If you’re reading this article, you have probably had aspartame today. Aspartame, an artificial sweetener commonly found in diet sodas and other sugar-free products, is consumed by millions of people each day. Yet, there is still doubt about the safety of aspartame—even at levels well below the FDA’s recommended maximum daily intake.
As the correlation between aspartame consumption and risk for metabolic diseases and cancers becomes more widely recognized (WHO Advises Not to Use Non-Sugar Sweeteners for Weight Control in Newly Released Guideline, 2023), it is equally important to evaluate the possible effects of aspartame on cognitive abilities. When aspartame is digested, it is broken down into phenylalanine, aspartic acid, and methanol. Phenylalanine can cross the blood-brain barrier and is a precursor of the monoamine neurotransmitters dopamine, epinephrine, and serotonin. These three neurotransmitters control memory, mood, motivation, and motor function, which may explain how aspartame affects the central nervous system (CNS).
A study published this year in Nature sought to clarify how aspartame affects cognitive skills, specifically learning and memory abilities, and if the effects of aspartame are inheritable (Jones et al., 2023).The researchers chose to solely study male mice because there is less research concerning the heritability of cognitive defects from males.
The researchers used three groups of mice, each with a different level of aspartame in their water: 0.015% aspartame, 0.03% aspartame, and no aspartame (the control group). These levels are equivalent to 7-15% of the FDA’s daily limit, and thus reflect the amount of aspartame many people consume per day (about 2-4 small diet soda drinks). The mice were treated for 16 weeks to evaluate the effect of long-term aspartame exposure.
The first generation (F0) were tested for spatial working memory defects in weeks 4, 8, and 12 using a Y-Maze test. Mice have an innate curiosity to visit new arms of the maze instead of returning to ones previously visited. Hence, Y- Maze tests demonstrate the intact working memory of mice by seeing how well they remember the arms of the maze they already visited (Kraeuter et al., 2019). While there were no significant cognitive differences in the defects shown between mice of the 0.03% treatment group and the 0.015% treatment group, there were significant cognitive defects recorded for both groups of aspartame mice compared to the control group. The mice treated with aspartame were less likely to remember which parts of the Y-Maze they had already explored. However, no defects were found in relearning tasks or in learned helplessness evaluations between the groups.
Next, the researchers tested to see if the spatial working memory defect could be paternally passed down to the next generation of mice. The mice from each of the three groups (0.015% aspartame, 0.03% aspartame, and the no aspartame group) were bred with females who had been living of off plain drinking water. However, if they mated with an aspartame-treated mouse, the females unavoidably received the same aspartame water for 1-5 days during exposure. The researchers do not believe this was enough exposure to produce aspartame defects from maternal inheritability because there was no exposure during pregnancy or lactation. When the Y- Maze test was conducted for this next generation, the spatial working memory defect found in the F0 generation was passed down.
A third generation (F2) was also studied for possible transgenerational heritability. For this generation, the F1 mice from the 0.03% aspartame lineage and the control lineage were bred with female mice drinking only plain (non-aspartame) water. The 0.03% group was selected because it was the group with the largest exposure to aspartame, so any transgenerational effects would have been the most apparent. Nevertheless, the spatial working memory defect was not passed down across two generations.
Because spatial learning and working memory defects were seen in the F0 and F1 generations, the researchers believe the daily aspartame consumption impacted the mice’s amygdala. The amygdala regulates emotional functions, learning, and memory (Hermans et al., 2014), and thus is one region that could explain the observed effects. However, other brain regions are involved in spatial working memory, so more research needs to be done to conclusively establish the mechanism underlying the aspartame-induced behavioral changes.
While these results leave a lot of questions unanswered, they rightfully raise awareness concerning aspartame’s possible adverse effects. If the defects caused by aspartame are inheritable, the amount of people potentially affected by aspartame is far greater than currently recognized. The results of this study call for more research, especially on the long-term effects of aspartame at the levels people consume it.
So, maybe be a bit more cautious the next time you reach for a diet coke!
Literature Cited