If you’re someone who’s trying to avoid the unwanted calories of sugar, you may be a drinker of diet sodas instead of regular. But a small new study adds to the growing body of evidence that a commonly used zero-calorie sweetener—sucralose, found in sodas and many sweets and snack foods—may be having an unwanted effect: increasing your appetite.
In a randomized trial, 75 young adults of various weights consumed a drink containing sucralose, sugar, or water. Those consuming the sucralose had greater hunger responses, suggesting that non-caloric sweeteners could affect “key mechanisms in the hypothalamus responsible for appetite regulation,” the study, published on March 26 in Nature Metabolism, reported.
By contrast, for the people who consumed a drink with sugar (sucrose), the effect was a reduction of appetite.
To clearly see the results, researchers collected functional magnetic resonance imaging (fMRI) brain scans, blood samples and hunger ratings before and after subjects drank their beverages. Sucralose, they found, increased hunger and activity in the hypothalamus, especially in people with obesity.
Previous studies in rodents have suggested this increase in hunger—and a previous human study supported this, too, finding that women and people with obesity were particularly sensitive. And in 2022 the World Health Organization issued guidance noting that “there is no clear consensus on whether non-sugar sweeteners are effective for long-term weight loss or maintenance.”
In fact, as shown in this latest study, they appear to change how the hypothalamus communicates with other parts of the brain. That might be because sucralose is 600 times sweeter than sucrose but with calorie-free, which might create “a mismatch between the expectation of caloric intake and the absence of actual energy,” lead author Kathleen Alanna Page, from the Keck School of Medicine at the University of Southern California, explained in a news release.
“If your body is expecting a calorie because of the sweetness, but doesn’t get the calorie it’s expecting,” she says, “that could change the way the brain is primed to crave those substances over time.”
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The findings suggest that sucralose could impact cravings or eating behaviors, Page said.
“The body uses these hormones to tell the brain you’ve consumed calories, in order to decrease hunger,” Page said. “Sucralose did not have that effect—and the differences in hormone responses to sucralose compared to sugar were even more pronounced in participants with obesity.”
Sucralose, sold under the brand name Splenda, is approved by the U.S. Food and Drug Association for use in food as a sweetener. Past studies have found it could possibly have links to increased blood sugar and insulin levels, raised cancer risk due to breaking down in heat during the baking process. And recent expert guidance around what drinks should be avoided by kids and teens included those containing sugar substitutes, including sucralose, because “The bottom line is that we don’t have good evidence on the long-term impacts of these sweeteners when it comes to kids’ health and safety.”
Moving forward, the researchers will look into that more closely, as they are beginning a follow-up study to see how calorie-free sweeteners affect the brains of children and adolescents, who consume more sugar and sugar substitutes than any other age group.
“Are these substances leading to changes in the developing brains of children who are at risk for obesity? The brain is vulnerable during this time, so it could be a critical opportunity to intervene,” Page said.
