Waugh DT. Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health. Int J Environ Res Public Health. 2019 Mar 26;16(6). pii: E1086. doi: 10.3390/ijerph16061086.
The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and accumulation of iodine and its activity is crucial for the development of the central nervous system and disease prevention. Since the discovery of NIS in 1996, research has further shown that NIS functionality and iodine transport is dependent on the activity of the sodium potassium activated adenosine 5′-triphosphatase pump (Na+, K+-ATPase). In this article, I review the molecular mechanisms by which F inhibits NIS expression and functionality which in turn contributes to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders. I discuss how NIS expression and activity is inhibited by thyroglobulin (Tg), tumour necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β), interferon-γ (IFN-γ), insulin like growth factor 1 (IGF-1) and phosphoinositide 3-kinase (PI3K) and how fluoride upregulates expression and activity of these biomarkers. I further describe the crucial role of prolactin and megalin in regulation of NIS expression and iodine homeostasis and the effect of fluoride in down regulating prolactin and megalin expression. Among many other issues, I discuss the potential conflict between public health policies such as water fluoridation and its contribution to iodine deficiency, neurodevelopmental and pathological disorders. Further studies are warranted to examine these associations.
Moore D, Goodwin M, Pretty IA. Long-term variability in artificially and naturally fluoridated water supplies in England. Community dentistry and oral epidemiology, 2019 Oct 18. doi: 10.1111/cdoe.12502
OBJECTIVES: To understand the potential impact of exposure misclassification on water fluoridation studies in England, this paper aims to describe the long-term variation in water fluoride concentrations in both artificially and naturally fluoridated water supplies.
METHODS: Water fluoridation dose monitoring data were requested from all five English public water suppliers who artificially fluoridate their water, as well as from one water company that supplies naturally fluoridated water. Descriptive statistics were calculated, including annual means, standard deviations, minimum-maximum and absolute and relative frequencies.
RESULTS: Data were made available by two of the five English water companies who supply artificially fluoridated water and one water company that supplies naturally fluoridated water (40 398 individual samples). The data for fluoridated water spanned 18-35 years, whilst the data on naturally fluoridated water spanned 14 years. The artificially fluoridated samples showed wide variation in fluoride dose control, both between different water treatment works and over time. Mean fluoride concentrations in the artificially fluoridated supplies ranged from 0.53 (SD 0.47) to 0.93 (SD 0.22) mg F/L and were within the optimal range of 0.7-1.0 mg F/L in 27.7%-77.8% of samples. The naturally fluoridated supplies had a higher mean fluoride concentration of 1.06 (SD 0.18) and 1.15 (SD 0.16) mg F/L than the artificially fluoridated supplies, with lower variation over time. The naturally fluoridated supplies were above the optimal range in 75.5% and 53% of samples.
CONCLUSIONS: Assumptions that populations living in areas with a water fluoridation scheme have received optimally fluoridated water (0.7-1.0 mg F/L) are invalid. To support future research endeavours, as well as to provide ‘external control’ and facilitation of optimal dosing, it is recommended that a quarterly record of water fluoride concentrations (mean, standard deviation and minimum and maximum) are made available for every water supply in England, in a format that can be mapped against residential postcodes.
Christine Till, Rivka Green, John G. Grundy, Richard Hornung, Raichel Neufeld, E. Angeles Martinez-Mier, Pierre Ayotte, Gina Buckle, and Bruce Lanphear.
Community Water Fluoridation and Urinary Fluoride Concentrations in a National Sample of Pregnant Women in Canada. Environmental Health Perspectives Vol. 126, No. 10. https://doi.org/10.1289/EHP3546
Background: Fluoride exposures have not been established for pregnant women who live in regions with and without community water fluoridation.
Objective: Our aim was to measure urinary fluoride levels during pregnancy. We also assessed the contribution of drinking-water and tea consumption habits to maternal urinary fluoride (MUF) concentrations and evaluated the impact of various dilution correction standards, including adjustment for urinary creatinine and specific gravity (SG).
Methods: We measured MUF concentrations in spot samples collected in each trimester of pregnancy from 1,566 pregnant women in the Maternal–Infant Research on Environmental Chemicals cohort. We calculated intraclass correlation coefficients (ICCs) to assess variability in MUF concentrations across pregnancy. We used regression analyses to estimate associations between MUF levels, tea consumption, and water fluoride concentrations as measured by water treatment plants.
Results: Creatinine-adjusted MUF values (mean±SD; milligrams per liter) were almost two times higher for pregnant women living in fluoridated regions (0.87± 0.50) compared with nonfluoridated regions (0.46±0.34; p<0.001). MUF values tended to increase over the course of pregnancy using both unadjusted values and adjusted values. Reproducibility of the unadjusted and adjusted MUF values was modest (ICC range=0.37–0.40). The municipal water fluoride level was positively associated with creatinine-adjusted MUF (B=0.52, 95% CI: 0.46, 0.57), accounting for 24% of the variance after controlling for covariates. Higher MUF concentrations correlated with numbers of cups of black (r=0.31–0.32) but not green tea (r equals 0.04 to 0.06"r=0.91) and were interchangeable in models examining predictors of MUF.
Conclusion: Community water fluoridation is a major source of fluoride exposure for pregnant women living in Canada. Urinary dilution correction with creatinine and SG were shown to be interchangeable for our sample of pregnant women.
Aoun A, Darwiche F, Al Hayek S, Doumit J. The Fluoride Debate: The Pros and Cons of Fluoridation. Preventive nutrition and food science. 2018 Sep;23(3):171-180. doi: 10.3746/pnf.2018.23.3.171.
Fluoride is one of the most abundant elements found in nature. Water is the major dietary source of fluoride. The only known association with low fluoride intake is the risk of dental caries. Initially, fluoride was considered beneficial when given systemically during tooth development, but later research has shown the importance and the advantages of its topical effects in the prevention or treatment of dental caries and tooth decay. Water fluoridation was once heralded as one of the best public health achievements in the twentieth century. Since this practice is not feasible or cost effective in many regions, especially rural areas, researchers and policy makers have explored other methods of introducing fluoride to the general population such as adding fluoride to milk and table salt. Lately, major concerns about excessive fluoride intake and related toxicity were raised worldwide, leading several countries to ban fluoridation. Health-care professionals and the public need guidance regarding the debate around fluoridation. This paper reviews the different aspects of fluoridation, their effectiveness in dental caries prevention and their risks. It was performed in the PubMed and the Google Scholar databases in January 2018 without limitation as to the publication period.
Till C, Green R, Grundy JG, Hornung R, Neufeld R, Martinez-Mier EA, Ayotte P, Muckle G, Lanphear B. Community Water Fluoridation and Urinary Fluoride Concentrations in a National Sample of Pregnant Women in Canada. Environmental health perspectives. 2018 Oct;126(10):107001. doi: 10.1289/EHP3546.
BACKGROUND: Fluoride exposures have not been established for pregnant women who live in regions with and without community water fluoridation.
OBJECTIVE: Our aim was to measure urinary fluoride levels during pregnancy. We also assessed the contribution of drinking-water and tea consumption habits to maternal urinary fluoride (MUF) concentrations and evaluated the impact of various dilution correction standards, including adjustment for urinary creatinine and specific gravity (SG).
METHODS: We measured MUF concentrations in spot samples collected in each trimester of pregnancy from 1,566 pregnant women in the Maternal-Infant Research on Environmental Chemicals cohort. We calculated intraclass correlation coefficients (ICCs) to assess variability in MUF concentrations across pregnancy. We used regression analyses to estimate associations between MUF levels, tea consumption, and water fluoride concentrations as measured by water treatment plants.
RESULTS: Creatinine-adjusted MUF values were almost two times higher for pregnant women living in fluoridated regions compared with nonfluoridated regions. MUF values tended to increase over the course of pregnancy using both unadjusted values and adjusted values. Reproducibility of the unadjusted and adjusted MUF values was modest . The municipal water fluoride level was positively associated with creatinine-adjusted MUF, accounting for 24% of the variance after controlling for covariates. Higher MUF concentrations correlated with numbers of cups of black but not green tea. Urinary creatinine and SG correction methods were highly correlated and were interchangeable in models examining predictors of MUF.
CONCLUSION: Community water fluoridation is a major source of fluoride exposure for pregnant women living in Canada. Urinary dilution correction with creatinine and SG were shown to be interchangeable for our sample of pregnant women.
Spencer AJ, Do LG, Ha DH. Contemporary evidence on the effectiveness of water fluoridation in the prevention of childhood caries. Community Dent Oral Epidemiol. 2018 Aug;46(4):407-415. doi: 10.1111/cdoe.12384.
BACKGROUND: Water fluoridation’s effectiveness has been reaffirmed by systematic reviews. However, most of the included nonrandomised controlled before and after studies were conducted pre-1975. Opportunity for such studies is limited in a steady state of community fluoridation programmes. As an alternative for evidence to support or refute the effectiveness of water fluoridation, this study used data from a recent national child oral health study to examine associations between lifetime exposure to fluoridated water (%LEFW) and childhood caries.
METHODS: A population-based study of child oral health in Australia was conducted in 2012-2014, using complex sampling and weighting procedures. Parents provided detailed household information and children underwent oral epidemiological examination by trained examiners. Residential history from birth was used to calculate %LEFW. Caries prevalence (dmfs/DMFS>0) and experience (dmfs/DMFS) in both primary (age 5-8) and permanent dentitions (age 9-14) were estimated. Socioeconomic factors that were significantly different by %LEFW were then used as covariates in multivariable log-Poisson regression models for each caries outcome by %LEFW.
RESULTS: A total of 24 664 children had complete data. Caries prevalence and experience were higher among 5-8-year-old children with lower %LEFW (46.9%; 4.27 surfaces) than those with 100%LEFW (31.5%; 1.98 surfaces) and for the 9-14-year-old children with lower %LEFW (37.0%; 1.34 surfaces) than those with 100%LEFW (25.0%; 0.67 surfaces). In the multivariable models, the prevalence ratios for primary and permanent caries were significant for the two lower exposure groups against the 100%LEFW group. Similarly, the mean ratios for primary dmfs were significant for all three lower exposure groups and for permanent DMFS were significant for the two lower exposure groups against the 100%LEFW group. Mean ratios for the 0%LEFW compared to the 100%LEFW group were 2.10 (1.83-2.40) for dmfs and 1.82 (1.57-2.10) for DMFS.
CONCLUSION: Analysis of contemporary data representative of the Australian child population found consistent associations between %LEFW and childhood caries, which persisted when socioeconomic differences were adjusted across exposure groups, supporting the continued effectiveness of water fluoridation.
Harriehausen CX, Dosani FZ, Chiquet BT, Barratt MS, Quock RL. Fluoride Intake of Infants from Formula. J Clin Pediatr Dent. 2018 Oct 5. doi: 10.17796/1053-4625-43.1.7.
OBJECTIVE: This study aimed to assess fluoride intake in infants from formula reconstituted with water, with fluorosis risk in mind.
STUDY DESIGN: Data on water source, formula brand/type, volume of formula consumption and infant weight were collected for infants at two-, four-, six-, nine- and twelve-month pediatrician well child visits. Identified formula brands and water types were reconstituted and analyzed for fluoride concentration. Patient body mass and volume consumed/day were used to estimate fluoride intake from reconstituted formula. Descriptive statistics, one-way analysis of variance and chi-square tests were utilized.
RESULTS: All infants consumed formula reconstituted with minimally fluoridated water (0.0- 0.3 ppm). 4.4% of infants exceeded the recommended upper limit (UL) of 0.1mg/kg/day. Although mean daily fluoride consumption significantly differed among all groups, the proportion of infants at each visit milestone that exceeded daily fluoride intake of 0.1mg/kg/day was not statistically significantly different (p>0.05) for any age group. Predicted values calculated with optimally fluoridated water (0.7ppm) resulted in 36.8% of infants exceeding the UL.
CONCLUSIONS: Optimally fluoridated water may increase fluorosis risk for patients younger than six months. Future investigation should include multiple sites and multi-year follow-up to assess actual fluorosis incidence.