Fluoride

In this study, several lines of evidence are provided to show that Na + , K + -ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as well as increased risk of cancer, metabolic, pulmonary and cardiovascular disease. Evidence is presented to show that fluoride (F) inhibits Na + , K + -ATPase activity by altering biological pathways through modifying the expression of genes and the activity of glycolytic enzymes, metalloenzymes, hormones, proteins, neuropeptides and cytokines, as well as biological interface interactions that rely on the bioavailability of chemical elements magnesium and manganese to modulate ATP and Na + , K + -ATPase enzyme activity. Taken together, the findings of this study provide unprecedented insights into the molecular mechanisms and biological pathways by which F inhibits Na + , K + -ATPase activity and contributes to the etiology and pathophysiology of diseases associated with impairment of this essential enzyme. Moreover, the findings of this study further suggest that there are windows of susceptibility over the life course where chronic F exposure in pregnancy and early infancy may impair Na + , K + -ATPase activity with both short- and long-term implications for disease and inequalities in health. These findings would warrant considerable attention and potential intervention, not to mention additional research on the potential effects of F intake in contributing to chronic disease.

ABSTRACT: Among various types of biological materials used in the assessment of the risk of fluoride (F) exposure, special importance is given to mineralized tissues which reflect long term accumulation of F. The aim of the present paper is to investigate F concentration in dentin of permanent teeth of residents of Poland in relation to environmental factors. The study material consisted of teeth (incisors, canines, premolars, and molars) from 74 residents of Poland, extracted due to medical reasons with the exception of dental caries. Following teeth extraction, the patients were asked to complete a questionnaire concerning date of birth (before or after the cessation of drinking water fluoridation in Poland in 1995), use of F-containing toothpaste in oral hygiene, and consumption of F in certain food products. Determination of F content in teeth was conducted using the potentiometric method. There were significant differences in F concentration in dentin of patients born before or after the year 1995. The use of F-containing toothpaste was found to have a significant effect on F content in dentin. The study did not confirm significant differences between frequency of marine fish and tea consumption and an increase of F content in dentin.

To the Editor I read the article by Perry et al1 with interest. Several other molecular mechanisms and factors may also play a role in how anesthesia may influence cancer outcomes. First, it is important to distinguish the difference between certain fluoridated anesthesia, such as sevoflurane, from their contribution to higher plasma fluoride levels.

Background: After the discovery of fluoride as a caries-preventing agent in the mid-twentieth century, fluoridation of community water has become a widespread intervention, sometimes hailed as a mainstay of modern public health. However, this practice results in elevated fluoride intake and has become controversial for two reasons. First, topical fluoride application in the oral cavity appears to be a more direct and appropriate means of preventing caries. Second, systemic fluoride uptake is suspected of causing adverse effects, in particular neurotoxicity during early development. The latter is supported by experimental neurotoxicity findings and toxicokinetic evidence of fluoride passing into the brain.

Method: An integrated literature review was conducted on fluoride exposure and intellectual disability, with a main focus on studies on children published subsequent to a meta-analysis from 2012.

Results: Fourteen recent cross-sectional studies from endemic areas with naturally high fluoride concentrations in groundwater supported the previous findings of cognitive deficits in children with elevated fluoride exposures. Three recent prospective studies from Mexico and Canada with individual exposure data showed that early-life exposures were negatively associated with children’s performance on cognitive tests. Neurotoxicity appeared to be dose-dependent, and tentative benchmark dose calculations suggest that safe exposures are likely to be below currently accepted or recommended fluoride concentrations in drinking water.

Conclusion: The recent epidemiological results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes.

INTRODUCTION:

Dental fluorosis has been assessed only 3 times in nationally representative oral health surveys in the United States. The first survey was conducted by the National Institute of Dental Research from 1986 to 1987. Subsequently, the National Health and Nutrition Examination Survey (NHANES) conducted fluorosis assessments from 1999 to 2004 and more recently from 2011 to 2012. A large increase in prevalence and severity of fluorosis occurred between the 1986-1987 and 1999-2004 surveys.

OBJECTIVES:

To determine whether the trend of increasing fluorosis continued in the 2011-2012 survey.

METHODS:

We analyzed publicly available data from the 2011-2012 NHANES, calculating fluorosis prevalence and severity using 3 measures: person-level Dean’s Index score, total prevalence of those with Dean’s Index of very mild degree and greater, and Dean’s Community Fluorosis Index. We examined these fluorosis measures by several sociodemographic factors and compared results with the 2 previous surveys. Analyses accounted for the complex design of the surveys to provide nationally representative estimates.

RESULTS:

Large increases in severity and prevalence were found in the 2011-2012 NHANES as compared with the previous surveys, for all sociodemographic categories. For ages 12 to 15 y-an age range displaying fluorosis most clearly-total prevalence increased from 22% to 41% to 65% in the 1986-1987, 1999-2004, and 2011-2012 surveys, respectively. The rate of combined moderate and severe degrees increased the most, from 1.2% to 3.7% to 30.4%. The Community Fluorosis Index increased from 0.44 to 0.67 to 1.47. No clear differences were found in fluorosis rates among categories for most of the sociodemographic variables in the 2011-2012 survey.

CONCLUSION:

Large increases in fluorosis prevalence and severity occurred. We considered several possible spurious explanations for these increases but largely ruled them out based on counterevidence. We suggest several possible real explanations for the increases.

KNOWLEDGE TRANSFER STATEMENT:

The results of this study greatly increase the evidence base indicating that objectionable dental fluorosis has increased in the United States. Dental fluorosis is an undesirable side effect of too much fluoride ingestion during the early years of life. Policy makers and professionals can use the presented evidence to weigh the risks and benefits of water fluoridation and early exposure to fluoridated toothpaste.

Environmental epidemiology is a field replete with controversies, but the intensity of the debate inspired by the fluoridation of municipal water supplies to reduce dental caries is perhaps unrivaled. Governments, as well as individuals, differ in their assessments of water fluoridation as public policy.

Importance:

The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear.

Objective:

To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort.
Design, Setting, and Participants:

This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019.

Exposures:

Maternal urinary fluoride (MUFSG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women.
Main Outcomes and Measures:

Children’s IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score.

Results:

Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUFSG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children’s IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUFSG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUFSG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUFSG was associated with a 4.49-point lower IQ score (95% CI, -8.38 to -0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, -2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, -7.16 to -0.14) in boys and girls.

Conclusions and Relevance:

In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.

BACKGROUND:

Infant consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake. We examined the association between fluoride exposure in infancy and intellectual ability in children who lived in fluoridated or non-fluoridated cities in Canada.

METHODS:

We examined 398 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals cohort who reported drinking tap water. We estimated water fluoride concentration using municipal water reports. We used linear regression to analyze the association between fluoride exposure and IQ scores, measured by the Wechsler Primary and Preschool Scale of Intelligence-III at 3-4 years. We examined whether feeding status (breast-fed versus formula-fed) modified the impact of water fluoride and if fluoride exposure during fetal development attenuated this effect. A second model estimated the association between fluoride intake from formula and child IQ.

RESULTS:

Thirty-eight percent of mother-child dyads lived in fluoridated communities. An increase of 0.5 mg/L in water fluoride concentration (approximately equaling the difference between fluoridated and non-fluoridated regions) corresponded to a 9.3- and 6.2-point decrement in Performance IQ among formula-fed (95% CI: -13.77, -4.76) and breast-fed children (95% CI: -10.45, -1.94). The association between water fluoride concentration and Performance IQ remained significant after controlling for fetal fluoride exposure among formula-fed (B = -7.93, 95% CI: -12.84, -3.01) and breastfed children (B = -6.30, 95% CI: -10.92, -1.68). A 0.5 mg increase in fluoride intake from infant formula corresponded to an 8.8-point decrement in Performance IQ (95% CI: -14.18, -3.34) and this association remained significant after controlling for fetal fluoride exposure (B = -7.62, 95% CI: -13.64, -1.60).

CONCLUSIONS:

Exposure to increasing levels of fluoride in tap water was associated with diminished non-verbal intellectual abilities; the effect was more pronounced among formula-fed children.

Importance:

The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear.

Objective:

To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort.
Design, Setting, and Participants:

This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019.

Exposures:

Maternal urinary fluoride (MUFSG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women.
Main Outcomes and Measures:

Children’s IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score.
Results:

Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUFSG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children’s IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUFSG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUFSG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUFSG was associated with a 4.49-point lower IQ score (95% CI, -8.38 to -0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, -2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, -7.16 to -0.14) in boys and girls.

Conclusions and Relevance:

In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.

Background: Fluoride from environmental sources accumulates preferentially in the pineal gland which produces melatonin, the hormone that regulates the sleep-wake cycle. However, the effects of fluoride on sleep regulation remain unknown. This population-based study examined whether chronic low-level fluoride exposure is associated with sleep patterns and daytime sleepiness among older adolescents in the United States (US).

Method: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2015-2016). We analyzed data from adolescents who had plasma fluoride (n = 473) and water fluoride (n = 419) measures and were not prescribed medication for sleep disorders. Relationships between fluoride exposure and self-reported sleep patterns or daytime sleepiness were examined using survey-weighted linear, binomial logistic or multinomial logistic regression after covariate adjustment. A Holm-Bonferroni correction accounted for multiple comparisons.

Results: The average age of adolescents was 17 years (range = 16-19). Median (IQR) water and plasma fluoride concentrations were 0.27 (0.52) mg/L and 0.29 (0.19) μmol/L respectively. An IQR increase in water fluoride was associated with 1.97 times higher odds of reporting symptoms suggestive of sleep apnea (95% CI: 1.27, 3.05; p = 0.02), a 24 min later bedtime (B = 0.40, 95% CI: 0.10, 0.70; p = 0.05), a 26 min later morning wake time (B = 0.43, 95% CI: 0.13, 0.73; p = 0.04), and among males, a 38% reduction in the odds of reporting snoring (95% CI: 0.45, 0.87, p = 0.03).

Conclusions: Fluoride exposure may contribute to changes in sleep cycle regulation and sleep behaviors among older adolescents in the US. Additional prospective studies are warranted to examine the effects of fluoride on sleep patterns and determine critical windows of vulnerability for potential effects.