Why sucralose could make you hungrier instead of helping you lose weight

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.Mar 30 2025

A new study reveals how sucralose may backfire by boosting hunger-related brain activity—especially in women and those with obesity—challenging its role in weight management strategies.

Study: Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights. Image Credit: SabOlga / Shutterstock

In a recent study published in the journal Nature Metabolism, researchers investigated how acute consumption of sucralose influences brain activity related to appetite compared to sucrose and water across individuals with varying body weights.

Background

What if the sucralose-sweetened beverage you are sipping actually makes you hungrier? Obesity rates have risen dramatically over the last three decades, prompting millions to seek weight management solutions, often opting for beverages sweetened with non-caloric substitutes like sucralose.

While intended to reduce calorie intake, emerging evidence suggests these sweeteners may disrupt brain signals controlling hunger, paradoxically increasing appetite and food consumption. With conflicting results from previous studies, understanding precisely how sucralose impacts the brain’s hunger mechanisms is vital.

Clarifying this relationship could lead to healthier dietary choices, ultimately benefiting individuals and communities in their effective management of obesity and related health issues. Further research is necessary to confirm these effects over longer periods and to clarify how different individuals may uniquely respond to sucralose consumption.

About the study

A randomized crossover trial involving 75 healthy young adults, aged 18–35 years with varied body weights (healthy, overweight, obese), was conducted. Participants visited a research center three times, each separated by 2 days to 2 months. Randomly, they received one of three beverages: sucralose (a non-caloric sweetener), sucrose (table sugar), or water. Each drink was matched for sweetness (except water, which served as a non-sweet control). Magnetic Resonance Imaging (MRI) was used to measure brain blood flow, particularly in the hypothalamus, a key area controlling hunger, before and after drink consumption at intervals of 10 and 35 minutes.

Blood samples were drawn at these intervals to measure glucose, insulin, and glucagon-like peptide-1 (GLP-1), hormones associated with hunger and satiety. Participants rated their hunger on a scale at various intervals during visits. Brain connectivity patterns between the hypothalamus and regions involved in appetite, reward, and motivation were analyzed via functional MRI. Adjustments were made statistically for age, sex, race/ethnicity, and body mass index (BMI) to ensure accuracy and reliability.

Study results

Sucralose significantly increased hypothalamic blood flow compared to sucrose and water, suggesting that it may increase hunger signals in the brain. Participants reported feeling notably hungrier after drinking sucralose compared to sugar, but not when compared with water (P = 0.99), despite increased hypothalamic activity. Sugar consumption significantly raised blood glucose levels, correlating with decreased hypothalamic activity and reduced hunger, suggesting normal calorie-driven hunger suppression.

Participants with healthy weights exhibited increased hypothalamic activity after sucralose consumption compared to sucrose. In contrast, individuals with obesity exhibited increased hypothalamic activity after consuming sucralose compared to water, but not compared to sucrose.

Across the full sample, however, sucralose increased hypothalamic activity compared to both sucrose and water (P < 0.018 and P < 0.019, respectively). Responses in overweight participants fell between these extremes, with no statistically significant differences.

Interestingly, women displayed significantly greater lateral hypothalamic responses to sucralose than men, supporting previous findings that women generally exhibit heightened brain reactions to food cues, which may influence their eating behaviors and vulnerability to dietary sweeteners.

Sucralose increased functional connections between the hypothalamus and brain areas responsible for motivation and reward processing, notably the anterior cingulate cortex. This enhanced connectivity may help explain why consuming diet beverages might contribute to intensified cravings and food-seeking behaviors. These connectivity differences varied significantly across weight groups, suggesting that personalized neural reactions may depend on one's body weight.

Furthermore, glucose elevations after sugar intake were inversely linked to hypothalamic activity, especially in the medial hypothalamus. This relationship highlights the significance of normal glucose signaling in regulating hunger. However, participants with obesity showed weaker responses, hinting at disrupted glucose signaling pathways, possibly exacerbating hunger and overeating behaviors.

Although hormonal responses, such as insulin and GLP-1, were notably higher with sugar intake compared to sucralose, these hormonal changes did not correlate with changes in hypothalamic blood flow, suggesting complex interactions between these physiological factors in appetite control.

Conclusions

To summarize, this research reveals that sucralose uniquely activates brain regions responsible for hunger without providing caloric satisfaction, which may drive increased food intake. Differences based on body weight and sex highlight the need for personalized dietary guidance regarding non-caloric sweeteners. These sweeteners may unintentionally disrupt appetite regulation, complicating weight management efforts.

Considering their widespread use globally, understanding the long-term effects of non-caloric sweeteners, such as sucralose, is crucial. Future studies are crucial for developing clear, evidence-based nutritional recommendations, ultimately aiming to enhance public health and combat rising obesity rates more effectively.