Fluoride

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.

Pursuant to 21 C.F.R. § 10.25(a)(2) and 21 C.F.R. § 10.30, the Fluoride Action Network and International Academy of Oral Medicine & Toxicology (collectively, “Petitioners”), respectfully submit this Petition to request that the Commissioner of the U.S. Food & Drug Administration (FDA) exercise its authority under the Food, Drug & Cosmetic Act to take action to ensure an expedited removal from the market of unapproved, unsafe, unnecessary, and ineffective sodium fluoride-containing drops, tablets, and lozenges sold for the intended purpose of caries prevention (i.e., “fluoride supplements”).

OBJECTIVE: To conduct a systematic review of randomised trials assessing the association between personal oral hygiene and dental caries in the absence of the confounding effects of fluoride.

Most of the studies included in this systematic review are more than 20 years old. As such, the reporting of the trials often lacked meth-odological detail necessary to produce high quality recommendations.  When new trials on fluoride mouthrinses for caries control are conducted, these should focus on direct comparisons between dif-ferent fluoride mouthrinse features or comparisons of fluoride rinses against other preventive strategies, such as tooth sealants. Since there is also little evidence related to adverse effects of flu-oride mouthrinses, additional studies to quantify and describe tooth staining, mucosal irritation, and acute toxicity are warranted.

The elevated fluoride from drinking water impacts on T3, T4 and TSH hormones. The aim was study impacts of drinking water fluoride on T3, T4 and TSH hormones inYGA (Yazd Greater Area). In this case- control study 198 cases and 213 controls were selected. Fluoride was determined by the SPADNS Colorimetric Method. T3, T4 and TSH hormones tested in the Yazd central laboratory by RIA (Radio Immuno Assay) method. The average amount of TSH and T3 hormones based on the levels of fluoride in two concentration levels 0-0.29 and 0.3-0.5 (mg/L) was statistically significant (P = 0.001 for controls and P = 0.001 for cases). In multivariate regression logistic analysis, independent variable associated with Hypothyroidism were: gender (odds ratio: 2.5, CI 95%: 1.6-3.9), family history of thyroid disease (odds ratio: 2.7, CI 95%: 1.6-4.6), exercise (odds ratio: 5.34, CI 95%: 3.2-9), Diabetes (odds ratio: 3.7, CI 95%: 1.7-8), Hypertension (odds ratio: 3.2, CI 95%: 1.3-8.2), water consumption (odds ratio: 4, CI 95%: 1.2-14). It was found that fluoride has impacts on TSH, T3 hormones even in the standard concentration of less than 0.5 mg/L. Application of standard household water purification devices was recommended for hypothyroidism.

Purpose: Excessive fluoride ingestion has been associated with dental fluorosis. The purpose of this study was to determine if there was a difference in dental fluorosis prevalence comparing National Health and Nutrition Examination Survey (NHANES) trend data for adolescents, aged 16 and 17 years, when compared to data collected in 2001-2002 to data from 2011-2012.Methods: The sample included 875 participants. Data analyses included Chi square tests and logistic regressions. The data were from a nationally representative survey by calibrated dental examiners using the modified Dean’s fluorosis classification system. The data analysis of the prevalence of fluorosis severity level was dichotomized to very mild/above vs. normal/questionable.Results: In 2001-2002, the weighted percentage prevalence of the denoted dental fluorosis categories were: 49.8% normal (i.e., unaffected), 20.5% questionable, and 29.7% very mild and above. In 2011-2012, the weighted percentage prevalence categories were: 31.2% normal, 7.5% questionable, and 61.3% very mild and above. When comparing years 2001-2002 with the years 2011-2012, the prevalence of very mild and above fluorosis increased by 31.6% (P <.0001) for the 2011-2012 group. In adjusted logistic regression, participants from the years 2011-2012 were more likely to have very mild and above dental fluorosis than participants in 2001-2002 as compared with normal/questionable fluorosis (Adjusted odds ratio= 3.85; 95% confidence interval= 2.20, 6.72; P <.0001).Conclusion: There was a difference of 31.6% in dental fluorosis prevalence between 2012-2011 when compared to data from 2002-2001 in adolescents aged 16 and 17 years. The continued increase in fluorosis rates in the U.S. indicates that additional measures need to be implemented to reduce its prevalence.

In this opinion article, FV Zohoori and A. Maguire highlight the importance of controlling
systemic fluoride intake from food and drink in early childhood to minimise risk of dental
fluorosis whilst maximizing caries prevention.

BACKGROUND:
Fluoride exposure has the potential to disrupt thyroid functioning, though adequate iodine intake may mitigate this effect. This is the first population-based study to examine the impact of chronic low-level fluoride exposure on thyroid function, while considering iodine status. The objective of this study was to determine whether urinary iodine status modifies the effect of fluoride exposure on thyroid stimulating hormone (TSH) levels.

METHODS:
This cross-sectional study utilized weighted population-based data from Cycle 3 (2012-2013) of the Canadian Health Measures Survey (CHMS). Information was collected via a home interview and a visit to a mobile examination centre. The weighted sample represented 6,914,124 adults in Canada aged 18-79 who were not taking any thyroid-related medication. Urinary fluoride concentrations were measured in spot samples using an ion selective electrode and adjusted for specific gravity (UFSG). Serum TSH levels provided a measure of thyroid function. Multivariable regression analyses examined the relationship between UFSG and TSH, controlling for covariates.

RESULTS:
Approximately 17.8% of participants fell in the moderately-to-severely iodine deficient range. The mean (SD) age of the sample was 46.5 (15.6) years and the median UFSG concentration was 0.74 mg/L. Among iodine deficient adults, a 1 mg/L increase in UFSG was associated with a 0.35 mIU/L increase in TSH [95% CI: 0.06, 0.64; p = 0.01, one-tailed].

CONCLUSIONS:
Adults living in Canada who have moderate-to-severe iodine deficiencies and higher levels of urinary fluoride may be at an increased risk for underactive thyroid gland activity.