Dental caries is defined as a biochemical process in which dental tissues lost their minerals due to acidogenic pathogens which metabolize carbohydrates to produce acids [14]. This causes the pH value to be dropped below the critical value. As a result, calcium and phosphate ions are lost [15].
CPP-ACP is a compound developed to enable remineralization by generating a pool of calcium and phosphate which maintain the supersaturation of saliva [16].
A recent systematic review showed that there is an evidence regarding the remineralizing effect of CPP-ACP by studying the roughness of enamel. However, the effect on physiochemical properties of saliva has not been studied in this review[17].
Previous studies provided controversial results for the influence of CPP-ACP on physiochemical properties of saliva. For that reason, it is of interest to establish whether the application of CPP-ACP can raise the saliva pH or increase the salivary flow rate in children and consequently contribute to remineralization. To the best of our knowledge, this trial is the first to study the impact of topical application of CPP-ACP for a short period of time on the saliva pH and salivary flow rate in children.
Several studies have reported that the saliva pH can be changed due to variant factors such as metabolic, hormonal and general health changes [18, 19, 20]. However, decreased levels of saliva pH is an important indicator of developing dental caries [21].
Salivary flow rate can be defined as the amount of saliva secreted per minute. It can be considered as an important preventive aspect against demineralization since it protects and lubricates oral surfaces and facilitates the cleaning of bacterial substrates [22]. Consequently, reduced salivary flow can diminish the preventive capacity of saliva [21, 23]. However, a recent review recognized that there is a need to design further studies to make a reliable assessment between hyosalivation and dental caries in young patients [24].
Previous studies indicated that CPP-ACP can be used to inhibit demineralization and to improve remineralization. For instance, a recent review (2020) showed that CPP-ACP can be an effective agent to treat white spot lesions around orthodontic brackets. However, they found that the remineralizing effect of CPP-ACP is not significantly greater than using Fluoride alone [25]. This can be referred to what have mentioned Ferrazzano et al (2011) that the effect of CPP-ACP on demineralized enamel is affected by many elements in the oral cavity that are difficult to control [26].
Similarly, the study of Shen et al (2021) found that the presence of saliva and biofilm is crucial to authenticate the mechanism of action of CPP-ACP in remineralization [27]. The amount of secreted saliva and saliva pH can both alter the way CPP-ACP remineralizes tooth enamel as CPP separates from ACP in the acidic environment [28, 29].
In the present trial, 50 children aged 6 to 8 years old were selected since this age group has been at high risk of caries due to the cariogenic diet they consume[30]. In addition, a limited age range was selected to avoid the age-related differences in physiochemical properties of saliva.
To standardize the diet intake of the participants, all children recruited in this trial was lived in one orphanage. Stimulated saliva was selected to be studied in this trial in different time points before and after the application of CPP-ACP because stimulated saliva is more related with caries prevention than unstimulated saliva [31, 32]. This is due to the higher mineral content that leads to more buffering capacity and greater salivary clearance [31, 33].
In this study, saliva samples were collected in the morning (08:00–10:00 am) to minimize the effect of circadian variation in the salivary flow rate. saliva-check Buffer kit (Saliva-Check Buffer, GC Int) was used to check the salivary pH, as it was an easy to use, and reliable method [34]. In addition, the salivary pH was measured immediately after the determined contact time of the color-changing strip (10 s) to avoid potential misreading of the results. In this trial, there was no significant difference between the two intervention groups regarding the salivary flow rate. This may be attributed to the ability of the placebo cream to stimulate salivary secretion simply due to introducing a new agent into the oral cavity, considering the presence of any substance in the oral cavity induces both chemical and olfactory stimuli by neural reflexes, which leads to raised output of saliva.
Our results were different from those reported by Hegde and Thakkar(2017) which showed that CPP-ACP can increase the salivary flow rate [35]. This variation in the results can be due to the use of chewing gum in their study, which may increase the flow rate of saliva regardless of its composition. However, our results were in accordance with another study, which indicated that the topical application of CPP-ACP did not alter the salivary flow rate [36].
Moreover, this study showed that there was no significant difference between the two groups in the changes of saliva pH. This can be explained by the results of previous studies which indicated that CPP-ACP can increase salivary pH after a long period[37]. For instance, Ozdas et al (2015) showed that the increase buffering capacity of CPP-ACP was observed since the fourth week of application [38]. Therefore, our results were different from the results of Emamieh et al (2015) which showed that CPP-ACP containing chewing gum can increase the level of saliva pH [39]. This difference may be attributed to the duration of chewing the gum over three weeks assessed during the trial.
Padminee et al (2018) reported that CPP-ACP product can raise the pH of saliva more than xylitol. They attributed that results to the ability of CPP-ACP in bringing down Streptococcus mutans levels which are acidogenic pathogens [40].
The present findings indicated that both salivary flow rate and saliva pH were increased directly after the application of both placebo and CPP-ACP with a statistically significant difference between different time points. These findings were in agreement with of Prathima et al study (2021) which showed that maximum peak rise in salivary pH was observed immediately after spitting the CPP-ACP containing gums [41] de Oliveira PRA et al (2022) showed in their study that tooth remineralization of initial teeth demineralization gives better results in the presence of fluoride in conjunction with CPP-ACP. They also reported that placebo-treated specimens incorporated fluoride from the saliva due to the high sensitivity of white spot lesions (demineralized enamel) to pH cycling. For that reason, they found that remineralization process would be better achieved in the presence of fluoride dentifrice [7].
In fact, this study has highlighted the importance of investigating the remineralization products such as CPP-ACP for a short period among children. However, further studies should investigate the effect of CPP-ACP on a longer period of application to ascertain findings. In addition, future work should considers other parameters such as the measurement of calcium concentration, which might provide further understanding about the effect of CPP-ACP in remineralization process.