it’s possible to cut your use of sweeteners by teaching taste buds to desire fewer sweets, he said. Taste buds will respond by finding sugary foods that used to be delicious now cloyingly sweet, or in the case of sodium, much too salty, research has shown.
Start out by finding hidden sources of sugar in foods you may not realize are sweetened, Katz told CNN in a prior interview.
“If I asked you to boycott all the desserts in your life, you would probably rebel or fail,” Katz said. “But there is a massive amount of added sugar and sweeteners hiding in foods that are not sweet — in salad dressing, pasta sauce, bread, crackers, even salty chips.”
By choosing products without sweeteners, he said, it’s possible to reduce a person’s daily intake of sugar or sweeteners “by a third, maybe even a half as many grams a day before we even lay a hand on anything that you actually expect to be sweet.”
