Brain scans reveal how artificial sweeteners affect our reward circuits differently than sugar

An experimental study compared changes in brain activity after ingestion of water and different types of flavored waters. Results showed that cerebral blood flow in the hypothalamus (a brain region that controls homeostatic processes like hunger and thirst) was not differentially affected by any of the drinks. However, the ventral tegmental area (a midbrain region involved in reward and motivation) showed lower changes in cerebral blood flow after sucrose than after water, sucralose, or monk fruit drink ingestion. The paper was published in The American Journal of Clinical Nutrition.

As obesity rates have risen worldwide, reducing excessive energy intake has become an important goal for both individuals and public health. One widely used strategy is to replace sugar with low- or no-calorie sweeteners, particularly in beverages, where added sugars can contribute substantially to daily calorie intake. Although concerns are often raised that exposure to sweetness might increase cravings for sweet foods, current evidence does not consistently support this idea.

At the same time, low- and no-calorie sweeteners should not necessarily be viewed as a single, uniform group. Different sweeteners can vary in taste, metabolic effects, effects on the gut microbiome, and the physiological responses they produce after consumption. Sugars themselves also differ in how they are processed by the body and in their effects on blood glucose and other metabolic processes.

Because the brain plays a central role in hunger, satiety, reward, and energy regulation, researchers are increasingly interested in how different sweeteners influence brain activity after consumption. Brain-imaging research suggests that caloric sugars and non-caloric sweeteners may sometimes produce different responses in regions involved in appetite regulation, including the hypothalamus, although findings remain inconsistent.

Study author Paul AM Smeets and his colleagues conducted a study in which they examined changes in brain activity and physiological markers after the ingestion of flavored waters sweetened with the sugar sucrose or various low-no-calorie sweeteners. They hypothesized that sugar sucrose would elicit decreased cerebral blood flow (indicating decreased neural activity) in brain areas related to food intake regulation and reward 30 minutes after ingestion. They expected that low- or no-calorie sweeteners and water would not produce such effects due to their low or absent energy content.

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Study participants were 30 healthy individuals. Fifteen of them were men. Their average age was 23 years. They completed six treatment sessions between February 2023 and March 2024.

The treatment consisted of ingestion of 500 milliliters of either water or one of five equally sweet, lemon-lime flavored waters sweetened with sucrose (25 grams, 97 kcal) or sucralose, stevia extract, monk fruit extract, or allulose + stevia extract.

Sucralose is a high-intensity artificial sweetener made from modified sucrose that provides sweetness with virtually no calories. Stevia extract is a plant-derived sweetener obtained from Stevia rebaudiana and contains sweet compounds called steviol glycosides. Monk fruit extract is a natural high-intensity sweetener derived from Siraitia grosvenorii fruit. Allulose is a rare low-calorie sugar with properties similar to ordinary sugar. Stevia is mixed with allulose to increase sweetness while keeping calorie content low. These sweeteners add little or no calories to a drink.

At the start of the treatment procedure, participants completed magnetic resonance imaging scans of their brains and of their stomachs. They also answered questions about appetite and well-being verbally. After this, they drank the drink assigned to them on the occasion. This was followed by two more scans of their brains and of their stomachs at different times up to 45 minutes after drinking.

Participants gave blood samples at the start and five more times up to an hour after drinking their assigned beverage (except on the day they received water). After the first sip, participants rated the tastiness and sweetness of the drink they consumed. All participants consumed their drinks within five minutes. Sixty minutes after drinking, after all the procedures were completed, participants were offered a takeaway breakfast.

Results showed that all sweet drinks were liked equally, except monk fruit, which was liked modestly less than the sucrose-sweetened drink. All sweetened drinks except the one with monk fruit were liked more than water. All sweetened drinks were perceived as sweeter than water. The monk fruit-sweetened drink and the drink sweetened with allulose+stevia were rated modestly less sweet than the sucrose-sweetened drink.

Cerebral blood flow in the hypothalamus was similarly affected by all sweet drinks. Cerebral blood flow is an indirect indicator of activity in a particular region of the brain, with higher cerebral blood flow generally suggesting higher neural activity.

In the ventral tegmental area, the change in the cerebral blood flow was lower after sucrose than after water, sucralose, and monk fruit drink 30 minutes after ingestion. This suggests that neural activity in that region of the brain was lower after ingesting the sucrose-sweetened drink than after water, and drinks sweetened with sucralose and monk fruit extract.

Exploratory analyses showed increased cerebral blood flow (and thus increased neural activity) after consumption of the allulose+stevia-sweetened drink in the amygdala region of the brain and after the stevia-sweetened drink in the putamen region of the brain compared to the sucrose-sweetened drink. Despite its low energy content, the allulose+stevia-sweetened drink delayed gastric emptying (the speed at which food leaves the stomach) similar to the sucrose-sweetened drink, whereas only the sucrose-sweetened drink increased glucose and insulin concentrations.

“Although flavored waters with LNCS [low or no calorie sweeteners] mostly elicit similar neural and gastrointestinal responses as water, they have some distinct effects on the brain compared with 25 g of sucrose, particularly in reward-related brain areas,” study authors concluded.

The study contributes to the scientific knowledge about brain reactions to sweetened beverages. However, it should be noted that the study was conducted on a very small group of participants, which may have made some differences in brain reactions undetectable using usual statistical procedures. Also, participants were young people and results may not generalize to other age groups.

The paper, “Brain and physiological responses to flavored waters with different sweeteners: a randomized crossover study in healthy young adults,” was authored by Paul AM Smeets, Ralf Veit, Els Oosterink, Saskia Meijboom, Davide Risso, Hubert Preissl, and Stephanie Kullmann.