Tehran University of Medical Sciences Frontiers in Dentistry 2676-296X 18 0 2021 04 07 3090 3090 Farnaz Farhad Department of Pediatric Dentistry, School of Dentistry, Arak University of Medical Sciences, Arak, Iran Sohrab Kazemi Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical Sciences, Babol, Iran Ali Bijani Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran Nilgoon Pasdar Dental Material Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran 2019 04 06 2020 12 02 Objectives: This study investigated the efficacy of theobromine in comparison with 0.05% sodium fluoride solution for remineralization of initial enamel caries lesions (IECLs). Materials and Methods: Ninety non-carious extracted premolars were sectioned longitudinally into buccal and lingual segments. Caries-like lesions were induced in each segment using acidified gel.  Forty-five buccal segments were used for surface microhardness (SMH) test, and 45 buccal segments were used for energy-dispersive X-ray spectroscopy (EDS). The lingual segments were used as the control group for EDS and SMH test. The baseline SMH was measured with a Vickers hardness tester, and the baseline calcium content was analyzed by EDS. Each test group was divided into three subgroups for treatment with (1) artificial saliva, (2) 1.1 mol/L theobromine, and (3) 0.05% sodium fluoride. Remineralization and demineralization were done by daily pH cycling to simulate the oral environment. Samples in each group were immersed in treatment solutions for 1 min before and after the remineralizing cycle. After a 7-day cycle, the SMH test and EDS analysis were performed again. Data were analyzed using one-way ANOVA, Tukey’s post-hoc test, and paired sample t-test (P<0.05). Results: All treatments effectively remineralized the IECLs (P<0.05), and theobromine caused the maximum increase in SMH, which was significantly higher than the value in sodium fluoride group (mean value of 36.56±4.95 versus 23.25±3.92; P=0.000). EDS showed the highest calcium deposition in theobromine group (3.82±1.83wt%). Conclusion: Theobromine is an effective cariostatic agent, and can be considered as a safe alternative to fluoride in preventive dental care. https://fid.tums.ac.ir/index.php/fid/article/view/3090 https://fid.tums.ac.ir/index.php/fid/article/download/3090/1846