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J Biochem Mol Toxicol. 2018 Jun;32(6):e22053. doi: 10.1002/jbt.22053. Epub 2018 Apr 16.

Evaluation of long-term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study.

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Department of Physiology, School of Medicine, Istanbul Bilim University, İstanbul, Turkey.
Department of Physiology, School of Medicine, Ege University, Izmir, Turkey.
Department of Neurology, Faculty of Medicine, Trakya University, Edirne, Turkey.
Department of Histology and Embryology, School of Medicine, Ege University, Izmir, Turkey.
Department of Physiology, School of Medicine, Kafkas University, Kars, Turkey.


The aim of the present study was to compare the effects of artificial sweeteners (aspartame, saccharin, and sucralose) on rat brain. Twenty-four adult male Sprague-Dawley rats were included in the study. The control group (n = 6) received regular tap water, whereas other groups received aspartame (3 mg/kg/day, n = 6,) or saccharin (3 mg/kg/day, n = 6) or sucralose (1.5 mg/kg/day, n = 6) in the drinking water. Following 6 weeks, the passive avoidance learning (PAL) test was performed to evaluate the neurobehavioral effects of sweeteners. The brains were assessed for lipid peroxides, neuron count, and Glial fibrillary acidic protein (GFAP) immunohistochemistry. Our results demonstrated that chronic intake of sweeteners significantly impaired PAL performance in all groups. Hippocampal CA1-CA3 areas revealed significantly lower neuronal count in aspartame and increased GFAP expression in all groups. Brain lipid peroxides were significantly higher in all groups. Our findings suggest that long-term consumption of artificial sweeteners may have harmful effects on cognition and hippocampal integrity in rats.


artificial sweeteners; brain; oxidative stress; passive avoidance learning; rat

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