Could the sweetened drinks we’re consuming be making us feel a little more anxious? A new study looking at the effects of the artificial sweetener aspartame on mice suggests that it’s a possibility that’s worth investigating further.

Approved by the US Food and Drug Administration (FDA) in 1981, aspartame is widely used in low-calorie foods and drinks. Today, it’s found in nearly 5,000 different products, consumed by adults and children.

When a sample of mice were given free access to water dosed with aspartame equivalent to 15 percent of the FDA’s recommended maximum daily amount for humans, they generally displayed more anxious behavior in specially designed mood tests.

What’s truly surprising is the effects could be seen in the animals’ offspring, for up to two generations.

“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,” says neuroscientist Pradeep Bhide, from Florida State University in the US.

Anxiety was measured through a variety of maze tests on several generations of mice. The researchers also carried out RNA sequencing on key parts of their nervous systems to how the tissue’s genes were being expressed. The researchers found significant changes in the amygdala, a part of the brain associated with the regulation of anxiety.

We know that when it’s consumed, aspartame splits into aspartic acid, phenylalanine, and methanol, which can all affect the central nervous system. There have already been question marks over potentially adverse reactions to the sweetener in some people.

When the mice were given doses of diazepam – a drug once marketed as Valium, which is commonly used to treat anxiety in humans – anxiety-like behaviors stopped across all generations. The medication helps to regulate the same pathways in the brain that are altered by the effects of the aspartame.

Although monitoring for anxiety-like behaviors in mice is merely an approximation of similar moods in humans, the researchers observed clear changes in animal behavior, which they linked to changes in gene activity.

“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see,” says Sara Jones, a graduate research assistant at Florida State University. “It was completely unexpected. Usually you see subtle changes.”

The research follows on from earlier work by the same team on the generational effects of nicotine consumption on mouse behavior: again, those effects can apparently be passed down the generations due to non-coding epigenetic changes in the genes of mouse sperm cells.

Something similar could be happening here, the team suggests. In other words, it’s not just those who consume the artificial sweetener who might be at risk, but also their children and their children’s children. How that might happen is not yet fully understood, but fits with emerging evidence that suggests epigenetic markings can indeed remain intact across numerous generations.

Researchers have considered the links between aspartame and anxiety before, and though plausible, other animal studies have found no change in anxiety-like behavior in rats given artificial sweeteners, suggesting much more work needs to be done to understand what’s happening.

Even so, based on these results, Jones, Bhide and colleagues are urging caution. Past research has linked artificial sweeteners to cancer, and changes in the gut bacteria leading to glucose intolerance; anxiety is now perhaps another thing to consider.

While these same results still need to be replicated in human beings, having signs of anxiety in mice is a sound reason to investigate further.

“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,” write the researchers in their published paper.

“Thus, human population at risk of aspartame’s potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals.”

The research has been published in PNAS.