Are Artificial Sweeteners Fueling Hunger Instead of Fighting It?

Could the very products designed to help with weight management be making the problem worse?

A new study from the Keck School of Medicine at the University of Southern California (USC), published in Nature Metabolism, has found that sucralose – a widely used artificial sweetener – alters brain activity linked to hunger and appetite regulation.

The promise vs the reality of artificial sweeteners

​Artificial sweeteners have become a staple in the diets of many individuals aiming to manage their weight. Approximately 40% of Americans regularly consume these sugar substitutes, attracted by the promise of indulging in sweetness without the accompanying calories.

However, despite the widespread adoption of artificial sweeteners, obesity rates continue to climb, prompting researchers to question the efficacy of these sugar alternatives. This incongruity has led to what some term the “artificial sweetener paradox,” where substances designed to combat weight gain might, paradoxically, contribute to it.

Observational data has suggested that non-nutritive sweeteners may promote weight gain through increased cravings and altered reward responses. Conversely, interventional studies have indicated that substituting artificial sweeteners for sugar-sweetened beverages can reduce caloric intake and moderate weight loss.

Beyond their metabolic effects, artificial sweeteners may also be influencing the brain’s response to food and hunger. Some research suggests that the mismatch between sweetness and caloric content can disrupt appetite regulation, leading to changes in cravings and eating behaviors. Yet, studies directly examining how artificial sweeteners affect brain activity remain scarce.

“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,” said corresponding author Dr. Kathleen Alanna Page, co-chief of the Division of Endocrinology & Diabetes, director of the Diabetes and Obesity Research Institute at the Keck School of Medicine of USC.

With conflicting evidence, one question remains: Could sucralose and other artificial sweeteners be driving overeating rather than preventing it?

How sucralose alters hunger and brain activity

Page and colleagues conducted a controlled, randomized design study to investigate how consuming sucralose impacts brain activity, hormone levels and hunger responses compared to sugar and water.

The team enrolled 75 participants, split evenly by sex and weight status (healthy weight, overweight and obese). On separate visits, they consumed either water, a sugar-sweetened drink or a sucralose-sweetened drink. Researchers then collected functional MRI (fMRI) brain scans, blood samples and hunger ratings before and after consumption to track physiological and neurological responses over time.

Page and the team found sucralose increased activity in the hypothalamus, a key brain region responsible for regulating appetite. This effect was particularly pronounced in individuals with obesity, raising concerns that sucralose may be exacerbating, rather than alleviating, issues with weight regulation.

“We expected sucralose to affect the hypothalamus differently than sugar, but we were surprised by how strongly the hypothalamus responded to sucralose in individuals with obesity,” Page told Technology Networks.

“These differences may help explain why previous research on non-caloric sweeteners has produced mixed results. Different groups may be responding differently at a brain level,” she added.

Unlike sugar, sucralose did not stimulate the release of key satiety hormones, including glucagon-like peptide-1 (GLP-1), which signals fullness to the brain. Without this hormonal feedback, the brain remains in a state of craving, potentially leading to increased hunger and food intake.

“The body uses these hormones to tell the brain you’ve consumed calories, in order to decrease hunger – sucralose did not have that effect. The differences in hormone responses to sucralose compared to sugar were even more pronounced in participants with obesity,” said Page.

Blood glucose and insulin levels remained largely unaffected by sucralose, suggesting that its impact on hunger and cravings is driven primarily by brain and hormonal changes rather than immediate metabolic effects.

Further analysis using fMRI scans revealed that sucralose also altered the hypothalamus’s communication with other brain regions involved in motivation and sensory processing, including the anterior cingulate cortex, a region linked to decision-making. These changes in neural connectivity suggest that sucralose consumption could influence long-term eating behavior, potentially increasing cravings for high-calorie foods. 

“The results align with prospective cohort studies showing that non-caloric sweeter consumption is associated with weight gain in some individuals, possibly due to altered brain signaling around hunger and satiety,” Page told us.

Female participants also exhibited greater hypothalamic activity changes than males, suggesting that sucralose’s effects on appetite and cravings may vary by sex.

“While the mechanism is not yet clear, our findings suggest that females may be more sensitive to the mismatch between the brain’s expectation of calories after tasting sweetness and the lack of receipt of calories,” said Page.

Although the study measured hunger ratings, it did not track whether participants consumed more food later in the day after sucralose intake. Changes in brain activity and hormone responses may suggest potential for increased eating but actual food consumption was not measured.

Rethinking our approach to “diet” foods

While sucralose and other non-nutritive sweeteners are marketed as a way to reduce sugar intake and lower calorie consumption, emerging research suggests they may have unintended consequences, particularly for those already struggling with weight.

Frequent consumption of sucralose appears to disrupt normal appetite regulation by increasing hunger signals in the brain without providing the expected energy. Over time, this could lead to heightened cravings, altered eating behavior and weight gain instead of loss.

“We are interested in learning how chronic sucralose consumption may affect brain pathways and eating behavior in the long term,” said Page.

Currently, organizations such as the American Heart Association and the American Diabetes Association cautiously endorse artificial sweeteners as a sugar substitute but acknowledge the need for more research. However, in 2023, the World Health Organization released guidelines advising against the use of non-sugar sweeteners for weight control, citing a lack of long-term benefits and potential risks for metabolic health.

Another area of interest is how artificial sweeteners affect children and adolescents. Since early-life dietary habits shape long-term health outcomes, researchers are now turning their attention to how these substances influence the developing brain.

“High intake of added sweeteners during early life could potentially alter the development of neural circuits involved in appetite regulation and reward processing, key systems that influence eating behavior,” said Page. “We plan to evaluate this in our longitudinal studies where we are following children from childhood through adolescence.”

With children being the highest consumers of artificial sweeteners, understanding their long-term impact is vital. Page and her colleagues at USC are launching a new study to investigate whether non-nutritive sweeteners affect brain development in ways that could increase the risk of obesity later in life.

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

As researchers continue to investigate the long-term effects of artificial sweeteners on brain function and metabolism, it’s clear that more studies are needed to determine whether these sugar substitutes truly help.

Reference: Chakravartti SP, Jann K, Veit R, et al. Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights. Nat Metab. 2025;7(3):574-585. doi: 10.1038/s42255-025-01227-8

About the interviewee:

Dr. Kathleen Page is an associate professor of medicine and pediatrics, co-chief of the Division of Endocrinology & Diabetes and director of the Diabetes and Obesity Research Institute at the Keck School of Medicine of the University of Southern California (USC). Page earned her Bachelor of Science and medical degree at USC and completed a residency in internal medicine and a fellowship in endocrinology at the Yale University School of Medicine followed by a post-doctoral fellowship at Yale University in neuroimaging in science. She joined the faculty at the Keck School of Medicine of USC in 2009. Her current research program has three major components: (i) brain and endocrine regulation of appetite and feeding behavior; (ii) brain and metabolic pathways involved in the development of obesity and diabetes in children; (iii) effects of early-life exposure to diabetes on neurocognitive development.