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Low-fluoride Dentifrice and Gastrointestinal Fluoride Absorption after Meals

Faculty of Dentistry of Piracicaba, UNICAMP, Av. Limeira 901, 13414-903, Piracicaba, SP, Brazil;

^* corresponding author, jcury{at}fop.unicamp.br

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
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

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
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.

	MATERIALS & METHODS

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
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.

View larger version (25K): [in this window] [in a new window]   Figure 1. Illustration of the experimental design.

	Gastric Content Situations

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

	Dentifrices

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
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.

	Collection and Analysis of Fluoride in Saliva and Urine

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
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 (AUC_saliva) 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.

	Reduction in F Bioavailability

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
The percentage of reduction in F bioavailability caused by the meals and dentifrices was calculated from the area under the curve of salivary data (AUC_saliva). To estimate the effect of meals, we assumed the AUC_saliva 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 AUC_saliva for the 1100 µ dentifrice in a fasting condition estimated as 100% of F absorption.

	Statistical Analysis

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
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 AUC_saliva 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 AUC_saliva 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%.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
For the 3 variables (Cmax, AUC_saliva, 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). With the variable dentifrice, when the non-fluoridated one was ingested, the values of Cmax, AUC_saliva, and F in urine did not differ statistically (p > 0.05), regardless of the gastric content condition evaluated (Table), showing that the negative control used was appropriate. When the fluoride dentifrices were evaluated, the differences among the 3 gastric conditions for Cmax and AUC_saliva were significant (p < 0.05), and the lowest values were found when they were ingested after lunch (Table). With regard to F in urine, the only statistically significant difference was for intake of the conventional dentifrice after lunch compared with the fasting condition (Table).

The time for maximum salivary concentration (Tmax) was around 45 min for all groups ingesting F dentifrices (Fig. 2).

View larger version (17K): [in this window] [in a new window]   Figure 2. Mean and SD of salivary F concentration after the ingestion of the dentifrices under different gastric content situations (for n of each treatment, refer to Table).

View larger version (38K): [in this window] [in a new window]   Figure 3. Percent bioavailability of F dentifrices ingested in different gastric content situations. (a) Reduction in the F bioavailability of the 1100-µg-F/g dentifrice for ingestion after the meals. (b) Same as (a) for the 550-µg-F/g dentifrice. (c) Overall reduction in F bioavailability, from both meals and dentifrices, with the absorption of the 1100-µg-F/g dentifrice ingested on fasting considered as 100%.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

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 (AUC_saliva) when compared with that caused by the conventional dentifrice, regardless of the gastric content (Table), reducing F bioavailability to around 59%. Indeed, a highly significant correlation was observed between the amount of F ingested and that absorbed (Appendix Fig., a). These results are expected, because F shows ready bioavailability from dentifrices, for those containing either NaF or MFP (Ekstrand and Ehrnebo, 1980; Roldi and Cury, 1986; Drummond et al., 1990). Also, the F dentifrices used were silica-based, and did not contain Ca or Al (as an abrasive), which could interfere with F absorption (Whitford, 1994).

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), confirming results obtained with other foods (Ekstrand and Ehrnebo, 1979; Spak et al., 1982; Trautner and Einwag, 1989). The reduction in bioavailability from salivary data was 22–28% when dentifrices were ingested after breakfast, and 35–39% for ingestion after lunch (Figs. 3a, 3b).

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.

	ACKNOWLEDGMENTS

 
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 March 29, 2004; Last revision July 28, 2005; Accepted August 28, 2005

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS Gastric Content Situations Dentifrices Collection and Analysis of... Reduction in F Bioavailability Statistical Analysis RESULTS DISCUSSION REFERENCES

 
Ammari AB, Bloch-Zupan A, Ashley PF (2003). Systematic review of studies comparing the anti-caries efficacy of children’s toothpaste containing 600 ppm of fluoride or less with high fluoride toothpastes of 1,000 ppm or above. Caries Res 37:85–92.[ISI][Medline]

Box GEP, Hunter WG, Hunter JS (1978). Statistics for experimenters: an introduction to design, data analysis and model building. New York: John Wiley & Sons Inc.

Burt BA (1992). The changing patterns of systemic fluoride intake. J Dent Res 71:1228–1237.[Abstract/Free Full Text]

Cangussu MC, Narvai PC, Castellanos Fernandez R, Djehizian V (2002). Dental fluorosis in Brazil: a critical review (in Portuguese). Cad Saude Publica 18:7–15.

Clarkson J, Hardwick K, Barmes D, Richardson LM (2000). International collaborative research on fluoride. J Dent Res 79:893–904.[Free Full Text]

de Menezes LM, de Sousa MdaL, Rodrigues LK, Cury JA (2002). Self-perception of fluorosis due to fluoride exposure to drinking water and dentifrice (in Portuguese). Rev Saúde Publica 36:752–754.[ISI][Medline]

Drummond BK, Curzon MEJ, Strong M (1990). Estimation of fluoride absorption from swallowed fluoride toothpastes. Caries Res 24:211–215.[ISI][Medline]

Ekstrand J (1977). Fluoride concentrations in saliva after single oral doses and their relation to plasma fluoride. Scand J Dent Res 85:16–17.[ISI][Medline]

Ekstrand J, Ehrnebo M (1979). Influence of milk products on fluoride bioavailability in man. Eur J Clin Pharmacol 16:211–215.[ISI][Medline]

Ekstrand J, Ehrnebo M (1980). Absorption of fluoride from fluoride dentifrices. Caries Res 14:96–102.[ISI][Medline]

Ekstrand J, Spak CJ, Vogel G (1990). Pharmacokinetics of fluoride in man and its clinical relevance. J Dent Res 69(Spec Iss):550–555, discussion 556–557.

Fejerskov O, Baelum V, Richards A (1996). Dose-response and dental fluorosis. In: Fluoride in dentistry. Ekstrand J, Burt BA, editors. Copenhagen: Munksgaard, pp. 153–166.

Horowitz HS (1992). The need for toothpastes with lower than conventional fluoride concentrations for preschool-aged children. J Public Health Dent 52:216–221.[ISI][Medline]

Narvai PC, Frazão P, Castellanos RA (1999). Decline in dental caries experience in permanent teeth of the Brazilian schoolchildren at the end of the 20th century (in Portuguese). Odontol Soc 1:25–29.

Oliveby A, Lagerlöf F, Ekstrand J, Dawes C (1989). Studies on fluoride excretion in human whole saliva and its relation to flow rate and plasma fluoride levels. Caries Res 23:243–246.[ISI][Medline]

Paiva SM, Lima YB, Cury JA (2003). Fluoride intake by Brazilian children from two communities with fluoridated water. Community Dent Oral Epidemiol 31:184–191.[ISI][Medline]

Pang DT, Vann WF Jr (1992). The use of fluoride-containing toothpastes in young children: the scientific evidence for recommending a small quantity. Pediatr Dent 14:384–387.[Medline]

Rojas-Sanchez F, Kelly SA, Drake KM, Eckert GJ, Stookey GK, Dunipace AJ (1999). Fluoride intake from foods, beverages and dentifrice by young children in communities with negligibly and optimally fluoridated water: a pilot study. Community Dent Oral Epidemiol 27:288–297.[ISI][Medline]

Roldi CR, Cury JA (1986). Fluoride metabolism after ingestion of dentifrice (in Portuguese). Rev Gaúcha Odontol 34:425–427.

Rozier RG (1999). The prevalence and severity of enamel fluorosis in North American children. J Public Health Dent 59:239–246.[ISI][Medline]

Seppä L, Salmenkivi S, Hausen H (1997). Salivary fluoride concentration in adults after different fluoride procedures. Acta Odontol Scand 55:84–87.[ISI][Medline]

Spak CJ, Ekstrand J, Zylberstein D (1982). Bioavailability of fluoride added by baby formula and milk. Caries Res 16:249–256.[ISI][Medline]

Trautner K, Einwag J (1989). Influence of milk and food on fluoride bioavailability from NaF and Na2FPO3 in man. J Dent Res 68:72–77.[Abstract/Free Full Text]

Warren JJ, Levy SM (1999). A review of fluoride dentifrice related to dental fluorosis. Pediatr Dent 21:265–271.[Medline]

Whitford GM (1994). Intake and metabolism of fluoride. Adv Dent Res 8:5–14.[Abstract]

Whitford GM, Thomas JE, Adair SM (1999). Fluoride in whole saliva, parotid ductal saliva and plasma in children. Arch Oral Biol 44:785–788.[ISI][Medline]

Zero DT, Raubertas RF, Fu J, Pedersen AM, Hayes AL, Featherstone JD (1992). Fluoride concentrations in plaque, whole saliva, and ductal saliva after application of home-use topical fluorides. J Dent Res 71:1768–1775.[Abstract/Free Full Text]

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