Diet Drinks Can Trick Your Brain and Increase Your Hunger

Sucralose, a calorie-free sweetener, may increase hunger because it tricks the brain into tasting sweet without providing energy. One study used MRI to show that, unlike sugar, sucralose activates the hypothalamus, a region that regulates appetite, more and strengthens connections with areas linked to motivation to eat. This suggests that calorie-free sweeteners may influence appetite differently than regular sugar.

Sucralose is a widely used sweetener as an alternative to sugar because it provides a sweet taste without adding calories to the diet. Many people turn to calorie-free sweeteners to reduce their sugar intake and control their weight. However, some studies suggest that these sweeteners may stimulate appetite rather than reduce it.

This may be because the sweet taste activates taste sensors in the mouth, but unlike regular sugar (sucrose), sucralose does not trigger the same metabolic signals in the body that would normally help regulate hunger.

To investigate this effect, researchers at the University of Southern California, USA, conducted a randomized, crossover clinical trial with 75 young adults, including individuals with healthy weight, overweight and obesity.

In the study, participants consumed one of three beverages: one containing sucralose, another containing sucrose (table sugar) in an equivalent amount to achieve the same level of sweetness, or simply water. After consumption, scientists assessed how each beverage affected the participants’ brain and feelings of hunger.

The main technique used in this study to measure the effect of sucralose on the brain was functional magnetic resonance imaging (fMRI). fMRI detects changes in cerebral blood flow, allowing researchers to observe which areas of the brain are most active after consumption of the beverages (sucralose, sucrose or water).

An increase in blood flow in the hypothalamus indicates greater neuronal activation in this region, suggesting that the sweetener affected the mechanisms that regulate appetite.

The hypothalamus is a region of the brain that is essential for regulating hunger and energy balance. It receives and processes signals from the body, such as blood glucose levels, hormones (such as leptin and ghrelin), and neural signals from the digestive system.

When we eat food, these signals help the hypothalamus determine whether we should continue eating or whether we are full. In addition, this region controls the release of neurotransmitters that influence appetite and motivation to seek food.

Changes in these mechanisms, such as those observed when consuming non-caloric sweeteners, can impact the perception of hunger and eating behavior. In addition to measuring the isolated activity of the hypothalamus, the researchers analyzed how this region communicated with other areas of the brain involved in motivation and somatosensory processing.

This was done through a functional connectivity analysis, which identifies patterns of interaction between different brain regions while the participant is at rest or performing a task.

In addition to fMRI, the study also included subjective assessments of hunger (via questionnaires administered to participants) and measurements of blood glucose levels to correlate metabolic effects with brain activity.

The results showed that sucralose intake led to an increase in blood flow to the hypothalamus, a region of the brain essential for regulating appetite and metabolism. This effect was significant when compared to sucrose intake and was also observed when compared to water intake. In addition, participants who consumed sucralose reported feeling hungrier compared to those who consumed sucrose.

Sucrose, on the other hand, raised blood glucose levels, which was associated with a reduction in blood flow to the hypothalamus. This suggests that sugar activates the body's natural mechanisms that help suppress hunger. Sucralose, on the other hand, does not provoke this inhibitory response because it does not increase glucose levels in the same way.

Another important finding was that sucralose consumption increased functional connectivity between the hypothalamus and other brain areas responsible for motivation and sensory processing. This suggests that the sweetener may influence neural circuits involved in taste perception and food seeking, which may contribute to increased hunger and food cravings.

In summary, these results suggest that non-caloric sweeteners such as sucralose may directly impact brain mechanisms that regulate appetite. This raises questions about the use of these sweeteners as a weight control strategy, since, paradoxically, they may increase hunger and lead to overeating in the long term.

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Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights

Sandhya P. Chakravartti, Kay Jann, Ralf Veit, Hanyang Liu, Alexandra G. Yunker, Brendan Angelo, John R. Monterosso, Anny H. Xiang, Stephanie Kullmann and Kathleen A. Page

Nature Metabolism, volume 7,  pages 574–585 (2025)

DOI: 10.1038/s42255-025-01227-8

Abstract: 

Sucralose, a widely used non-caloric sweetener, provides sweet taste without calories. Some studies suggest that non-caloric sweeteners stimulate appetite, possibly owing to the delivery of a sweet taste without the post-ingestive metabolic signals that normally communicate with the hypothalamus to suppress hunger. In a randomized crossover trial (ClinicalTrials.gov identifier: NCT02945475), 75 young adults (healthy weight, overweight or with obesity) consumed a drink containing sucralose, sweetness-matched sucrose or water. We show that acute consumption of sucralose versus sucrose stimulates hypothalamic blood flow (P < 0.018) and greater hunger responses (P < 0.001). Sucralose versus water also increases hypothalamic blood flow (P < 0.019) but produces no difference in hunger ratings. Sucrose, but not sucralose, increases peripheral glucose levels, which are associated with reductions in medial hypothalamic blood flow (P < 0.007). Sucralose, compared to sucrose and water, results in increased functional connections between the hypothalamus and brain regions involved in motivation and somatosensory processing. These findings suggest that non-caloric sweeteners could affect key mechanisms in the hypothalamus responsible for appetite regulation.