In a year-long animal experiment, researchers for the first time evaluated the impact of the artificial sweetener aspartame on the body in a long-term, low-dose way that is close to reality, and found that it not only disrupts brain energy metabolism, but may also damage heart function, even if the intake is far below the "acceptable daily intake" currently set by major institutions.
The study was led by Spain's CIC biomaGUNE and the Biogipuzkoa Health Research Institute. The team supplemented mice with aspartame at a dose of 7 mg/kg of body weight, which is only about one-sixth of the upper limit recommended by the WHO, the European Medicines Agency and the US Food and Drug Administration (50 mg/kg/day) to avoid the limitations of previous studies that were too short and the dosage was too high. The experiment lasted for a year, with 18 mice taking aspartame for three consecutive days every two weeks, and 14 mice serving as a control group that did not take in the sweetener.
At the brain level, the researchers used FDG-PET imaging to track glucose uptake in the whole brain and specific brain regions. They found that after only two months of intermittent supplementation with aspartame, the glucose uptake in the brains of mice increased significantly, approximately twice that of the control group, indicating that the brain was in a "high energy consumption" state at an early stage. However, at about 6 months, this energy peak began to reverse. By 10 months, the glucose burning level in the brains of the aspartame-supplemented mice was about half lower than that of the control group, which meant that the brains, which relied almost entirely on glucose, were gradually "drained" of energy.
Overall, aspartame appears to shift the brain from short-term high energy mobilization to a long-term state of energy deficit, a pattern more likely to be associated with metabolic stress than an adaptive adjustment. Further magnetic resonance spectroscopy analysis showed that at two months, N-acetyl aspartate (NAA) in the cerebral cortex of the aspartame group, which reflects the metabolism and functional status of neurons, increased by about 13%. However, after 4 months, this "positive" signal disappeared and continued to worsen; by 8 months, the lactic acid level in the aspartame group was approximately 2.5 times that of the control group, indicating a disorder in cellular energy metabolism.
Research points out that this is closely related to the metabolic relationship between astrocytes and neurons: Astrocytes are responsible for converting glucose into lactic acid that is more easily utilized by neurons to supply these energy consumers. However, when lactate remains at a high level for a long time, neurons are difficult to use effectively. Lactic acid begins to accumulate locally, breaking the energy balance in the brain and causing the brain to enter a similar "emergency mode." The work efficiency of related neural circuits decreases, and learning speed, mental tolerance, and complex task processing capabilities may be affected.
To verify this, the team used the Barnes maze to conduct spatial learning and memory tests. The results showed that at 4 months, mice supplemented with aspartame moved slower and traveled shorter distances during training, and the average time it took to find an escape hole was nearly twice that of the control group, but this difference was not statistically stable. By the 8th month, the performance gap between the two groups further widened. Two mice in the aspartame group even failed to complete the task. The overall performance was consistent with the aforementioned metabolic changes, reflecting that their ability to solve problems and perform tasks was weakened by long-term intake of aspartame.
The effects are not limited to the brain. Cardiac imaging examinations showed that at the end of the trial, the cardiac structure and function of mice supplemented with aspartame showed significant changes. The ventricular ejection efficiency decreased and the blood output per contraction decreased. Although the damage to the naked eye and structure was not serious, the blood pumping function was weakened. In the long term, this means that various organs, including the brain, receive a slightly insufficient supply of blood and oxygen, which may further exacerbate the metabolic burden.
In terms of body weight and fat distribution, the study found that the total fat mass accumulated in the aspartame group mice within one year was about 20% lower than that of the control group, but this "fat loss" did not translate into better metabolic health indicators. Although the weights of the two groups were similar, the fat distribution in the aspartame group gradually tilted toward visceral fat, with an increase in the proportion of fat surrounding organs and a decrease in lean body mass. This pattern is believed to put greater pressure on the heart and metabolic system, and partly explains the changes in heart function and brain energy utilization.
The research team concluded that aspartame can indeed reduce fat deposition by about 20% in mice, but at the expense of mild cardiac hypertrophy and reduced cognitive performance; in other words, while this sweetener "reduces fat" in animal models, it is accompanied by pathophysiological changes in the heart and possibly the brain. However, the authors also emphasized that a significant limitation of this study is that it is currently only based on animal models, and the long-term effects in humans have yet to be confirmed. However, the results highlight the importance of conducting longer-term studies on widely used sweeteners such as aspartame that are close to daily intake levels.
Since first being approved by the U.S. FDA in 1974, aspartame (L-aspartyl-L-phenylalanine methyl ester) has become one of the most dominant artificial sweeteners in the U.S. market and is widely used in an estimated 6,000 foods and beverages. Multiple studies in the past have suggested that it is associated with health risks such as serious heart problems and reduced learning and memory functions. This long-term experiment further provides new evidence clues for this potential risk from the two dimensions of brain energy metabolism and heart function.