Long-term aspartame consumption affects global levels of DNA methylation in different types of rat tissues

BackgroundAspartame, a widely used artificial sweetener, is metabolized into phenylalanine, aspartic acid, and methanol. Previous studies have suggested that these metabolites may exert detrimental effects on the human body, particularly through alterations gene expression.AimThis study aimed to investigate the effects of long-term aspartame consumption on global DNA methylation levels in different tissues in order to evaluate the potential epigenetic mechanisms associated with low- and high-dose aspartame exposure.MethodsEighteen adult Long Evans rats were divided into three groups: control (n = 6), low-dose aspartame (50 mg/kg, n = 6), and high-dose aspartame (250 mg/kg, n = 6). Aspartame was administered daily via drinking water for 10 weeks. At the end of the 10^th week, the rats were sacrificed under anesthesia, and pancreas, liver, kidney, testis, and brain tissues were collected to determine global DNA methylation levels.ResultsHigh-dose aspartame consumption significantly increased the global 5-mC levels in the liver, kidney, and pancreas compared with the low-dose and control groups. No significant change was observed in global 5-mC levels in the testis. Interestingly, low-dose aspartame exposure increased the global 5-mC levels in the brain cortex, whereas high-dose aspartame did not produce a significant change.ConclusionThe present study provides the first in vivo evidence suggesting that prolonged exposure to high doses of aspartame may regulate gene expression by altering global DNA methylation levels in the liver, kidney, and pancreatic tissues.