Aspartame and Its Metabolites Cause Oxidative Stress and Mitochondrial and Lipid Alterations in SH-SY5Y Cells

• Published in: Nutrients 2023-03, Vol.15 (6), p.1467
• Main Authors: Griebsch, Lea Victoria, Theiss, Elena Leoni, Janitschke, Daniel, Erhardt, Vincent Konrad Johannes, Erhardt, Tobias, Haas, Elodie Christiane, Kuppler, Konstantin Nicolas, Radermacher, Juliane, Walzer, Oliver, Lauer, Anna Andrea, Matschke, Veronika, Hartmann, Tobias, Grimm, Marcus Otto Walter, Grimm, Heike Sabine
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amino acids; Aspartame; Aspartame - metabolism; Aspartame - pharmacology; Aspartic acid; Brain; Cardiolipin; Causes of; Cell culture; Degeneration; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Enzymes; Ethanol; Fluorescence; Gene expression; Glucose; Health aspects; Health services; Homeostasis; Humans; lipid droplets; Lipid metabolism; Lipid peroxidation; Lipids; Lipids - pharmacology; Memory; Metabolic disorders; Metabolism; Metabolites; Microscopy; Mitochondria; Nervous system; Neuroblastoma; Oxidative Stress; Phenylalanine; phosphatidylcholine; Phosphatidylethanolamine; Phospholipids; Physiological aspects; PTEN-induced putative kinase; ROS; Substitutes; Sugar; Superoxide dismutase; Sweetening Agents - pharmacology; synthetic sweetener; Triglycerides
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15061467

Due to a worldwide increase in obesity and metabolic disorders such as type 2 diabetes, synthetic sweeteners such as aspartame are frequently used to substitute sugar in the diet. Possible uncertainties regarding aspartame's ability to induce oxidative stress, amongst others, has led to the recommendation of a daily maximum dose of 40 to 50 mg per kg. To date, little is known about the effects of this non-nutritive sweetener on cellular lipid homeostasis, which, besides elevated oxidative stress, plays an important role in the pathogenesis of various diseases, including neurodegenerative diseases such as Alzheimer's disease. In the present study, treatment of the human neuroblastoma cell line SH-SY5Y with aspartame (271.7 µM) or its three metabolites (aspartic acid, phenylalanine, and methanol (271.7 µM)), generated after digestion of aspartame in the human intestinal tract, resulted in significantly elevated oxidative stress associated with mitochondrial damage, which was illustrated with reduced cardiolipin levels, increased gene expression of SOD1/2, PINK1, and FIS1, and an increase in APF fluorescence. In addition, treatment of SH-SY5Y cells with aspartame or aspartame metabolites led to a significant increase in triacylglycerides and phospholipids, especially phosphatidylcholines and phosphatidylethanolamines, accompanied by an accumulation of lipid droplets inside neuronal cells. Due to these lipid-mediating properties, the use of aspartame as a sugar substitute should be reconsidered and the effects of aspartame on the brain metabolism should be addressed in vivo.