Researchers from the Florida State University College of Medicine have unveiled findings from an ongoing study revealing a potential link between aspartame consumption and learning and memory deficits in mice. 

Aspartame is an artificial sweetener widely used in various food and beverage products since the 1980s. It is commonly found in diet drinks, chewing gum, gelatin, ice cream, dairy products such as yogurt, breakfast cereal, toothpaste, and even medications such as cough drops and chewable vitamins.

The study raises questions about the safety of the artificial sweetener, as it demonstrates cognitive impairment effects at aspartame levels below the thresholds deemed safe by the U.S. Food and Drug Administration.

These results come just two months after the International Agency for Research on Cancer (IARC), the World Health Organization (WHO), and the Food and Agriculture Organization of the United Nations (FAO) and the Joint Expert Committee on Food Additives (JECFA) released their aspartame hazard and risk assessment results. The IARC classified aspartame as “possibly carcinogenic to humans” because of “limited evidence” for carcinogenicity in humans. Meanwhile, the JECFA reaffirmed the acceptable daily intake of 40 mg/kg body weight for aspartame.

Published in Scientific Reports, this research builds upon a previous study conducted by the Bhide Lab, which was published in the Proceedings of the National Academy of Sciences in December 2022. The earlier study associated aspartame consumption with anxiety in mice, with effects observed up to two generations. The current findings delve deeper into cognitive functions and reveal a distinct impact on learning and memory.

Co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences at Florida State University, told Florida State University News, “This is a cognitive function that is distinct from anxiety behavior, so the effects of aspartame are much more widespread than the previous paper had suggested.”

Methods
The study involved male mice and their offspring, which were exposed to aspartame at levels equivalent to only 7 percent and 15 percent of the FDA’s recommended maximum daily intake value. These levels mimic the consumption of 2 to 4 small 8-ounce diet sodas daily, representing a low-dose, long-term exposure scenario.

Over 16 weeks, the mice were subjected to various tests to assess their spatial learning and memory. One of the tests involved a Y-maze, while another used a Barnes maze, wher the mice had to locate a “safe” escape box out of 40 possible choices arranged in a circular arena.

Results
Results were starkly different between the control group, which consumed only water, and the groups that ingested aspartame. The aspartame-consuming mice took significantly longer to learn the spatial tasks, suggesting cognitive deficits.

Co-author Deirdre McCarthy, research faculty in the Department of Biomedical Sciences and the Center for Brain Repair, noted that the aspartame-exposed mice appeared to compensate for their learning and memory deficits. Bhide added, “They can function, but they need longer time, or may need extra help.”

Of particular interest is the observation that the cognitive deficits were only observed in the offspring of male mice that consumed aspartame. This suggests that the adverse effects of aspartame may be transmitted through epigenetic changes in the sperm, affecting the subsequent generation.

The study underscores the importance of considering the heritable effects of environmental exposures on cognitive function. While previous research has often focused on the impact of maternal exposures on future generations, this study highlights that environmental exposures of males may also have consequences for cognitive health in offspring.

The mechanisms underlying these heritable effects are not completely understood, but the study points to epigenetic changes in spermatozoa as a potential driver. Epigenetic changes are transient and reversible, which may explain why the effects observed in the mice were limited to one generation.

Further research is needed to better understand the precise mechanisms behind these cognitive deficits and to assess whether similar effects might occur in humans.