Male mice fed the artificial sweetener aspartame at levels significantly lower than those deemed safe by the Food and Drug Administration (FDA) displayed deficits in learning and memory in a recent study.

What's more, these changes were also seen in their offspring, hinting at a long-term impact on intergenerational health.

US scientists tested the equivalent of up to 15 percent of the FDA daily aspartame limit on the mice, though it's important to note that doesn't mean this research will translate to humans.

Aspartame made headlines recently when WHO agencies classified it as possibly carcinogenic. Despite ongoing controversy, aspartame and other artificial sweeteners are considered safe at certain levels, and the team says their findings underscore that regulatory agencies should consider heritable effects as part of safety evaluations.

The health of future generations has traditionally been studied in relation to environmental exposures during pregnancy and breastfeeding. Biomedical scientist Sara Jones and her colleagues at Florida State University College of Medicine wanted to consider how males' environmental exposures may affect their offspring.

Two groups of male mice that consumed aspartame in their drinking water for 16 weeks at doses equivalent to 7 or 15 percent of the FDA's recommended maximum daily intake for humans were compared to a group of control mice fed plain drinking water.

Since it's estimated that the average human consumes only 4.1 mg/kg of aspartame per day, or 15 percent of the FDA's maximum daily intake value, the dose level was set to reflect this.

In tests of a number of cognitive functions, the mice that consumed aspartame exhibited significant spatial learning and working memory deficits. There were no significant differences observed between the two dose levels.

Male mice that had consumed aspartame were then bred with plain water-fed female mice. Male and female offspring of these mice also performed worse on spatial learning and working memory tests than offspring of mice that had not consumed aspartame.

One test required mice to find an escape box from 40 options in a circular arena. Aspartame-free mice found the box quickly, while aspartame-fed mice got there but took longer.

"We're seeing they use a different strategy, but they do find the escape box," says biochemist Deirdre McCarthy. "They compensate in some sort of way."

In a 2022 study, the same researchers found that aspartame consumption was associated with anxious behaviors in mice and in their offspring, for two generations.

"This is a cognitive function that is distinct from the anxiety behavior, so the effects of aspartame are much more widespread than the previous paper had suggested," explains neuroscientist Pradeep Bhide.

The researchers are still trying to figure out how aspartame affects the brain. They think changes in neurotransmitter signaling, particularly in the amygdala, possibly underlie the specific learning and memory deficits observed.

The authors suggest that aspartame's effects on cognitive function are domain-selective because they did not observe changes in reversal learning, memory retention, or recall.

"There is some overlap in terms of learning, memory and anxiety," Bhide says. "When there's an emotional impact, you remember better. But this is a quite distinct function and brain network."

Epigenetic changes (modifications to DNA that do not change the underlying genetic sequence) in sperm are thought to be a mechanism for the heritability of aspartame-induced traits.

"Unlike the anxiety (research), this went only one generation,' Bhide says, "which is another line of support that these kinds of transmissions occur due to epigenetic changes in the sperm."

More research is needed to confirm whether the findings translate to humans and determine the long-term consequences of aspartame consumption on cognitive function.

Artificial sweeteners such as aspartame are in a wide variety of processed foods and drinks, such as gum, soft drinks, protein bars, flavored syrups, and ice cream toppings. With the exception of people who already have diabetes, the WHO recently discouraged the use of artificial sweeteners for weight loss or disease prevention.

"A key public health implication of our findings," the authors conclude, "is that the population at risk of aspartame's adverse effects on learning and memory may be larger than current estimates, which consider the directly exposed individuals only."

The study has been published in Scientific Reports.