Kinetics of fluoride after brushing with the no-rinse method.

This study investigated the kinetics of fluoride in healthy adults following the use of 1500 ppm sodium fluoride toothpaste, specifically employing the no-rinse method after brushing. The research aligned with the recommendations of several dental associations, including the Australian Dental Association, British Dental Association, Nation Health Service (NHS.UK), and Canadian Dental Association, all of which advise against rinsing after brushing. However, there is currently limited data available regarding its efficacy and safety. To bridge this gap, this study compared the no-rinse and rinse methods to assess their impact on fluoride concentrations in supernatant, sediment, and whole saliva. Blood and urine samples were collected at various time points to comprehensively evaluate fluoride absorption to the systemic circulation and excretion. Our findings showed that the no-rinse method resulted in higher levels of fluoride in saliva than the rinse method, particularly immediately after brushing and up to 5 min afterward. Examining saliva components, we found that fluoride concentration peaked in the supernatant immediately after brushing and gradually moved to the sediment. Despite higher salivary fluoride, fluoride levels in plasma and urine are below those observed in patients with fluorosis, suggesting the safety of the no-rinse method after a single brushing.

The no-rinse method consistently resulted in higher fluoride concentrations in both the supernatant and sediment immediately after brushing, and in the supernatant at subsequent time points, compared to the rinse method. A prior study indicated that no-rinsing after brushing with sodium fluoride resulted in higher salivary fluoride levels than the rinse method until 1 min [16]. In contrast, our study showed that using the no-rinse method with sodium fluoride toothpaste sustained greater fluoride levels in the whole saliva for up to 5 min, longer than previously reported. The duration of fluoride exposure in the oral cavity directly influences its effectiveness in promoting remineralization of enamel or dentin. Longer exposure allows fluoride to exert its protective and strengthening effects, contributing to oral health and reducing the risk of tooth decay [18, 19]. If the no-rinse method consistently extended the level of fluoride over 5 min over a period of time, it might show significant remineralization and reduce the incidence of caries. Furthermore, we found that fluoride levels in the supernatant after using the no-rinse method reached the concentrations required to inhibit 50% demineralization (0.3 to 0.4 ppm) [20] for up to 30 min, whereas the rinse method maintained these fluoride levels for up to 15 min after brushing. Our findings align with previous studies, which demonstrated that the no-rinse method maintained salivary fluoride retention in the oral cavity better than the rinse method [21]. Additionally, increased rinsing water decreases fluoride retention in the oral cavity, leading to lower salivary fluoride levels and potentially higher dental caries incidence [9, 12]. Thus, minimizing rinsing after brushing may enhance fluoride efficacy.

This study separated whole saliva into supernatant and sediment components to examine how the rinsing methods (no-rinse Vs. rinse) impact fluoride’s kinetics in both saliva compartments. This approach is crucial as these compartments may influence the bioavailability of fluoride differently within the oral cavity. The cell-free supernatant saliva represents a complex secretion originating from the salivary glands. At the same time, the sediment comprises the bulk of the human oral microbiome, cellular constituents, proteins, and food particles [22]. At baseline (before brushing), fluoride accumulated more in the sediment. Immediately after brushing, fluoride was initially distributed in the supernatant in both methods. However, fluoride levels became more prominent in the sediment after 60 min post brushing. This pattern was observed with the no-rinse and rinse methods at 60 min, but only the no-rinse method maintained elevated fluoride levels in the sediment for up to 90 min, indicating that this effect might be more noticeable with the no-rinse method. Our findings align with previous research showing a biphasic clearance pattern, with rapid fluoride declines in the first 40–60 min followed by a slower decrease [23, 24]. The gradual decline after 60 min may result from sustained fluoride release from the sediment reservoir, suggesting it acts as a fluoride reservoir in the oral cavity that could help prevent demineralization [22, 25].

Besides the fluoride reservoir in the sediment, fluoride retention in the saliva is also influenced by other factors, including fluoride levels in the mouth, salivary flow rates, toothpaste fluoride content, rinse method, and fluoride clearance rates [16, 21, 26,27,28,29]. Salivary flow rate affects fluoride concentration in the oral cavity because a high salivary flow rate increases fluoride clearance and may reduce its concentration in the oral cavity [26]. In our study, the calculated salivary flow rate was 0.58?±?0.20 ml/min, slightly higher than the typical unstimulated rate of 0.3–0.4 ml/min [30]. This higher rate could be a factor to consider, but our crossover design helps mitigate its impact.

We also determined a kinetic parameter, the AUC of salivary fluoride, for both post-brushing methods since AUC measures fluoride’s oral bioavailability. Our findings revealed a notably higher AUC in the no-rinse group compared to the rinse groups. A clinical study demonstrated the impact of water rinsing on salivary fluoride AUC, showing that the AUC of salivary fluoride was 2.5 times lower when water rinsing was used [11]. Therefore, our findings suggest that the no-rinse brushing method increases fluoride retention in the oral cavity and potentially lowers the risk of caries.

Absorption of high fluoride intake into the plasma is associated with the risk of dental and skeletal fluorosis. Fluoride toxicity poses serious health risks, leading to dental issues and cognitive impairment in children [13, 14, 31,32,33]. Dental fluorosis has been reported in individuals aged 1 to 23 years, with younger people being more susceptible [34,35,36,37,38,39,40,41]. While dental fluorosis is less common in adults, fluoride absorption can lead to skeletal fluorosis in adults [14, 40, 42, 43]. In addition, children aged 6 to 13 years have been diagnosed with this condition [44]. These conditions arise due to the absorption of high fluoride levels into the plasma.

Preventive measures and monitoring of fluoride exposure are crucial. Despite advocacy for the “spit, no-rinse” brushing method to preserve fluoride levels in the oral cavity, concerns about fluoride accumulation and the risk of fluorosis remain. Our study aims to assess fluoride concentration in plasma to validate the safety of the no-rinse method. Measuring plasma fluoride reflects systemic absorption, while urine fluoride indicates elimination. Previous studies have focused on sodium lauryl sulfate (SLS) toxicity to oral tissues [45, 46] and assumed low SLS content in toothpaste is safe with the no-rinse method [47, 48]. However, there is no evidence documenting systemic fluoride absorption with this approach. Our study aims to provide concrete data on fluoride absorption by including urine and blood evaluations for a comprehensive safety profile of the no-rinse method.

As fluoride toxicity arises from high fluoride absorption into plasma, analyzing plasma fluoride levels is an approach to assess the safety of the no-rinse method. To minimize intrusion, we collected blood samples at a single time point, 1 h after brushing, based on fluoride’s absorption half-life of 30 min [49]. This timing allowed us to estimate peak fluoride absorption. Our study observed similar mean blood fluoride levels of approximately 0.02 ppm for both the no-rinse and rinse methods. These levels are below those reported in patients with dental and skeletal fluorosis (0.16–1.25 ppm) [13, 50]. A study demonstrated that less water use for rinsing leads to higher fluoride absorption into the plasma [51], as well as The United States Environmental Protection Agency (EPA) states that a higher amount of fluoride exposure is linked to the severity of fluorosis [52, 53]. Our results showed that even though the no-rinse method leads to higher fluoride exposure, the plasma fluoride levels remained within the safety limit (0.02 ppm) [50] and were similar to those observed with the rinse method. This data provides insights into the safety of the no-rinse method after a single brushing. However, further long-term studies are needed to assess the effects of repeated use of no-rinse toothpaste formulas compared to rinsing methods.

Since urinary fluoride directly reflects fluoride excretion after absorption into the plasma, our study assesses fluoride levels in urine at various time points after brushing with either the no-rinse or rinse method. Our study found no significant difference in the amount of fluoride (µg) in urine samples between the no-rinse and rinse groups. In addition, the amount of fluoride in urine from 1 to 6 h after no-rinse brushing is comparable to the amount of baseline urine fluoride (32.54?±?24.11 µg). This indicates minimal fluoride entered the bloodstream after brushing with the no-rinse method in this study. According to previous studies, patients with dental or skeletal fluorosis had urine fluoride levels ranging from 0.7 to 11.4 ppm, which tend to be higher in adults than in children [53, 54]. In contrast to the previous study, the urine fluoride concentrations after no-rinse brushing at all time points in our study ranged from 0.23 to 0.29 ppm, which is far below the urine levels reported from the previous studies. These findings suggest that the single using of the no-rinse method has minimal impact on overall fluoride exposure in the body.

The calculated half-life of fluoride in the no-rinse formula toothpaste was approximately 3 h and 19 min from the no-rinse method and 2 h and 54 min from the rinse method. This is similar to the recorded half-life reported previously in animal studies: fluoride half-life is generally 3–10 h [6]. The renal clearance of fluoride was measured at 14.36 ml/min and 11.85 ml/min in the no-rinse and rinse groups, respectively. These findings align closely with a previous study of renal fluoride clearance in healthy adults, which typically ranges from 12.4 to 71.4 ml/min [55]. Notably, renal clearances calculated from our study were lower than previous findings in children and adolescents which was 30–40 ml/min [56]. The differences in renal clearance observed between our study and previous research may be due to the underlying renal diseases present in the subjects of the prior study. In contrast, our research focused exclusively on healthy young adults. In addition, factors such as urinary pH, urine flow rate, and glomerular filtration rate variance between individuals can also influence the renal clearance of fluoride [56, 57]. In terms of volume of distribution, it was determined to be 4.53 L with the no-rinse method and 3.09 L with the rinse method. The low volume of fluoride distribution suggests minimal distribution into other tissues or fat compartments [58]. However, fluoride remains concentrated within the bloodstream and is cleared effectively by the kidneys. This implies that urine can reflect systemic fluoride levels. Since approximately 50% of fluoride from the bloodstream can be transferred to calcified tissues [6, 59,60,61], our study acknowledges the limitation of providing a partial representation of systemic absorption.

We selected the no-rinse toothpaste to use in this study for its convenience and reduced toxicity to oral tissues. Unlike conventional toothpaste, this formulation excludes sodium lauryl sulfate (SLS), paraben, sugar, plastic microbeads, and alcohol. The absence of SLS, known to be toxic to human gingival fibroblasts [46], makes it more suitable for sensitive oral tissues. SLS in toothpaste can influence fluoride pharmacokinetics by decreasing fluoride uptake to the enamel, disrupting plaque biofilm, and increasing fluoride release from oral reservoirs into saliva [62, 63]. By using the same toothpaste for both methods, we ensured that differences in fluoride absorption were due to the rinsing method alone. For future studies, including a conventional toothpaste with 1000–1500 ppm fluoride as a positive control could help validate our findings.

We acknowledge some confounding variables in our study, such as baseline oral health status and hygiene practices, which could not be fully controlled. While we screened participants for baseline oral health conditions, variability still exists. Additionally, using other dental products such as mouthwash containing fluoride during the study could influence the no-rinse method’s effects. Future research should control for these variables for more precise data.

We also recognize the limitation that our safety data is based on a single brushing with a specific no-rinse toothpaste. Further investigations are needed to evaluate the long-term use of the no-rinse method, compare different toothpaste formulations with conventional ones, and assess the safety of other ingredients in the toothpaste. Our fluoride data may not apply to all age groups, as fluoride accumulation and excretion vary with age [60]. Children’s ability to control fluoride ingestion post-brushing is also our concern, which could increase their risk of dental fluorosis with the no-rinse method. Therefore, further studies involving more diverse populations and various oral conditions, such as periodontitis, are necessary to generalize our safety results. Despite these limitations, our study provides valuable insights into optimizing fluoride toothpaste usage to maximize benefits while minimizing risks.

Overall, our study investigates the safety profile of fluoride, specifically addressing concerns about systemic absorption when brushing without rinsing. This research provides critical information for clinical recommendations and guidelines to enhance oral health benefits while minimizing the risk of fluorosis. To ensure internal validity, we randomly assigned participants into two groups and used a cross-over design, allowing the same participants to test the no-rinse and rinse methods. We standardized variables by starting the experiment 2 h after breakfast, using the same amount (1 g) and type of fluoride toothpaste, and providing low-fluoride food and drinking water to minimize fluoride intake from other sources [64, 65]. These controls strengthened our study’s internal validity. Although our findings from young adults may not apply to all age groups, however, the methodology we developed and validated for assessing fluoride toxicity can be applied to future studies involving children and other populations. Additionally, the brushing technique used in our study follows guidelines recommended by the ADA and BDA, making it relevant to various aspects of oral hygiene care. In summary, minimal fluoride entered the plasma after brushing without rinsing, indicating potential safety in a controlled experiment.