• Posted March 28, 2025

Sugar Substitute Appears To Boost Appetite, Hunger

Splenda doesn’t directly add calories to your diet, but the sweetener still might lead people to pack on pounds, a new study says.

The sugar substitute might spur on a person’s appetite and feelings of hunger, potentially leading them to overeat, according to results published March 26 in the journal Nature Metabolism.

Splenda’s main ingredient, sucralose, appears to confuse the brain by providing a sweet taste without also delivering the calories one would expect, senior investigator Dr. Kathleen Page, director of the University of Southern California Diabetes and Obesity Research Center, said in a news release.

“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,” she said.

About 40% of Americans regularly consume sugar substitutes, usually as a way to reduce their sugar intake, researchers said in background notes.

“But are these substances actually helpful for regulating body weight?” Page asked. “What happens in the body and brain when we consume them, and do the effects differ from one person to the next?”

To explore this further, researchers tested how 75 people responded after consuming water, a drink sweetened with sucralose or a drink sweetened with regular sugar.

The team collected MRI brain scans, blood samples and hunger ratings from participants both before and after they consumed each drink. Participants drank each of the three at different times.

Compared to either water or a sugary beverage, sucralose increased activity in the hypothalamus, a brain region that regulates appetite and body weight, results show.

Sucralose also prompted increased connectivity between the hypothalamus and several brain areas involved with motivation and sensory processing. This suggests that sucralose could impact cravings or eating behavior, Page said.

In addition, sucralose increased people’s self-reported feelings of hunger compared to when they drank a sugary beverage, but not compared to water, researchers noted.

All these effects were strongest in people with obesity, researchers noted.

Blood tests showed that drinking sugar led to increases in blood sugar levels and the hormones that regulate those levels, including insulin and glucagon-like peptide 1 (GLP-1), the hormone mimicked by cutting-edge weight loss drugs.

Drinking sucralose had no effect on those same hormones, results show.

“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.”

Researchers said future studies should look into whether these changes in brain and hormone activity have any long-term effects on a person’s weight. 

Children and teenagers might be particularly vulnerable to such impacts, given how much sugar and sugar substitutes they eat compared to other age groups, Page said.

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

More information

The Cleveland Clinic has more on sucralose.

SOURCE: University of Southern California, news release, March 26, 2025