Artificial sweeteners like sucralose are marketed as healthier alternatives to sugar, but they may send mixed signals to the brain. A recent study found that sucralose increased hunger and altered activity in the part of the brain that regulates appetite, with effects differing by body weight.

Researchers asked 75 young adults—some with a healthy weight and some with overweight or obesity—to drink a beverage sweetened with either sucralose (often marketed as Splenda), sucrose (table sugar), or plain water on three separate occasions. Afterward, the researchers measured the participants' blood glucose levels, collected their self-reported hunger ratings, and conducted brain scans to examine activity and connectivity in key regions involved in appetite control.

Compared to sugar, sucralose increased blood flow to the hypothalamus and promoted stronger feelings of hunger. Sucralose also heightened hypothalamic activity more than water but didn’t influence hunger. Only sugar elevated blood glucose levels, an increase linked to reduced activity in the hunger-regulating regions of the brain.

Interestingly, the brain’s response to sucralose differed based on body weight: In people with a healthy weight, sucralose enhanced connections between the hypothalamus and areas involved in attention and decision-making. In those with overweight, sucralose diminished connections to brain regions that process bodily sensations. And those with obesity exhibited little to no change in these neural connections. Compared to water, both sweeteners elicited distinct patterns of brain activity depending on weight status.

These findings suggest that sucralose interferes with the brain’s normal appetite-regulating signals by mimicking sweetness without delivering the expected rise in blood sugar. This mismatch appears to increase hunger and alter brain connectivity in ways that vary depending on body weight. Artificial sweeteners also affect the gut microbiome. Learn more in this clip featuring Dr. Eran Elinav.