High-Fructose Diet Harms Neurodevelopment and Leads to Anxiety in Mice, MSK Study Finds

Diets high in fructose have been under the microscope for their contribution to increasing rates of obesity, diabetes, and other metabolic diseases. Recent evidence suggests the negative effects may also extend to mood and anxiety disorders, especially in adolescents.

Now, a new laboratory study from Memorial Sloan Kettering Cancer Center (MSK) is shedding light on the mechanisms by which high fructose consumption early in life may directly impact brain development and increase the risk of anxiety disorders later on.

The findings were published June 11 in Nature, one of the world’s premier scientific journals.

The researchers — led by first author Zhaoquan “Shasha” Wang, PhD, a graduate student in the lab of senior author Justin Perry, PhD, in MSK’s Sloan Kettering Institute — found that when pregnant mice and newborn mice were given high levels of fructose, the pups showed a decline in an essential neurodevelopmental process called phagocytosis. Phagocytosis is the process by which specialized immune cells in the brain called microglia eliminate surplus neurons and miswired connections — a critical function in brain development.

In people, this “synaptic pruning” starts in early childhood and continues into one’s 20s, Dr. Perry says. Meanwhile, the mice used in the study reach adolescence in about six weeks.

“High-fructose corn syrup can be found in many fast foods and processed foods, and is a common sweetener in sodas,” he says. “And while some recent studies have found correlations between fructose consumption and mental health impacts, our study uncovered a biological mechanism that may explain those observations.”

Fructose Transporter Protein GLUT5 Identified as a Key Player

For the study, the researchers looked at the impact of a high-fructose diet on brain development in mice — both in offspring born to mothers fed fructose as well as neonates given the extra sweetener directly.

“The amount was roughly equivalent to a soda a day in people,” Dr. Perry notes.

In both cases, the researchers saw reduced phagocytosis in the developing mice.

The team discovered that the negative effects on the brain were dependent on a protein called GLUT5, which transports fructose molecules across cell membranes. When they genetically manipulated the mice to remove GLUT5 — both globally and also just in their microglia cells — the dysfunction did not develop.

“One question we had was whether you’d be protected if you’re exposed during pregnancy but then had a low-fructose diet afterwards, or vice versa,” says Dr. Wang, who was recently awarded his doctorate from Weill Cornell Medicine’s Immunology and Microbial Pathogenesis program. “And, unfortunately, our experiments found the same developmental impacts in both sets of mice.”

Moreover, the study found mice exposed to high fructose in the womb and as newborns displayed anxiety-like behavior once they grew into adolescents.

To test this, the researcher paired a startling stimulus — such as a loud sound — with a mild electric shock. When the shock component was taken away, normal mice would eventually get used to the sound, but the mice who were fed the high-fructose diet when they were young did not show the normal drop-off in their fear response.

Fructose-fed mice engineered to lack GLUT5 also did not have a lingering fear response — highlighting the protein’s critical role.

Next Steps and Implications for Cancer

Overall, the findings point to potentially profound implications about the impact of high-fructose diets during pregnancy and adolescence in people, the researchers say.

“High fructose consumption alone likely does not cause the development of mood or anxiety disorders, but it may play an unrecognized contributing role,” Dr. Perry says. “Our research shows for the first time how this very common ingredient in the modern, Western diet directly impacts neurodevelopment. And, given the recent rise in mood and anxiety disorders, how this may factor into adolescent development remains an important public health question.”

Trying to change people’s dietary habits is extremely difficult, Perry notes, so the lab is now investigating whether fructose analogs — compounds with slight variations in their composition — might avoid the sweetener’s deleterious effects.

Additionally, GLUT5 is significantly or completely lost in diseases of the brain, including Alzheimer’s and glioblastoma, an aggressive brain cancer, he adds.

“GLUT5 expression actually increases as we age,” Dr. Perry says. “So we’re working to better understand its normal function in healthy aging and its role in brain diseases associated with later life.”

Additional Authors, Funding, and Disclosures

The study was authored by 26 researchers from five institutions. Please refer to the article for the full list.

This work was supported by grants from the National Cancer Institute (5R00CA237728, 1R01CA248364, 5T32CA009149, 5T32CA254875-03, P30CA008748); the National Institute of General Medical Sciences (1DP2GM146337); a Pew Biomedical Scholars Award; and the National Institute of Allergy and Infectious Diseases (5T32AI134632).

Two of the authors, Dr. Perry and Kayvan Keshari, PhD, are co-founders of Atish Technologies. Both researchers hold patents related to imaging and modulation of cellular metabolism. Dr. Keshari additionally serves on the scientific advisory board of NVision Imaging Technologies.

Read the study: “Early life high fructose impairs microglial phagocytosis and neurodevelopment,” Nature. DOI: 10.1038/s41586-025-09098-5