Treatment Type of study Methods Outcomes Ref/year Stannous fluoride products In vivo The groups were as follows: the test group using stannous fluoride products and the control group. The analysis showed no effect of stannous fluoride products. [37 ]/2018 Sodium fluoride dental protective agent combined with pit and fissure sealant In vivo The groups were as follows: in the control group pit and fissure sealant was used, and in the test group sodium fluoride tooth protector joined with pit and fissure sealant was used. The combined group had better results. [38 ]/2019 GI and RBS In vivo The groups were as follows: GI and RBS. Groups were the same in the survival of GI and RBS. [39 ]/2017 Ozone, sealant, and fluoride varnish In vivo The groups were as follows: (1) control; (2) fluoride varnish; (3) sealant; (4) ozone. The use of fissure sealant, fluoride varnish, and ozone is suggested for prevention of occlusal pit and fissure caries. [40 ]/2016 Silver diamine fluoride (SDF) In vivo SDF (38%) or Pl was applied topically. The primary outcome was caries arrest (Nyvad criteria). Topical 38% SDF was effective in arresting cavities. [41 ]/2018 RBS and GI In vivo The groups were as follows: RBS, GI sealant, and control. The RBS was higher than the GI sealant in prevention of caries. [42 ]/2018 F coating joined with PRF or PTS In vivo The groups were as follows: group A, PTS; B, PRF; C, 0.5% F coating + pit and fissure sealing; D, 0.5% fluoride + preventive resin filling; E, control. Groups C and A had a certain effect on prevention of dental caries, but group D was better. [43 ]/2018 Lactobacillus paracasei In vivo The groups were as follows: probiotic milk or control (standard milk). Probiotic milk reduced salivary S. mutans count. [44 ]/2018 MIV and MIPP In vivo The groups were as follows: FTP, using MIV + MIPP application, and control. Groups were the same in ICDAS scores and EDI sum. [45 ]/2018 CXT and FJ In vivo The groups were as follows: CXT or FJ. GIC sealants were effective in preventing caries. [46 ]/2018 PTS and FV In vivo The groups were as follows: resin-based fissure sealant or FV was applied. Groups were the same in caries prevention. [47 ]/2017 Xylitol-containing chewing gum In vivo The groups were as follows: in the test group xylitol gum + oral health education were used, and in control group oral health education alone was used. Both groups had a reduction in the caries rate. [48 ]/2017 MIn In vivo The groups were as follows: CE or MIn. MIn group was better in prevention of caries. [49 ]/2019 PTS combined with fluorine protective paint In vivo The groups were as follows: control, PTS, and PTS + fluorine protective paint. Pit and fissure sealant + fluoride protective paint can decrease the incidence of dental caries. [50 ]/2019 MIn In vivo The groups were as follows: HE, MIn, and MI + RA. MIn group had higher preventive effects against caries than HE group. [51 ]/2017 TiF4 varnish In vivo/in situ The groups were as follows: TiF4 varnish, Duraphat, Pl varnish, and no treatment. F-varnishes showed caries-preventive effect. [52 ]/2019 Silver NP + PTS In vivo/in situ The groups were as follows: conventional and silver NP combined with PTS. Silver NP mixed sealant was more effective than conventional sealant in reducing tooth demineralization. [53 ]/2017 Fluoride varnish In vivo The groups were as follows: fluoride varnish or Pl. Quarterly applications of fluoride varnish were not effective in preventing development of dental caries. [54 ]/2016 Different fluoride regimens In vivo The groups were as follows: G1: control group, fluoride (F) TP (1450 ppm); G2: FTP (1450 ppm) + 0.2% F oral rinse; G3: TP (5000 ppm). The recommendation was application of FTP (5000 ppm F) or oral rinse (0.2% NaF) + usual TPs. [55 ]/2019 Moisture tolerant RBS and GIS In vivo The groups were as follows: moisture tolerant RBS or GIS was placed on one side of the mouth, and the other one was placed on the opposing side. DIAGNOdent readings were taken. Both materials were effective in arresting enamel caries. [56 ]/2019 Fluoride varnish Duraphat In vivo The groups were as follows: fluoride varnish and control. Fluoride varnish Duraphat was effective in decreasing caries incidence. [57 ]/2019 Low-dose xylitol chewing gum In vivo The groups were as follows: xylitol and polyols. Xylitol group showed a significantly lower increment of dental caries. [58 ]/2017 RBS with and without F In vivo The groups were as follows: sealants with or without fluoride and control. The effects of the sealants were similar. [59 ]/2018 Xylitol and polyol chewing gum In vivo The groups were as follows: xylitol chewing gum, polyol chewing gum, and control group. Xylitol-containing chewing gum was effective in decreasing caries incidence. [60 ]/2018 Oral health education (OHE) and FV In vivo The groups were as follows: control, OHE, and OHE + FV. OHE or OHE + FV reduced the caries incidence. [61 ]/2016 FM and D In vivo The groups were as follows: participants brushed their teeth with either a D (1150 ppm) or a Pl D without F and either daily application of FM (220 ppm) or not. FM was effective in remineralization. [62 ]/2018 Biannual treatment with FV In vivo The groups were as follows: standard yearly intervention with or without FV. Biannual treatment with FV was not effective in preventing dental caries. [63 ]/2017 STB and S In vivo The groups were as follows: STB, CR sealant, and ART-GIC sealant. The groups were the same in preventing caries. [64 ]/2015 SDF 12% and SDF 38% In vivo The groups were as follows: 12% SDF applied yearly, 12% SDF applied twice a year, 38% SDF applied yearly, and 38% SDF applied twice a year. Higher concentration or frequency of SDF had more effect in arresting active tooth caries. [65 ]/2018 FV and peptide P11 -4 In vivo The groups were as follows: P11 -4 + FV or FV. P11 -4+FV was effective in early carious lesions. [66 ]/2018 CHX/thymol V or FV In vivo The groups were as follows: three-time monthly use of CHX/thymol varnish or semiannual use of FV + semiannual use of Pl V. The groups were the same in dental caries development. [67 ]/2015 FM, EO, and CHX oral rinses In vivo The groups were as follows: FM; EO; CHX; control (saline). FM and CHX had more effect than EO mouth rinse. [68 ]/2015 F, CPP-ACP, IR In vivo The groups were as follows: A, control (blank); B, control (Irr); C, Irr + F; D, Irr + CPP-ACP, E, Irr + CPP-ACP + F; F, Irr + IR; G, Irr + IR + F; H, Irr + IR + CPP-ACP. IR + CPP-ACP, IR + F, CPP-ACP + F, and IR were the best effective methods to prevent Irr-dentin-destructions. [69 ]/2019 TP containing Arg In vivo/in vitro Individuals wearing a dental device: the studies stages were lead-in, Arg-free, washout, and Arg-active stages. Arg-containing TP can significantly decrease the LA construction. [70 ]/2017 Varnish containing chlorhexidine In vivo The groups were as follows: Cervitec Plus® or Pl varnishes. Application of Cervitec Plus® had a significant advancement in patients’ oral health. [71 ]/2018 Herbal extracts (Tulsi and Black myrobalan) and sodium fluoride In vivo The groups were as follows: (1) FM, (2) Tulsi mouth rinse, and (3) Black myrobalan mouth rinse. Herbal mouth rinses could be tried as an anticaries agent for dental caries. [72 ]/2018 FV In vivo FV applied every three months. The use of fluoride varnish every three months prevented the incidence of caries. [73 ]/2019 Infiltrant application In vivo The groups were as follows: icon infiltrant (DMG) and PFS (Alpha Seal-DFL). The infiltrant was effective in preventing the caries progression comparable with the conventional sealant. [74 ]/2017 Fluoridated milk In vivo The groups were as follows: fluoridated milk and nonintervention. Consumption of fluoridated milk could significantly (34%) reduce the caries. [75 ]/2018 PRG filler-containing sealant placed with a self-etching primer/adhesive In vivo The groups were as follows: self-etch primed sealant (BeautiSealant, Shofu) or the etch and rinse sealant (Seal it, Spident). The groups were the same in caries prevention. [76 ]/2018 High-fluoride toothpaste In vivo The groups were as follows: 5,000 ppm F toothpaste or 1,450 ppm F toothpaste. High-fluoride toothpaste had more effects than control toothpaste in preventing caries. [77 ]/2019 FV In vivo The groups were as follows: FV or Pl. FV application was not effective in children. [78 ]/2018 MIn In vivo The groups were as follows: HE and MIn. MIn had more effect than HE in reducing caries. [79 ]/2018 Hydrophilic F-releasing sealant and ACP sealant In vivo The groups were as follows: Aegis™ or Embrace WetBond™ sealant. Aegis™ was more effective than Embrace WetBond™ sealant as Aegis™ demonstrated lower caries scores. [80 ]/2019 School-based fluoride varnish program In vivo Volunteers used FTP at home. The school-based fluoride varnish program prevented progression of caries. [81 ]/2016 Topical F In vivo The groups were as follows: (1) annual use of SDF solution (30%); (2) three-time use of SDF (30%) per week; (3) three-time use of 5% FV per week. Yearly use of SDF solution had more effect than three-time use of FV or SDF solution. [82 ]/2018 Nutrition and hygiene education In vivo The groups were as follows: intervention and control. The education intervention reduced the progression of caries. [83 ]/2018 Organoselenium-containing pit/fissure sealant (DenteShield™ (DS)) and UltraSeal™ XT Plus (UXT) In vivo The groups were as follows: DS and UXT. The groups had the same results for Caries prevention. [84 ]/2019 Fluoride TP In vivo/in vitro Volunteers used FD or not. FD group had lower demineralization. [85 ]/2016 Toothpastes with fluoride and hydroxyapatite In vivo The groups were as follows: toothpastes with hydroxyapatite and fluoride. Observation group had significantly higher ( > 0.05) acid resistance compared with the group of patients using fluoride toothpaste. [86 ]/2018 Ordinary and PB cake (Bacillus coagulans ) In vivo The groups were as follows: (1) 1-week consumption of PB cake, then 4-week washout period, and 1-week consumption of regular cake; (2) consumption of the cakes was reversed. The addition of PB bacteria led to a slight increase in the number of SM bacteria in the saliva. [87 ]/2019 Ordinary TB and an interactive power TB In vivo The groups were as follows: power TB with Bluetooth technology or an ordinary handy TB. An interactive power TB was more effective in plaque removal versus a handy TB. [88 ]/2019 Food enriched with probiotics In vivo The groups were as follows: PB milk and standard milk. The groups were the same in the incidence of caries. [89 ]/2018 Resin infiltration In vivo The groups were as follows: 1) FTP + flossing + infiltration; 2) control group (FTP + flossing). Infiltration group had better results than control group. [90 ]/2018 GI sand resin s In vivo The groups were as follows: GIS and RS. GISs presented effective prevention of caries development. [91 ]/2016 PB yogurt and gums with xylitol In vivo The groups were as follows: PB yogurt or gums with xylitol. The groups were the same in reduction of SM counts. [92 ]/2017 Fissurit FX sealant and Grandio Seal nanofilled fissure sealant In vivo The groups were as follows: Fissurit FX sealant and Grandio Seal nanofilled fissure sealant. Fissurit FX and Grandio Seal pit and fissure sealants were similar in caries prevention. [93 ]/2019 Photodynamic therapy and US In vivo The groups were as follows: PDT with MB and US. PDT or US postponed side effects. [94 ]/2018 Fluoride varnish or fluoride mouth rinse In vivo The groups were as follows: semiannual fluoride varnish applications (FV) and fluoride mouth rinses once per week (FMR). The groups had the same results in dental caries progress. [95 ]/2016 PB and normal milk In vivo The groups were as follows: PB milk and standard milk. Long-term drinking of probiotic milk may decrease caries progress. [96 ]/2016 Intensive FV In vivo The groups were as follows: 3 applications of FV in 2 weeks and extra applications at 1 and 3 months; FV treatment twice a year. The intensive FV application had no adequate effect to prevent dental caries. [97 ]/2018 Erythritol In vivo The groups were as follows: erythritol, xylitol, or sorbitol (control) group. Erythritol consumption had caries-preventive effect. [98 ]/2016 Interdental cleaning device In vivo The groups were as follows: manual toothbrush + mechanical interdental device or manual toothbrush alone. The combination group had a superior plaque removal compared to manual brushing alone. [99 ]/2018 FTP containing zinc ions In situ The groups were as follows: F, F/ZN/phytate, F/Zn, and F Pl. Phytate had slight effect on capability of fluoride to prevent more advanced lesion demineralization. Moreover, zinc ions had no bad effect on fluoride ability. [99 ]/2018 High-fluoride varnish In vivo The groups were as follows: differing frequencies of Duraphat varnish application. Periodic application of fluoride varnish could be useful in prevention of white spots. [100 ]/2016 Fluoride varnish In vivo The groups were as follows: control and use of FV (every 3 or 6 months). Results suggested using FV with three-month intervals for prevention of caries. [101 ]/2019 Fluoride varnish In vivo The groups were as follows: (1) dental hygiene + FTP and one-time use of three varnishes: Fluor Protector S, Elmex® fluid, or control (Pl). FV application had no extra protective benefit. [102 ]/2016 Toothpaste with nanosized sodium hexametaphosphate In vivo/in vitro The groups were as follows: conventional fluoride TP, fluoride TP (1100 ppm), fluoride TP (1100F + micro HMP), and fluoride TP (1100F + nano HMP). 1100F/HMPnano revealed a superior protective effect against enamel demineralization. [15 ]/2019 Three different compositions of topical fluoride varnishes In vivo The groups were as follows: FV having CPP-ACP; FV having xylitol; FV with 0.9% difluorosilane. FV having CPP-ACP showed higher decrease in SM count. [103 ]/2019 CHX MR, combination MR, and green tea extract MR In vivo Volunteers used different MR. Green tea mouth rinse was effective in prevention of caries. [104 ]/2017 Povidone-iodine (PI), CHX, or FV (fluor protector) In vivo The groups were as follows: PI, CHX V, or FV and control. Fluoride varnish showed higher decrease in S. mutans count. [105 ]/2017 Probiotic milk and fluoride mouth rinse In vivo The groups were as follows: probiotic milk and fluoride mouthwash. Groups were the same in reduction of S. mutans and PI scores. [106 ]/2019 Topical fluorides In vivo The groups were as follows: group 1, 30% SDF solution yearly; group 2, 30% SDF solution per week; group 3, 5% FV per week. Application of SDF had more effect on arresting caries than FV. [107 ]/2016 Milk sweetened with xylitol In vivo The groups were as follows: (a) xylitol milk, 8 g/200 ml, one time daily; (b) xylitol milk, 4 g/100 ml, two times daily; (c) sorbitol milk, 8 g/200 ml, one time daily; (d) sorbitol milk, 4 g/100 ml, two times daily; or (e) sucrose milk 8 g/200 ml, one time daily. There were no significant differences in caries incidence between groups. [108 ]/2016 Probiotic chewing tablets In vivo The groups were as follows: the test group got chewing probiotic tablet and the Pl group got the same tablets without bacteria. Probiotic chewing tablets could be helpful in reducing caries. [109 ]/2015 Fluoride TP In vivo The selected product was brushed twice daily for 4 months. Clinpro 5000, Clinpro Crème, and MI paste Plus all could be helpful in reducing white spot lesions. [110 ]/2019 Probiotic lozenge In vivo The groups were as follows: probiotic lozenge and Pl lozenge. Probiotic group had significantly lower S. mutans . [111 ]/2019 Self-etching adhesives having an AB agent and/or F In vitro/in vivo The groups were as follows: fluoride-containing (One-Up Bond F Plus, OP), MDPB and fluoride-containing adhesive (Clearfil Protect Bond, PB). The AB group had lower demineralization adjacent to restorations. [112 ]/2015 CPP-ACP and xylitol gum In vivo The groups were as follows: gum containing CPP-ACP and xylitol. Both gums increase saliva’s properties. [113 ]/2017 Resin infiltration In vivo The groups were as follows: test group lesions were treated with resin infiltration + 5% topical NaF application and control group with 5% NaF alone. Resin infiltration was more effective in reducing the development of initial proximal enamel lesions compared with the other group. [114 ]/2018 Salt fluoridation In vivo The groups were as follows: salt containing fluoride and control. Salt containing fluoride was more effective in prevention of caries. [115 ]/2018 Sodium fluoride varnish In vivo The groups were as follows: intervention group (fluoride varnish) and control group. Significant caries reversal was seen in primary dentition after intensive fluoride application after 1 year of study. [116 ]/2017 Sour cherry extract In vivo The groups were as follows: gum with cherry extract or control. Sour cherry extract may have effect on prevention of caries. [117 ]/2018 Arginine-containing TP In vivo/in vitro The groups were as follows: fluoridated TPs (FD) and arginine-containing fluoridated TPs (AFD). AFD had an anticaries effect like that of ordered fluoridated TPs. [118 ]/2018 PBM of major salivary glands In vivo The groups were as follows: continuous mode LED light, pulsed mode LED light, and control group. Results suggested that PBM of salivary glands reduces risk of caries. [119 ]/2020 Herbal mouthwash In vivo The groups were as follows: herbal mouthwash, chlorhexidine mouthwash, or Pl mouthwash. The effectiveness of herbal mouthwash in decreasing plaque formation was similar to chlorhexidine. [120 ]/2018 Filling intervention health education In vivo The groups were as follows: intervention group receiving filling of teeth; and health education group. Intervention group had better results. [121 ]/2015 CHX and F MR In vivo The groups were as follows: (a) CHX (0.12%) + NaF (0.2%); (b) NaF (0.2%); (c) CHX (0.12%); (d) control. Groups a and c had similar plaque formation. [89 ]/2018 Resin infiltration In vivo The groups were as follows: resin infiltration or control. Progression of caries was significantly higher in control versus infiltration group. [122 ]/2018 Probiotic Lactobacillus reuteri In vivo The groups were as follows: probiotic lozenges and Pl lozenges. Probiotic lozenges reduced bacterial counts significantly. [123 ]/2018 GIC sealant In vivo The groups were as follows: sealant application with or without extra light curing. Caries prevention in both groups was similar. [124 ]/2019 Propolis dental varnish In vivo Propolis varnishes were used in different concentrations (1%, 2.5%, 5%, and 10%). Propolis V has AM activity. [125 ]/2020 Resin infiltration In vivo The groups were as follows: infiltration and control. Resin infiltration was more effective in reducing caries progression. [126 ]/2016 GIS covered with resin-based agents In vivo Fuji VII was used and covered with G-Coat Plus or Heliobond. The results were the same in both groups in incidence of caries. [127 ]/2017 CPP-ACP In vivo The groups were as follows: stannous F gel (0.4%) with or without CPP-ACP. CPP-ACP was not effective in decreasing caries development. [128 ]/2015 New sealant In vivo The groups were as follows: Select Defense™ sealant; control. Test group had lower incidence of WSLs. [129 ]/2016 Atraumatic restorative treatment by chlorhexidine: disinfection or incorporation In vivo The groups were as follows: group (a) CHX having GIC; group (b) CHX; group (c) regular GIC. Both chlorhexidine disinfection and incorporation showed higher efficacy in inhibiting residual microbes compared to conventional ART. [130 ]/2017 Fluoride-releasing resin composite In vitro The groups were as follows: intervention group (F having adhesive resin) and control. The materials used in test group were not effective in prevention of WSL. [131 ]/2017 Fluoridated milk In vivo/in vitro Volunteers used an intraoral appliance. They dipped it in fluoridated milk for 5 minutes and once every other day drank the same milk. Drinking fluoridated milk once per day prevented enamel demineralization. [132 ]/2018 Toothbrush with paste and Munident In vivo The groups were as follows: normal TP and Munident. Munident (herbal) TP group had significantly lower S. mutans . [133 ]/2017 Fluoride TP and GC Tooth Mousse In vivo The groups were as follows: fluoride TP, CPP-ACP crème, and fluoride TP + CPP-ACP crème. All groups had the same results; combination groups did not have additive benefits. [134 ]/2020 MIPP and Er: YAG laser In vitro The groups were as follows: (a) MIPP; (b) Er: YAG laser; (c) MIPP + Er: YAG laser; (d) saliva; (e) control. Group c was the most effective group in the treatment of WSLs. [135 ]/2020 Probiotic bacterium Lactobacillus reuteri In vivo The groups were as follows: probiotic lozenge and Pl lozenge. Probiotic lozenges did not prevent progressing of WSL. [136 ]/2016 RMGI cement varnish In vivo The varnish was applied to teeth. Application of RMGI cement varnish could be useful in preventing WSLs. [137 ]/2015 Probiotic Streptococcus dentisani In vivo The probiotic was applied in a buccoadhesive gel. S. dentisani was able to buffer oral pH, especially after multiple dosing.[138 ]/2020 Semiannual fluoride varnish application In vivo The groups were as follows: typical oral health program with or without FV twice a year. Applications of FV + typical oral health program did not decrease caries progress. [139 ]/2016 CPP-ACP In vivo The groups were as follows: test group receiving CPP-ACP paste monthly and control group. Test group had lower WSL compared to the control patients. [140 ]/2016 Peptide P11 -4 In vivo The groups were as follows: P11 -4 or FV. Application of P11 -4 significantly reduced the size of early carious lesions. This reduction was higher than fluoride varnish application. [24 ]/2020 CHX MR and neem MR In vivo The groups were as follows: group a: CHX MR; group b: neem MR; group c: control. Both MR significantly decreased PI index. [141 ]/2017 TiF4 V In vivo/in vitro TiF4 , NaF (2.45% F), or control (Pl V). TiF4 V was the only treatment able to improve enamel remineralization. [142 ]/2017 Fluoride and sodium hexametaphosphate in toothpaste In vivo/in vitro TP having 1100 ppm F and 1100F + HMP1% and Pl. TP containing HMP1% was more effective than TP containing 1100F in decreasing demineralization. [143 ]/2015 Toothpaste Apadent Total Care medical nanohydroxyapatite In vivo Volunteers used Apadent Total Care toothpaste with nano-calcium hydroxyapatite. Application of toothpaste with nanohydroxyapatite showed the improvement of all indices. [144 ]/2016 Protective chlorhexidine varnish layer over resin-infiltrated proximal carious lesions In vivo The groups were as follows: in the test group infiltration + double layer of chlorhexidine varnish was used and in the control group only infiltration was used. Results suggest application of chlorhexidine varnish layer on resin infiltration when surface had microcavitation. [145 ]/2016 AgNO3 solution and FV In vivo The groups were as follows: (1) AgNO3 solution (25%) + FV; (2) SDF (38%) + Pl V. Results suggest application of AgNO3/NaF for management of ECC. [146 ]/2015 Tooth Mousse The groups were as follows: CPP-ACP (daily) and control. CPP-ACP reduced Streptococcus mutans in test group. [147 ]/2016 Fluoride rinse The groups were as follows: sodium F + amine F; control. Application of fluoride rinse helps prevent demineralization. [148 ]/2015