New study links sucralose (Splenda) to hypothalamus changes compared with sucrose

Nothing is truly cost-free - not even a sugar-free drink.

Researchers have now associated the artificial sweetener sucralose (sold as Splenda) with another possible health drawback. This time the effect is not centred in the gut; it appears to involve the brain.

What the sucralose (Splenda) trial found in the hypothalamus

In a randomised crossover trial, 75 adults who drank a beverage containing sucralose showed increased blood flow to the hypothalamus - a brain region that helps regulate appetite and cravings.

When those same participants instead drank a drink containing sucrose (that is, table sugar), the pattern looked different. Their peripheral glucose levels rose, and this was linked with reduced blood flow to the hypothalamus - an effect consistent with dampening hunger.

Two hours after consuming sucrose, participants reported significantly lower hunger than they did after drinking sucralose.

Taken together - and backed by early rodent research - the results indicate that non-caloric sweeteners may not be especially helpful for long-term weight loss or for reducing sugar cravings. The findings also suggest these sweeteners can alter how the hypothalamus communicates with other brain regions.

Sucralose is 600 times sweeter than sucrose but contains zero calories. The researchers say this may create "a mismatch between the expectation of caloric intake and the absence of actual energy".

"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," warns a supervisor of the study, endocrinologist Kathleen Alanna Page from the University of Southern California.

How the study was carried out

Page and colleagues emphasise the importance of further work on the long-term health effects of Splenda and similar sweeteners - particularly given that as many as 40 percent of US adults regularly consume these sugar substitutes.

The trial enrolled 75 participants aged 18 to 35. Each person completed three interventions, with blood tests and brain scans performed before and after each session.

On one visit, participants drank a beverage containing sucralose. On another, they consumed a beverage containing sucrose. On a third, they drank a glass of water. To prevent people from identifying what they were receiving, all drinks had an unsweetened cherry flavour. Each participant acted as their own control.

The order of the drinks was randomised for each individual, and the interval between sessions ranged from two days to two months.

Hormones, glucose signals, and why the results matter

In contrast to real sugar, sucralose did not trigger a rise in peripheral glucose levels, nor did it produce spikes in hormones such as insulin and glucagon-like peptide 1 (GLP-1), which help regulate blood sugar.

"The body uses these hormones to tell the brain you've consumed calories, in order to decrease hunger," explains 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."

This points to a close link between the body’s metabolic signals and brain activity. Earlier studies, for example, suggest that when sucralose interacts with gut microbes it can weaken the body’s response to glucose - and it is possible this also contributes to the distinctive hypothalamic response observed in the new work.

Splenda was once considered biologically inert. More recent research, however, has reported worrying indications that this widely used sugar substitute - common in diet drinks and chewing gum - is associated with DNA damage, impairments in glucose tolerance, and changes to the gut microbiome.

Two years after the World Health Organization issued a health warning about sucralose and its possible metabolic and inflammatory effects, these findings add another reason to be cautious about consuming the sweetener indiscriminately.

Page and her team are now running a follow-up study to examine how sucralose affects the brains of children and adolescents in particular.

"Are these substances leading to changes in the developing brains of children who are at risk for obesity?" asks Page.

"The brain is vulnerable during this time, so it could be a critical opportunity to intervene."

The study was published in Nature Metabolism.