New study on mice links a commonly-consumed sweetener to an increase in anxiety for generations

It's a commonly used sweetener that can be found in soft beverages, frozen desserts, yogurt, etc.
Mert Erdemir
Stock image of a woman adding sweetener to her coffee.
Stock image of a woman adding sweetener to her coffee.


New research conducted by Florida State University scientists links aspartame, a commonly used artificial sweetener, with an increased risk of anxiety, according to a press release published by the institution.

Researchers tested the effects of aspartame on mice and found that it not only caused anxiety in the exposed animals but it also influenced up to two offspring of males that were exposed to the sweetener.

“What this study is showing is we need to look back at the environmental factors, because what we see today is not only what’s happening today, but what happened two generations ago and maybe even longer,” said co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences.

What is aspartame?

Aspartame is a low-calorie artificial sweetener that was approved by the U.S. Food and Drug Administration (FDA) in 1981. Since then, it's been used in about 5,000 different products. As a result of the fact that it's a low-calorie sweetener, it's widely used in diet sodas, light or low-sugar juices, flavored waters, or dairy products such as light yogurt and low-fat flavored milk.

As per the press release, aspartame breaks down into aspartic acid, phenylalanine, and methanol in the body, all of which can have potent impacts on the central nervous system.

In their clinical trials, researchers fed mice water with aspartame at a dosage that was around 15 percent of the FDA's recommended maximum daily amount for humans. For mice, this dosage is equivalent to consuming six to eight eight-ounce cans of diet soda a day for humans.

Continued for 12 weeks at this dosage, researchers observed more anxiety-like behavior in the exposed mice and the offspring of males for up to two generations.

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“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see,” Jones said. “It was completely unexpected. Usually, you see subtle changes.”


Then, when the research team gave mice diazepam, a drug used to treat anxiety disorder in humans, they observed that anxiety-like behavior halted in all generations.

The next step for researchers is to publish another article from this study that focuses on how aspartame affects memory. Future studies will pinpoint the molecular processes that affect how aspartame's effects are passed down through the generations.

The study was published in the journal Proceedings of the National Academy of Sciences.


We report the effects of aspartame on anxiety-like behavior, neurotransmitter signaling and gene expression in the amygdala, a brain region associated with the regulation of anxiety and fear responses. C57BL/6 mice consumed drinking water containing 0.015% or 0.03% aspartame, a dose equivalent of 8 to 15% of the FDA recommended maximum human daily intake, or plain drinking water. Robust anxiety-like behavior (evaluated using open field test and elevated zero maze) was observed in male and female mice consuming the aspartame-containing water. Diazepam, an allosteric modulator of the GABA-A receptor, alleviated the anxiety-like behavior. RNA sequencing of the amygdala followed by KEGG biological pathway analysis of differentially expressed genes showed glutamatergic and GABAergic synapse pathways as significantly enriched. Quantitative PCR showed upregulation of mRNA for the glutamate NMDA receptor subunit 2D (Grin2d) and metabotropic receptor 4 (Grm4) and downregulation of the GABA-A receptor associated protein (Gabarap) mRNA. Thus, taken together, our diazepam and gene expression data show that aspartame consumption shifted the excitation-inhibition equilibrium in the amygdala toward excitation. Even more strikingly, the anxiety-like behavior, its response to diazepam, and changes in amygdala gene expression were transmitted to male and female offspring in two generations descending from the aspartame-exposed males. Extrapolation of the findings to humans suggests that aspartame consumption at doses below the FDA recommended maximum daily intake may produce neurobehavioral changes in aspartame-consuming individuals and their descendants. Thus, human population at risk of aspartame’s potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals.