## 4 Discussion

Table 2: Results of subgroup analyses of serum vitamin D levels with dental caries. the conclusion was a low-certain evidence in favor of the positive effect of vitamin D supplements to reduce caries risk in children [31]. Furthermore, a systematic review by [PERSON] et al. found evidence of an association between low 25[OH] D levels (75 nmol/L) and caries experience in children [32]. Primary studies have uncovered conflicting data. According to our research, dental caries risk was inversely related to vitamin D status. Studies by [PERSON] et al. and [PERSON] et al. supported our findings by showing children with low vitamin D levels had increased dental caries [9; 26], additionally, [PERSON] et al. and [PERSON] et al. illustrated that there is a significant association between lower caries incidence in children and greater 25[OH] D levels [27; 63]. On the other hand, several studies found no link between children's oral caries experience and 25[OH] D levels [29; 30; 34]. The inconsistency between results could be because of diversity in age range, sample sizes, or race/ethnicity. However, subgroup analysis was conducted to see where the heterogeneity came from. The subgroup analysis indicated that age group and family income are heterogeneity sources. Reduced vitamin D serum levels were linked to higher risks of dental caries in all subgroups; however, they were not significant in all subgroups. A 10 nmol/mL increase in 25[OH] D levels, according to earlier research by [PERSON] et al. and [PERSON] et al., respectively, was associated with a 7% and 10% reduction in the likelihood of developing dental caries [18; 36]; these results support our findings, which showed that a 10 nmol/L rise in 25[OH] D concentration resulted in a 3% decrease in the risk of developing dental caries. Although the precise mechanism linking vitamin D to dental caries is not entirely understood, it has been stated that vitamin D improves calcium metabolism [64]. Plasma levels of calcium and phosphate are regulated by vitamin D during dentin development and promote mineralization by attaching to dental cells [65; 66]. Tooth surfaces demineralize by acid-producing bacteria, but vitamin D could maintain adequate calcium and phosphate levels in saliva for remineralization after demineralization [67]. Additionally, vitamin D has lytic activity against cariogenic bacteria [68], so an insufficient vitamin D level can cause development flaws in tooth structure and incomplete response to caries. Additionally, vitamin D is a vital agent in maintaining the balance of saliva electrolytes which could influence saliva production [69]. In addition, the higher risk of caries is due to lower flow and higher viscosity of saliva [70]. Furthermore, studies revealed that vitamin D regulates the immune system, causing the development of antimicrobial proteins such defensins, cathelicidins, and proteases that attack cariogenic bacteria [71; 72; 73]. Figure 6 summarizes the possible roles of vitamin D in caries prevention. The current study is an updated dose-response meta-analysis that examined the association between dental caries and vitamin D levels across all age groups, and thus the findings could be generalized to the entire population. We attempted to decrement the confounding effects and searched databases without language and time restrictions. Additionally, we only included studies that were carried out on healthy populations, conducted a one-stage weighted mixed-effects meta-analysis to ascertain a subgroup analysis to determine the effect of any potential confounding factors (such as race/ethnicity, sugar consumption, gender, and family income), conducted the Egger's asymmetry test to determine the impact of publication bias, and calculated the linear and non-linear relationships between the variables. Moreover, the evidence quality for the study outcome was evaluated utilizing the GRADE approach.