New trial links sucralose (Splenda) to hypothalamus blood flow and hunger

Nothing in life is truly free - not even a sugar-free drink.

Researchers have now connected the artificial sweetener sucralose (sold as Splenda) with another possible health drawback. This time, the effect does not appear to be centred in the gut; it shows up in the brain.

What the trial found about sucralose and the hypothalamus

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

When those same individuals instead consumed a drink sweetened with sucrose (ordinary table sugar), the pattern went the other way. Their peripheral glucose levels rose, and this increase was associated with reduced blood flow to the hypothalamus, consistent with a hunger-dampening effect.

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

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

How the randomised crossover study was run

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

On one visit, participants drank a sucralose-sweetened beverage. On another, they drank a sucrose-sweetened beverage. On a third, they drank a glass of water. All three drinks were given an unsweetened cherry flavour so participants could not tell which one they were receiving, and each participant acted as their own control.

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

Unlike sucrose, sucralose did not trigger a rise in peripheral glucose, nor did it prompt increases 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."

Why Splenda’s sweetness may confuse appetite signals

Sucralose is 600 times sweeter than sucrose while containing zero calories. The authors suggest this can 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.

The results also point to a tight relationship between metabolic signals in the body and activity in the brain. Previous research has found that when sucralose interacts with gut microbes, it can weaken the body’s response to glucose. It is possible this process contributes to the distinctive hypothalamic response observed in the new study.

Wider concerns and next steps

Page and her colleagues argue that long-term health effects of Splenda and similar sweeteners need careful study, particularly given that as many as 40 per cent of American adults are said to consume these sugar substitutes regularly.

At one point, Splenda was considered biologically inert, but more recent research has reported worrying indications linking this widely used sweetener - common in diet drinks and chewing gum - with DNA damage, reduced 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 impacts, there is now another reason to be cautious about consuming the sweetener willy-nilly.

Page’s team is 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.