New research cautions that non-calorie sweetener affects brain appetite regulation

A randomized crossover trial reveals that consuming sucralose, a common non-calorie sweetener, instead of sugar increases activity in the hypothalamus brain region, which regulates appetite and hunger cues. The sweetener also changes how the hypothalamus communicates with other brain parts, such as areas involved in motivation.

Researchers at the University of Southern California (USC), US, tested how 75 participants responded after consuming water, a drink with sucralose, or a drink sweetened with regular sugar (sucrose). Compared to a sugar-sweetened beverage, drinking sucralose increased feelings of hunger. 

The use of low- or no-calorie sweeteners such as sucralose is growing as a way to reduce calories or sugar consumption. 

“Are these substances helpful for regulating body weight? What happens in the body and brain when we consume them, and do the effects differ from one person to the next?” questions the study’s corresponding author, Kathleen Alanna Page, director of the USC Diabetes and Obesity Research Institute and co-chief of the Division of Endocrinology and Diabetes at the Keck School of Medicine of USC.

She adds that the findings show how sucralose “confuses the brain” by providing a sweet taste without the expected calorie energy. “If your body is expecting a calorie because of the sweetness but doesn’t get it, that could change how the brain is primed to crave those substances over time.” 

Increasing brain activity

The study published in Nature Metabolism included 75 male and female participants, evenly split into three weight categories: healthy weight, overweight, or obese. Researchers collected baseline brain scans and blood samples. 

On three separate visits, each individual drank a beverage with sucralose, sugar, or just water to analyze differences within and between participants. 

Before and after each drink consumption, researchers collected functional magnetic resonance imaging (fMRI) brain scans, blood samples, and hunger ratings. They conducted follow-up tests several times during two hours after drinking a 300 ml beverage. 

Compared to drinking a sugar-sweetened drink, sucralose increased hunger and activity in the hypothalamus, especially in people with obesity.The team found that sucralose increased hunger and activity in the hypothalamus, especially in people with obesity. Compared to drinking water alone, sucralose increased activity in the hypothalamus but did not change feelings of hunger. 

Impact on appetite

Unlike sugar, the sweetener did not increase blood levels of hormones that create a feeling of fullness. 

Sugar consumption also increased blood sugar levels and regulating hormones, such as insulin and GLP-1. Sucralose did not affect those hormones. 

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

The researchers studied functional connectivity in the participants through fMRI scans. They note that consuming sucralose led to increased connectivity between the hypothalamus and brain areas involved in motivation, sensory processing, and decision-making. 

Page says these findings suggest sucralose could impact cravings or eating behavior. 

Follow-up research

The researchers have started a follow-up study exploring how non-calorie sweeteners could affect the brains of children and adolescents. They note that this population consumes more sugar and sugar substitutes than any other age group. 

People may use low- or no-calorie sweeteners to lower their calorie or sugar consumption.“Are these substances leading to changes in the developing brains of children at risk for obesity? The brain is vulnerable during this time, so it could be a critical opportunity to intervene,” comments Page.

In addition, the authors say that longitudinal studies that measure changes in body weight and eating behavior are crucial to clarify the long-term effects of observed changes in brain and hormone activity. 

Moreover, the researchers observed differences by sex, with female participants showing more significant brain activity changes than male participants. 

In research on other sweeteners, there is an ongoing discussion on the health benefits and safety of aspartame. Last month, experts contested findings linking the no-calorie sweetener to heart health risks, saying there were insufficient results. 

Meanwhile, other studies have pointed to alternative sugar substitutes. For example, research says that honey matches sugar’s taste but contains fewer calories, while another finds maple syrup improves multiple cardiometabolic risk factors compared to sugar.