Introduction: Aspartame is one of the synthetic sweeteners widely used in the food industry as a sugar substitute in recent decades. The present study aimed to investigate the effect of different doses of aspartame on histological and histomorphometric changes in the stomach in BALB/C mice.
Material & Methods: In this study, 24 BALB/C mice aged three weeks were selected and divided into three experimental groups that received 0.3 ml aspartame solution at doses of 100, 200, and 400 mg/kg body weight, and a control group that received drinking water with the same condition up to nine weeks of age. Eventually, some tissue sections were prepared from the stomachs and stained using the hematoxylin-eosin method. After histological evaluation, the necessary images were prepared and the histomorphometric examination was conducted using an optical microscope equipped with Axiovision software. The thickness of mucosa, submucosa, musculature, and depth of pits was measured and the frequency of parietal cells was calculated in the dimensions of 6.25 × 104 μm2.
(Ethic code: 7506001/6/7)  
Findings: Histological results indicated destruction and disruption of the mucosal epithelium and gastric pits and atrophy of gastric glands including glandular cells. In the histomorphometric examination of the non-glandular part, only the thickness of the mucosa had a significant difference in the group receiving the highest dose of aspartame compared to the control group (P<0.05). However, in the evaluation of the glandular part, mucosal and muscle thickness in all three experimental groups and the submucosa thickness in the glandular and non-glandular parts in the experimental group (400 mg body weight) showed a significant increase compared to the control group (P<0.05). Moreover, the depth of gastric pits increased significantly and the frequency of parietal cells had a significant decrease in the experimental groups compared to the control group (P<0.05).
Discussion & Conclusion: Although aspartame may partially play a protective role by decreasing parietal cells, it should be noted that higher doses of aspartame could induce tissue changes in different layers of the stomach. Therefore, it is recommended to use it with more caution.