Long-term aspartame intake sabotages brain and heart function

In the first long-term and real-world reflective study of its kind, scientists have uncovered new detrimental health impacts of the artificial sweetener aspartame that echoes those found in shorter research.

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.

Looking at things on a biochemical level, the researchers used magnetic resonance spectroscopy to examine metabolites in the cerebral cortex. Again, after two months, levels of N-acetylaspartate (NAA) – a marker of neuronal metabolism and function – were about 13% higher in the aspartame group. However, by four months, early positives again vanished and continued to worsen. At eight months, lactate levels were around 2.5 times higher in aspartame-treated mice, suggesting cellular dysfunction.

To fully understand the process you have to know the relationship between astrocytes – the star-shaped cells that convert glucose to lactate – and the neurons they support. Neurons are both energy hungry and bad at managing fuel, which is where astrocytes come in, converting glucose to easily-burned lactate to feed the nerve cells (the astrocyte-neuron lactate shuttle). However, when there's a consistent high level of lactate, neurons can't use it efficiently and it begins to accumulate, messing up the energy balance in the brain. Essentially, this puts the brain in "emergency mode," making neural circuits less efficient, potentially slowing learning, reducing mental stamina and attention and making complex tasks harder.

When the researchers conducted spatial learning and memory tests using the Barnes maze, the aspartame mice at four months consistently moved more slowly and covered less distance during training than animals in the control group. They also took nearly twice as long on average to locate the target escape hole, showing impaired memory recall (however, this was inconsistent and not seen as statistically meaningful). By eight months, performance gaps widened even further, with two out of six aspartame-treated mice failing to complete the task at all.

Overall, long-term aspartame intake appeared to hamper the animals' ability to follow through with problem-solving tasks, in line with the metabolic changes that the researchers had uncovered in the brain.

But it wasn't just the brain that was affected. Cardiac imaging revealed significant changes in heart structure and function by the end of the study. The hearts of aspartame-treated mice didn’t pump as efficiently – the chambers emptied less completely and delivered less blood with each beat, even though there was little structural damage. Over time, that means organs – including the brain – received slightly less blood and oxygen.

The researchers also found that while aspartame-treated mice accumulated about 20% less total body fat than the control animals over the 12 months, this reduction didn't translate into improved metabolic health. Despite similar body weights, fat distribution shifted over time, with a greater proportion of fat stored viscerally around the organs and less lean mass overall. This type of fat redistribution is known to place greater strain on the heart and metabolism, helping explain why reduced fat mass in these mice coincided with changes to the heart and brain energy use.

"Aspartame does indeed reduce fat deposits (by 20%) in mice, but it does so at the cost of mild cardiac hypertrophy and decreased cognitive performance," the researchers confirmed. "Although this sweetener may help achieve weight loss in mice, it is accompanied by pathophysiological changes in the heart and, possibly, in the brain."

The obvious limitation to the study is that the results are based on an animal model, and are yet to be demonstrated in humans. However, it highlights the importance of long-term experiments to further our understanding of chronic aspartame intake and how it might influence brain and heart metabolism.

Since its initial FDA approval in 1974, aspartame (L-aspartyl-L-phenylalanine methyl ester) has become one of the leading artificial sweeteners on the US market. Numerous studies have highlighted health concerns associated with it, including serious heart problems and learning and memory impairment.

The study was published in the journal Biomedicine & Pharmacotherapy.

Source: CIC biomaGUNE