Researchers at the University of Southern California analyzed brain scans and found that a popular sugar substitute, once thought to help cut calories, might instead be nudging people to eat more.

They found that sucralose, a common ingredient in “diet” drinks and “sugar-free” snacks, alters brain activity tied to hunger—especially in people with obesity. And it doesn’t stop there. Unlike sugar, sucralose fails to trigger the body’s hormonal signals of fullness, potentially leaving people feeling hungrier, not satisfied.

“If your body is expecting a calorie because of the sweetness, but doesn’t get the calorie it’s expecting, that could change the way the brain is primed to crave those substances over time,” Dr. Kathleen Page, lead author of the study and director of the USC Diabetes and Obesity Research Institute told Newsweek.

A Sweet Taste With No Satisfaction

For years, dietitians and food manufacturers have leaned on artificial sweeteners to help consumers trim their sugar intake. Sucralose—sold under brand names like Splenda—is roughly 600 times sweeter than table sugar, but adds no calories. Around 40% of Americans regularly consume sugar substitutes, hoping to avoid the consequences of added sugars.

But as early as 2023, the World Health Organization warned against using non-sugar sweeteners for weight control, citing links to weight gain, diabetes, heart disease, and higher mortality. Yet, scientists still didn’t fully understand how these substances were affecting the brain.

That’s where Page and her team stepped in.

They recruited 75 participants, including people with healthy weight, overweight, and obesity, for a controlled experiment. Each person came to the lab three times. On each visit, they drank either plain water, a sugar-sweetened beverage, or a sucralose-sweetened drink.

Researchers then scanned their brains using functional MRI, drew blood samples, and asked how hungry they felt. Sucralose lit up the hypothalamus, a part of the brain that controls appetite and body weight. The same didn’t happen with sugar or water. Even more telling was how sucralose influenced the hypothalamus to interact more intensely with parts of the brain involved in motivation and decision-making—areas that could influence cravings and impulse eating.

“When people consume something sweet but don’t get the energy they expect, it might increase craving or drive for food,” said Dr. Page. “This could potentially lead to overeating in the long run.”

Hunger Without Hormones

One key difference between sugar and sucralose was what happened in the bloodstream.

After consuming real sugar, participants experienced a spike in blood sugar and appetite-regulating hormones like insulin and GLP-1. These hormones tell the brain: “You’ve eaten. You’re full.”

Sucralose, on the other hand, didn’t trigger these hormones.

“The body uses these hormones to tell the brain you’ve consumed calories, in order to decrease hunger,” said Page. “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.”

Interestingly, these brain and hormonal effects weren’t uniform. Women experienced greater changes in brain activity than men, hinting at a sex-specific response to sweeteners that needs more study.

The research opens up troubling questions, especially for children. Young people are some of the biggest consumers of diet drinks and “sugar-free” snacks. Page’s team has already launched a follow-up study to explore how these products might affect developing brains.

“Are these substances leading to changes in the developing brains of children who are at risk for obesity?” Page asked. “The brain is vulnerable during this time, so it could be a critical opportunity to intervene.”

So, Should We Avoid Sucralose?

This study doesn’t claim that sucralose is harmful—but it adds to a growing body of evidence that artificial sweeteners may not be metabolically neutral.

Earlier rodent studies had suggested that sweeteners might impair normal brain responses to food. This human study confirms similar patterns, but with added nuance: body weight, insulin sensitivity, and sex appear to shape how our brains respond to sweetness without calories.

“Insulin resistance was associated with heightened hypothalamic responses to sucralose,” the authors noted. That could be important for people with prediabetes or metabolic syndrome.

Still, this was an acute study—measuring immediate responses, not long-term outcomes. “More research is needed to determine how repeated exposure affects appetite regulation,” Dr. Page said.

The findings appeared in Nature Metabolism.