A randomized crossover trial published in Nature Metabolism found that sucralose, the calorie-free sweetener in thousands of consumer products, increased blood flow to the brain’s hunger center and left participants feeling hungrier than those who drank sugar-sweetened beverages. The 75-person neuroimaging study adds to a growing body of evidence that artificial sweeteners do not simply pass through the body unnoticed but instead alter appetite regulation in ways that real sugar does not. Those findings arrive alongside a fresh European Food Safety Authority review and persistent questions about whether zero-calorie drinks actually help people eat less.
Sucralose Drives Hypothalamic Blood Flow and Hunger
The core finding comes from a randomized crossover trial conducted at the Keck School of Medicine at USC and published in Nature Metabolism. Seventy-five young adults each consumed a sucralose-sweetened drink, a sweetness-matched sucrose drink, and water on separate visits, then underwent MRI scanning. After the sucralose drink, hypothalamic blood flow rose significantly (P less than 0.018), and self-reported hunger jumped even more sharply (P less than 0.001). Sucrose produced no comparable spike in either measure. Because the hypothalamus acts as the brain’s primary thermostat for appetite, increased blood flow there after a zero-calorie drink suggests the brain is registering a mismatch between the sweet taste it detected and the energy it received.
That mismatch may explain a paradox familiar to anyone who has switched to diet soda and still felt hungry afterward. The trial, registered on ClinicalTrials.gov as “Brain Response to Sugar II” (NCT02945475), was designed as a crossover so each participant served as their own control, reducing the noise that comes from comparing different people. The direction of the effect was consistent: sucralose amplified hunger signals rather than suppressing them, directly challenging the premise that calorie-free sweeteners help reduce overall food intake. While the study was relatively small and short-term, its tightly controlled design and direct brain imaging give unusual insight into how the body actually responds to a common diet ingredient.
Earlier Brain Imaging Told a Similar Story
The Nature Metabolism results did not emerge in a vacuum. A 2019 fMRI study in Nutrition used a randomized, within-subject design to compare hypothalamus and ventral tegmental area responses after 16 healthy men ingested glucose, fructose, sucrose, sucralose, or water. In that work, available through PubMed, natural sugars produced a hypothalamic deactivation pattern, the kind of signal associated with satiety, while sucralose failed to trigger the same response. In practical terms, the brain recognized real sugar as fuel and dialed down its hunger alarm. The artificial sweetener left that alarm running, which aligns with the heightened hunger seen in the newer trial.
Separate fMRI work published in NeuroImage examined taste-processing pathways and found that sucrose activated key taste and reward regions, including the anterior insula, frontal operculum, striatum, and anterior cingulate, more strongly than sucralose. Sucrose, not sucralose, also engaged dopaminergic midbrain areas in proportion to how pleasant participants rated the taste. That distinction matters because dopamine-driven reward signals help the brain learn which foods are worth seeking out and when enough energy has been consumed. If artificial sweeteners deliver sweetness without triggering the full reward circuit, the brain may compensate by pushing a person toward calorie-dense foods later, a hypothesis that fits both the imaging data and the hunger reports from the larger crossover trial.
Regulators Accept Safety but Flag Limits
None of these brain-level findings have prompted regulators to pull sucralose from the market. The U.S. Food and Drug Administration sets the acceptable daily intake (ADI) for sucralose at 5 mg per kilogram of body weight per day, based primarily on toxicology studies that look for organ damage, cancer, or reproductive harm at high doses. The European Food Safety Authority, in a review dated February 17, 2026, confirmed its own ADI of 15 mg per kilogram and stated that current exposure remains below that threshold for currently authorized uses. At the same time, EFSA could not confirm safety for extending sucralose into additional food categories, a cautious note that signals regulators see open questions even within existing safety margins.
The gap between “safe at current levels” and “beneficial for health” is where most of the tension sits. Regulatory approval addresses acute toxicity and long-term carcinogenicity, not whether a sweetener quietly rewires appetite circuits over months or years of daily use. The brain imaging data do not show harm in the traditional toxicological sense, but they do show that the body responds to sucralose in ways its calorie-free label does not advertise. For consumers who choose diet beverages specifically to eat less, that distinction carries real weight, especially when considered alongside observational data linking high intake of non-sugar sweeteners with metabolic and cardiovascular risk.
WHO and Emerging Research Push Back on Weight-Loss Claims
The World Health Organization took a more direct stance in 2023, recommending against using non-sugar sweeteners for weight control. That guidance, summarized in a WHO news release, drew on a systematic review that found no long-term benefit for reducing body fat and flagged potential associations with type 2 diabetes, cardiovascular disease, and increased mortality. The full recommendation, detailed in the organization’s guideline document, is technically conditional, meaning the evidence was strong enough to justify caution but not definitive enough to rule out all possible benefits in every context. Still, the signal was clear: replacing sugar with artificial sweeteners does not appear to produce the lasting weight loss that millions of consumers expect.
Clinical and observational research has echoed that message. A randomized trial reported in Nutrition and accessible via its DOI record compared drinks sweetened with sucralose to sugar-sweetened beverages in adults with overweight and obesity. While artificial sweeteners reduced immediate calorie intake from beverages, the study found limited evidence that this translated into meaningful, sustained weight loss over time, in part because participants tended to compensate by eating more later. Longer-term cohort studies cited in the WHO review similarly linked high consumption of non-sugar sweeteners with higher, not lower, risks of weight gain and metabolic disease. Together with the brain-imaging work, these findings undercut the narrative that simply swapping sugar for sucralose is a reliable route to better health.
What the Evidence Means for Everyday Choices
For individuals trying to navigate supermarket shelves, the emerging picture is nuanced rather than absolute. Sucralose and other non-sugar sweeteners clearly reduce the immediate calorie load compared with sugar, which can be useful for people with diabetes or those who need to cut back on added sugars quickly. At the same time, neuroimaging studies show that the brain does not treat all sweetness equally: real sugar appears to signal “energy received” and dampen hunger, while sucralose delivers sweetness without the same satiety response and may even heighten appetite in some people. Observational data and WHO’s review suggest that, over years, this disconnect can blunt or even reverse the hoped-for weight-loss benefits.
That does not mean everyone must avoid sucralose entirely, but it does argue against viewing “diet” labels as a free pass. For many people, the more reliable strategy may be to gradually reduce overall sweetness (whether from sugar or artificial substitutes) so that less intensely sweet foods and drinks become satisfying again. Pairing any use of non-sugar sweeteners with attention to total calorie intake, fiber-rich foods, and protein can also help keep hunger in check. As regulators continue to review safety and researchers probe how the brain responds to different kinds of sweetness, the simplest takeaway may be this: sucralose is not an inert stand in for sugar, and relying on it alone is unlikely to solve the complex challenge of long-term weight control.
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*This article was researched with the help of AI, with human editors creating the final content.
