A research team led by Spain's CIC biomaGUNE and Biogipuzkoa Health Research Institute undertook a year-long study into the effects of aspartame on the body, limiting the dosage to well below current Acceptable Daily Intake (ADI) guidelines. This experimental design was a deliberate effort to rule out two key limitations that hamper existing evidence: brief study periods and unrealistically high dosage levels.

While aspartame is one of the most studied food additives on the planet, short studies can show mechanistic impacts of aspartame but not long-term effects – and this is one reason why bodies like the World Health Organization (WHO), despite classing aspartame as "possibly carcinogenic to humans" in 2023, and the US Food and Drug Administration (FDA) have deemed it safe when consumed below the ADI threshold.

Here, the team exposed mice to 7 mg/kg (3.17 mg/lb) of body weight in human equivalent – around one-sixth of the maximum recommended daily intake – over the period of a year. Eighteen mice were given aspartame for three days every two weeks, alongside a no-dose control group of 14 animals.

"We are observing how nutrient modulation impacts organ function in sickness and in health, and in this case, we set out to determine the physiological impacts aspartame exerts on the hearts and brains of mice, as well as its effect on fat levels and body weight, in order to compare them with other types of sugars and sweeteners," the researchers noted. "This dose is well below the maximum dose recommended by the World Health Organization, the EMA (European Medicines Agency) and the FDA (Food and Drug Administration), which is 50 mg/kg (22.7 mg/lb) per day."

Over the course of the year-long experiment, the most significant changes were seen in how the brain processed energy. Using FDG-PET imaging, the researchers tracked glucose uptake across the whole brain as well as specific regions, and found that after only two months of intermittent aspartame intake, the mice had sharp rises here – roughly double that seen in the control group. And this effect was across the entire brain, suggesting it was burning more fuel in the early stages of the experiment. However, at around six months, this spike actually reversed, and at the 10-month mark, the brains of the aspartame-dosed mice were burning around 50% less glucose than the control group. Because the brain runs almost entirely on glucose – to fuel processes like the firing of neurons and maintaining circuits linked to memory and learning – aspartame appeared to be robbing the organ of what it needs to function smoothly.

In real-world terms, aspartame appeared to cause the brain to shift from an early state of heightened energy use to a more chronic state of underuse – which is a pattern often associated with metabolic strain, not adaptation.