A new study from the University of Southern California (USC) has raised concerns about the impact of artificial sweeteners, specifically sucralose, on hunger and brain activity. The research suggests that sucralose could trick the brain into feeling hungrier by triggering appetite-related activity in the hypothalamus without providing the expected calories.
Sucralose Activates Hunger Areas in the Brain
USC researchers found that sucralose, a commonly used calorie-free sweetener, activates the hypothalamus—the region of the brain responsible for regulating appetite and body weight. This activation is stronger than that caused by regular sugar. The study also noted that sucralose changes how the hypothalamus communicates with other brain areas related to motivation and sensory processing.
The findings, published in Nature Metabolism, highlight concerns about the long-term effects of calorie-free sweeteners on eating habits, particularly in people with obesity and children.
The Study: Testing the Effects of Sucralose
The study, led by Dr. Kathleen Alanna Page, director of the USC Diabetes and Obesity Research Institute, examined how sucralose affects brain activity, hormones, and hunger. Despite previous research linking artificial sweeteners to obesity, this study focused on direct tests with humans to measure the sweetener’s effect on hunger.
The team tested 75 participants, including men and women with varying weight statuses, in a randomized controlled study. Each participant consumed a beverage sweetened with sucralose, sugar, or water, and the researchers tracked brain activity, blood samples, and hunger levels. The results showed that consuming sucralose led to higher brain activity in the hypothalamus and increased feelings of hunger, particularly in people with obesity. In contrast, sugar did not have the same effect.
The Brain’s Reaction to Sweetness
Dr. Page explains that sucralose creates a “mismatch” in the brain’s expectations. The sweet taste suggests calorie intake, but sucralose delivers none, confusing the body’s hunger signals. This mismatch could lead to changes in cravings and eating behaviors over time.
“If the body expects a calorie due to the sweetness but doesn’t receive it, it could alter the brain’s response to cravings in the future,” Page said.
Study Results: Increased Hunger and Brain Connectivity
Participants in the study consumed 300 ml of a drink sweetened with either sucralose, sugar, or water. Researchers found that sucralose increased brain activity in the hypothalamus and heightened hunger sensations compared to both sugar and water. The effect was especially strong in people with obesity.
The study also used fMRI scans to examine brain connectivity. Sucralose consumption led to increased communication between the hypothalamus and other brain regions involved in motivation and sensory processing, such as the anterior cingulate cortex, which is important for decision-making.
Hormonal Impact: Sucralose vs. Sugar
The study revealed that consuming sugar increased blood levels of insulin and glucagon-like peptide 1 (GLP-1), hormones that help regulate appetite and signal fullness. However, sucralose had no such effect, meaning it did not trigger the body’s usual response to food intake, leaving hunger unaddressed.
Dr. Page pointed out that the difference in hormonal responses between sucralose and sugar was most pronounced in individuals with obesity, suggesting that sucralose may have a more significant impact on these individuals.
Gender Differences and Future Implications
The study also found notable gender differences in brain activity. Female participants showed more significant changes in brain responses compared to male participants, indicating that sucralose may affect men and women differently.
Looking ahead, the USC team is conducting follow-up research to examine the long-term effects of calorie-free sweeteners, particularly in children and adolescents, who consume more sugar substitutes than other age groups. The researchers are concerned about how sucralose might impact the developing brains of young people, who are already at higher risk for obesity.
“Children’s brains are especially vulnerable, and this could be a critical time to intervene before unhealthy eating behaviors take hold,” Page said.
Conclusion:
This new research casts doubt on the effectiveness of diet drinks and artificial sweeteners in managing hunger and weight. While sucralose provides a sweet taste without calories, it appears to interfere with the brain’s natural signals for hunger and fullness, especially in those with obesity. As the study progresses, scientists are exploring the long-term effects of these sweeteners, particularly on developing brains. The findings suggest that we may need to reconsider the impact of artificial sweeteners on our health, especially for vulnerable populations like children.
DOI: 10.1038/s42255-025-01227-8
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