Not all zero-calorie sugar substitutes are as sweet as they might seem.
New research suggests that sucralose — one of the most popular artificial sweeteners on the market — messes with a brain region responsible for controlling hunger, particularly in people with obesity.
The finding raises new questions about whether sugar alternatives, used by around 40% of Americans to indulge their sweet tooth without the calories, are an effective tool for weight management.
The sugar struggle
The American Heart Association recommends that men consume no more than 9 teaspoons and women no more than 6 teaspoons of added sugar per day. Yet, the average American is gulping down a staggering 17 teaspoons daily.
Excessive sugar intake is a key contributor to weight gain, primarily due to the extra calories it provides. With 40% of US adults and nearly 1 in 5 children and adolescents considered obese, it’s no surprise that sugar substitutes have surged in popularity.
Enter sucralose. Commonly marketed as Splenda, this ingredient is frequently found in diet sodas, baked goods, and chewing gum. It’s 600 times sweeter than sugar and calorie-free, but it may not be the miracle product it’s cracked up to be.
What happens to your brain on sucralose?
Earlier studies have hinted at a potential link between calorie-free sweeteners and obesity, but they haven’t fully explained how these substances affect hunger in humans.
To find out, researchers at the University of Southern California studied how 75 participants of varying body weights responded after consuming water, a sucralose-sweetened drink, or a sugar-sweetened drink on three separate occasions.
During each session, the researchers closely monitored participants’ brain activity, blood levels, and hunger before and after drinking.
Compared to sugar, the team found that consuming sucralose triggered heightened brain activity in the hypothalamus, the area responsible for regulating appetite, and led to increased hunger — particularly in people with obesity.
The researchers also discovered that sucralose enhanced connectivity between the hypothalamus and other brain regions linked to motivation and decision-making.
The study highlights how sucralose “confuses the brain” by providing a sweet taste without the expected caloric energy, explained Dr. Kathleen Alanna Page, the study’s corresponding author and director of the USC Diabetes and Obesity Research Institute.
She cautioned that this “mismatch” could lead to long-term shifts in cravings and eating behavior.
“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,” she said.
As expected, Page and her team found that consuming sugar spiked blood sugar levels and triggered the release of hormones like insulin and glucagon-like peptide 1 (GLP-1), which help regulate hunger.
However, drinking sucralose had zero impact on those hormones.
“The body uses these hormones to tell the brain you’ve consumed calories, in order to decrease hunger,” Page said. “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 also found that female participants experienced greater changes in brain activity compared to their male counterparts, suggesting sucralose might have a different effect on the sexes.
The next frontier
The study raises key questions about whether the observed changes in brain and hormone activity have long-term effects. The researchers are calling for further studies that track body weight and eating habits to better understand the potential link.
In the meantime, Page and her colleagues have launched a follow-up study to explore how calorie-free sweeteners affect the developing brains of children and adolescents, a group that consumes more sugar and sugar substitutes than any other.
“Are these substances leading to changes in the developing brains of children who are at risk for obesity?” Page asked. “The brain is vulnerable during this time, so it could be a critical opportunity to intervene.”
Sugar vs. artificial sweeteners
Despite the allure of zero- or low-calorie options, there are growing concerns about whether artificial sweeteners are truly effective for weight loss.
The American Heart Association and the American Diabetes Association support the use of these sweeteners as sugar substitutes to combat obesity, metabolic syndrome, and diabetes — all risk factors for heart disease.
But in 2023, the World Health Organization cautioned against the use of non-sugar sweeteners for weight management, following a review that found no long-term weight loss benefits for either adults or children.
While added sugars carry their own set of health risks, some research suggests that sugar substitutes may come with their own set of downsides.
Studies have shown that sucralose can negatively impact gut health, damage DNA, disrupt the liver’s detoxification process, and even potentially increase the risk of diabetes.
That said, the International Sweeteners Association, the main trade group representing the artificial sweetener industry, argues that an extensive body of research has confirmed the safety of low- or no-calorie sweeteners for consumers.
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