June 16, 2026, 6:51 pm | Read time: 6 minutes

2015 Study Showed Effect on Humans

In 2015, researchers at the University of Southern California examined how fructose and glucose directly affect humans. Twenty-four healthy adults drank either a fructose solution or a glucose solution (75 grams in 300 milliliters of cherry-flavored water) after a 12-hour fasting period. Their brain activity was then measured via MRI while they viewed images of high-calorie foods. Participants also reported how hungry they felt and made choices between an immediate food reward and a later monetary payment.¹

The result: After consuming fructose, participants felt hungrier and had more appetite than after glucose. At the same time, reward centers in the brain responded more strongly to images of food. This effect was also evident in behavior: After fructose, participants were more willing to forgo a later monetary reward to eat immediately.

A possible reason lies in the different hormonal responses. Glucose led to a significantly stronger increase in the hormone insulin, which normally signals the brain that the body has received enough energy. Fructose, on the other hand, affected other signaling pathways between the gut and the brain. The current study was able to clarify how these work in more detail.

How the New Study Was Conducted

Fructose and glucose are among the most commonly consumed types of sugar. Although both provide the same number of calories, they apparently affect metabolism and eating behavior differently. Researchers at the Monell Chemical Senses Center in Philadelphia wanted to find out in a mouse study whether the brain processes the two types of sugar differently.²

The focus was on so-called AgRP neurons in the hypothalamus–nerve cells that play an important role in hunger and food intake. Mice received fructose or glucose in identical calorie amounts. At the same time, researchers measured the activity of these hunger neurons and examined the effects on satiety, food intake, and food preferences. They also analyzed signaling pathways between the gut and the brain, including the vagus nerve.

Fructose Sends Different Signals Than Glucose

The central finding: Fructose inhibited the AgRP hunger neurons significantly less than the same calorie amount of glucose. The nerve cells responded not only to the calorie amount but also to the type of sugar consumed.

The authors see this as the key insight of their work. “Many people actually focus primarily on calorie intake. At the same time, it is increasingly recognized that not only the amount of calories but also their type is important. Our study goes a step further and shows that even different simple sugars like fructose and glucose can have very different effects on communication between the gut and the brain,” explains Dr. Amber Alhadeff, one of the lead authors of the mouse study.

Nevertheless, the mice did not eat more after fructose than after glucose in the short term. Researchers suspect that fructose stretches the gut more, triggering an additional satiety signal.

However, differences were observed in the animals’ preferences. They later preferred flavors associated with a stronger inhibition of hunger neurons. Accordingly, the choice more often fell on the glucose-associated flavor.

Researchers also identified a specific signaling pathway between the gut and the brain. Fructose increased the concentration of the gut hormone PYY more than glucose. This activates nerve cells of the vagus nerve, which relay signals from the gut to the brain. When this signaling pathway was blocked, the influence of fructose on the hunger neurons disappeared.

The new study thus provides a possible biological explanation for the observations from the 2015 human study: Although fructose and glucose contain the same number of calories, the brain apparently processes the two types of sugar differently–with possible consequences for hunger, satiety, and eating behavior.

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Study Context and Possible Limitations

A major advantage of the new study is that researchers were able to examine the biological processes between the gut, hormones, and brain in great detail. This allowed them to identify a specific mechanism that could explain the different effects of fructose and glucose.

Researchers also see indications that similar mechanisms could exist in humans. “There is evidence that fructose triggers a stronger release of the hormone PYY in humans than glucose–similar to what we observed in our study. Furthermore, neuroimaging data suggest that glucose reduces hypothalamic activity more than fructose. This also aligns with our findings in mice,” explains Amber L. Alhadeff, lead author of the study, in response to a FITBOOK inquiry.

The new study thus complements the 2015 findings with an important biological explanation. While the earlier study showed that fructose increases hunger and activates reward centers in the brain more strongly, the current work provides clues as to why this might be. Accordingly, fructose inhibits certain hunger neurons in the brain less strongly than glucose. Simply put: Although both types of sugar provide the same number of calories, glucose apparently sends stronger satiety signals to the brain. This effect is weaker with fructose, which could contribute to a longer-lasting desire to eat and stronger reward stimuli.

However, the complex neuronal analyses of the new study were conducted exclusively on mice. Therefore, it cannot be said with certainty whether all observed effects occur in humans in the same way. Additionally, while the 2015 human study included a solid number of participants for an fMRI study, the results need to be confirmed in larger and more diverse populations.

Conclusion

It also remains unclear what long-term effects these findings might have. The 2026 study shows that fructose affects the brain differently than glucose. Whether this increases body weight over time or influences the risk of metabolic diseases requires further investigation.

Despite the new insights, Dr. Alhadeff cautions against making blanket judgments about individual types of sugar. “We do not want to convey the message that certain types of sugar are inherently ‘good’ or ‘bad.’ However, we believe it is important for consumers to know that different types of sugar can have different effects on our bodies and brains.”