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Low-fluoride Dentifrice and Gastrointestinal Fluoride Absorption after MealsFaculty of Dentistry of Piracicaba, UNICAMP, Av. Limeira 901, 13414-903, Piracicaba, SP, Brazil; Correspondence: * corresponding author, jcury{at}fop.unicamp.br
A low-fluoride (F) dentifrice has been recommended to reduce the risk of dental fluorosis, but its anti-caries efficacy is questionable compared with that of conventional dentrifices (1000–1100 µg F/g). The tested hypothesis was that conventional dentifrices might be safe if used soon after meals, since food interferes with F absorption. In a crossover, double-blind study, 11 volunteers ingested a dentifrice slurry containing 0 (placebo), 550 (low F), or 1100 µg F/g in 3 gastric content situations: on fasting, or 15 min after breakfast or lunch. F was analyzed in saliva and 24-hour urine samples. The conventional dentifrice ingested after lunch resulted in only 10% higher F absorption than the low-F ingested on fasting. Analysis of the data suggests that the risk of fluorosis could be reduced by the use of either a low-F dentifrice or a conventional dentifrice, if toothbrushing occurred soon after meals.
Key Words: fluoride • dentifrice • absorption • saliva • food
Fluoridated (F) dentifrices have been considered an important reason for the decline in dental caries observed in both developed and developing countries at the end of the last century (Narvai et al., 1999; Clarkson et al., 2000). However, they are also considered a risk factor with respect to dental fluorosis (Warren and Levy, 1999), and there is evidence that dental fluorosis is increasing in developed and developing countries, regardless of exposure to water fluoridation (Rozier, 1999; Cangussu et al., 2002). It has been estimated that children at risk for dental fluorosis are subjected—from 1000- to 1100-µg F/g dentifrices alone—to a dose close to the estimated upper limit for safe F intake (Rojas-Sanchez et al., 1999; Paiva et al., 2003). A low-F dentifrice has been suggested as an alternative to reduce this risk (Horowitz, 1992). However, the anti-caries efficacy of such dentifrices is generally believed to be reduced (Ammari et al., 2003), and there are no data in the literature comparing F intake from the low-F dentifrice with that from a conventional 1000-to 1100-µg-F/g dentifrice. Furthermore, the prevalence of dental fluorosis in populations using conventional F dentifrices is lower than that expected on the basis of F intake data (Fejerskov et al., 1996). This could be explained by the timing of toothbrushing in relation to mealtimes, and by the composition of meals, since F absorption depends on the presence of food in the stomach (Ekstrand and Ehrnebo, 1979). Therefore, if brushing with a dentifrice containing 1100 µg F/g were done soon after meals, F absorption would be reduced, and the risk of dental fluorosis could be similar to that from the use of a 550-µg-F/g dentifrice in a fasting condition, but this has not been explored. Thus, the aim of this study was to evaluate the combined effect of meals and a low-F-concentration dentifrice on the reduction of F absorption, testing the hypothesis that, if a conventional F dentifrice were used soon after meals, it would be as safe as a low-F dentifrice used in a fasting situation, in terms of risk of dental fluorosis.
Experimental Design This double-blind, crossover study was conducted according to the Brazilian Resolution no. 196, National Health Council, Health Ministry, Brasília, DF, 10/10/1996, and the volunteers had previously signed an informed, written consent.
Eleven healthy volunteers, six females and five males, aged 17 to 20 yrs, drinking optimally fluoridated water (0.7 ppm), ingested dentifrices with different F concentrations (0, 550, and 1100 µg F/g), in 3 different gastric content situations (fasting, after breakfast, and after lunch). The number of volunteers was established after a pilot study, to reach a 90% estimated power. The study consisted of 9 phases, with a wash-out period of 7 days between them. Volunteers were divided into three groups with different meals/dentifrices in each phase, until all combinations of meal/dentifrice had been used by each volunteer. The order of the treatments was chosen at random. During a seven-day lead-in period, and throughout the experiment, volunteers brushed their teeth with a non-F dentifrice and were instructed to avoid F rinses or gels and F-rich foods, such as tea and seafood. Standard breakfasts and lunches, as usually eaten in Brazil, were prepared. Volunteers ingested a slurry (45 mg/kg body weight) of the assigned dentifrice without brushing 15 min after the meal, a critical time with respect to the effect of food on F bioavailability (Ekstrand et al., 1990). Unstimulated whole saliva, as an indicator of plasma F concentration (Oliveby et al., 1989), was collected for 3 hrs. All urine produced during 24 hrs before (baseline) and 24 hrs after the ingestion of the dentifrice was collected. F concentration in saliva and urine was determined by the use of an ion-selective electrode. The experimental design is illustrated in Fig. 1
After fasting overnight, volunteers were given the assigned meal (none, breakfast, or lunch), according to the experimental design. Breakfast consisted of a small French bread roll, 10 g of margarine, and 200 mL of coffee with milk (1:3); lunch consisted of 127.7 g of rice, 125.0 g of beans, 163.8 g of meat with potatoes, and 58.3 g of lettuce and tomato salad. The breakfast and lunch menus were prepared according to meals usually eaten in Brazil. To ensure that all food was eaten, we standardized the amounts of food offered for lunch based on a meal previously offered to the volunteers.
Dentifrices were prepared by Colgate-Palmolive (São Bernardo do Campo, SP, Brazil). They were silica-based, strawberry-flavored, and contained 0, 550, or 1100 µg F/g, as NaF. They were coded so that neither volunteers nor the investigators knew their F content. Fifteen min after the meals, a slurry of the assigned dentifrice (containing 45 mg dentifrice per kg body weight), freshly prepared in 10 mL of distilled and de-ionized water (DDW), was ingested by the volunteers. After ingestion, volunteers rinsed their mouths with 30 mL of DDW, which they swallowed. The amount of dentifrice ingested by volunteers was calculated on the basis of a child weighing 13.5 kg, brushing 2 times a day, and ingesting about 0.3 g of dentifrice per brushing (Paiva et al., 2003), and corresponded to 0, 24.8, and 49.5 µg F/kg body weight, respectively, for dentifrices with 0, 550, and 1100 µg F/g.
Unstimulated whole saliva was collected at time zero, and at 0.25, 0.50, 0.75, 1, 2, and 3 hrs after ingestion of the dentifrice, centrifuged at 16,000 g for 1 min, and frozen until F analysis. All urine, 24 hrs before and 24 hrs after the ingestion of dentifrices, was collected by the volunteers in separate plastic receptacles. The total volumes were measured, and aliquots of 10 mL were centrifuged at 3000 g for 10 min and frozen until analysis. F was analyzed in duplicate aliquots of saliva and urine, buffered with TISAB II, with an ion-selective electrode (Orion 96-09) and ion analyzer (Orion EA-940), previously calibrated with standard F solutions (Orion 940907, Boston, MA, USA). The analyses were validated according to internal standards, and a coefficient of variation lower than 3% was considered as acceptable. F concentration in saliva was plotted vs. time, and maximum concentration (Cmax) and time for maximum concentration (Tmax) were determined. The area under the salivary F concentration vs. time curve (AUCsaliva) was calculated up to 3 hrs after ingestion, by the program PK Solutions (Summit Research Services, Montrose, CO, USA). F in urine represents the difference of F excreted in urine 24 hrs after the ingestion of the dentifrices minus the baseline measurement.
The percentage of reduction in F bioavailability caused by the meals and dentifrices was calculated from the area under the curve of salivary data (AUCsaliva). To estimate the effect of meals, we assumed the AUCsaliva in the fasting condition to represent 100% of F absorption, for either the conventional or the low-F dentifrice; the effect of the combination meals-dentifrice was estimated with the g F/g AUCsaliva for the 1100 µ dentifrice in a fasting condition estimated as 100% of F absorption.
A factorial 3 x 3 (3 levels of gastric content and 3 levels of dentifrices) was considered for the statistical analysis of data, and the volunteer was considered as a statistical block. The assumptions of equality of variance and normality of error were checked for all the response variables tested, and those that did not satisfy were transformed (Box et al. 1978); values of Cmax and AUCsaliva were transformed to the square root, and values of F excreted in urine were transformed to the power of 1.4, after 1 was added to the data to avoid negative values. These data were analyzed by analysis of variance (ANOVA), which was followed by the Tukey test. The relationship between the amount of F ingested and either AUCsaliva or F excreted was tested by Spearman’s coefficient of correlation, but the data were used without being transformed. All analyses were performed with the SAS System 8.01 software (SAS Institute Inc., Cary, NC, USA), and the significance limit was set at 5%.
For the 3 variables (Cmax, AUCsaliva, and F excreted), there was a statistically significant interaction (p < 0.05) between the factors gastric content and dentifrice.
The differences among the dentifrices, for each gastric content condition evaluated, were all significant (p < 0.05; Table
For the 3 gastric content conditions, the correlation between the amount of F ingested from dentifrices and either the AUCsaliva or the amount of F excreted in the urine was statistically significant (p < 0.0001). For the correlations between F ingested and AUCsaliva, values of r were 0.93, 0.90, and 0.90, respectively, for fasting, breakfast, and lunch. Correlations between F ingested and excreted in the urine presented r values of 0.88, 0.86, and 0.83, for fasting, breakfast, and lunch, respectively (Appendix Fig.).
The time for maximum salivary concentration (Tmax) was around 45 min for all groups ingesting F dentifrices (Fig. 2
Figs. 3a and 3b  show the reduction in F bioavailability caused by meals for the conventional or the low-F dentifrice. Breakfast itself reduced F absorption to 78% and 71% for the 550- and 1100-µg-F/g dentifrices, respectively. Lunch reduced F absorption to 65% and 61% for the 550- and 1100-µg-F/g dentifrices, respectively. For the effect of the combination meals-dentifrice (Fig. 3c), assuming the ingestion of the conventional dentifrice on fasting as 100% bioavailability, we observed a gradual decrease in F bioavailability, in the following order: conventional dentifrice after breakfast (71%), conventional dentifrice after lunch (61%), low-F dentifrice on fasting (56%), low-F dentifrice after breakfast (43%), and low-F dentifrice after lunch (36%).
Although parotid ductal saliva is a more appropriate biomarker of fluoride exposure than whole saliva (Whitford et al., 1999), whole saliva was used as a F bioavailability indicator, since there is good correlation between plasma F and either F concentration in parotid saliva (Ekstrand, 1977) or whole saliva (Oliveby et al., 1989). Furthermore, the reliability and validity of whole saliva, for the evaluation of F absorption after either the ingestion of dentifrices (Roldi and Cury, 1986; Drummond et al., 1990) or the use of F products (Zero et al., 1992; Seppä et al., 1997), have been demonstrated. In addition, the high correlations found in this study between the amounts of F ingested and the AUC of salivary F concentration (Appendix Fig., a) also support the use of whole saliva as a F bioavailability indicator. Furthermore, the observed Tmax for salivary F concentration, around 45 min, shows the lack of contamination of the saliva samples with the toothpastes ingested. Similar Tmax values were reported by Roldi and Cury (1986), for salivary levels after the ingestion of dentifrices on fasting, and by Ekstrand et al.(1990), for plasma F levels when dentifrices were ingested 15 min after breakfast. Although a delay in maximum plasma F concentration has been described (Trautner and Einwag, 1989), this occurred when NaF was ingested concurrently with breakfast, but in the present study the dentifrices were ingested 15 min after meals.
The results showed that the low-F-concentration dentifrice caused a lower F absorption (AUCsaliva) when compared with that caused by the conventional dentifrice, regardless of the gastric content (Table
When one considers the typical Brazilian meals ingested, the findings show that ingesting toothpaste 15 min after either breakfast or lunch reduces F absorption (Table F dentifrices are considered a risk factor for dental fluorosis (Warren and Levy, 1999), but questions about the timing of brushing after meals have not been raised. Thus, the reduction in F absorption by Brazilian foods from swallowed dentifrices may partially explain the apparent lack of relationship between F intake data and the expected dental fluorosis prevalence (Fejerskov et al., 1996). In fact, the well-being of children from Piracicaba, who ingest the typical foods evaluated in this study and regularly brush their teeth with F dentifrices, was shown not to be affected when self-perception of fluorosis was evaluated (de Menezes et al., 2002). Although the mean F intake of these children is 0.090 mg F/kg/day, when one considers the combined intake from diet and dentifrice (Paiva et al., 2003), if brushing had occurred after lunch, the total F dose estimated would be reduced to around 0.071 mg F/kg/day, much closer to the upper limit for safe fluoride intake with regard to dental fluorosis risk (Burt, 1992). It seems that, in addition to the recommendation to use a small amount of dentifrice (Pang and Vann, 1992), the habit of brushing immediately after meals would reduce the risk of dental fluorosis, since any inadvertently swallowed F would not be totally absorbed. However, the effect of other kinds of foods on F absorption should be evaluated. In conclusion, with regard to the risks of dental fluorosis, analysis of the data suggests that if the conventional dentifrice containing 1000 to 1100 µg F/g were used soon after meals, it would be as safe as the low-F-concentration dentifrice used in fasting conditions.
The authors thank Mariza J. Soares, Waldomiro V. Filho, José Gregório, and Ademir Mariano for their valuable technical assistance. The first author, authorized by the State University of Campinas, was a scientific consultant to Kolynos do Brasil (now Colgate-Palmolive) during the time this study was conducted. This study was supported by CAPES (Brazilian Coordination of Training of Higher Education Graduate). This paper is based on a thesis submitted by the second author to the Faculty of Dentistry of Piracicaba, University of Campinas, in partial fulfillment of the requirements for a MS degree in Dentistry (concentration in Pharmacology). Received for publication March 29, 2004. Revision received July 28, 2005. Accepted for publication August 28, 2005.
Journal of Dental Research, Vol. 84, No. 12,
1133-1137 (2005) This article has been cited by other articles:
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