Benoit Follin-Arbelet, Bjørn Moum. Fluoride: A Risk Factor for Inflammatory Bowel Disease? Scand J Gastroenterol, 51 (9), 1019-24, Sep 2016
Although the association between inflammatory bowel disease (IBD) and oral hygiene has been noticed before, there has been little research on prolonged fluoride exposure as a possible risk factor. In the presented cases, exposure to fluoride seems indirectly associated with higher incidence of IBD. Fluoride toxicology and epidemiology documents frequent unspecific chronic gastrointestinal symptoms and intestinal inflammation. Efflux genes that confer resistance to environmental fluoride may select for IBD associated gut microbiota and therefore be involved in the pathogenesis. Together these multidisciplinary results argue for further investigation on the hypothesis of fluoride as a risk factor for IBD.
Tetsuo Nakamoto, H Ralph Rawls. Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life, The Journal of clinical pediatric dentistry. 42 (5), 325-330, 2018 doi: 10.17796/1053-4625-42.5.1
Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.
Stephen Peckham, Niyi Awofeso. Water Fluoridation: A Critical Review of the Physiological Effects of Ingested Fluoride as a Public Health Intervention, ScientificWorldJournal, 2014, 293019.
Fluorine is the world’s 13th most abundant element and constitutes 0.08% of the Earth crust. It has the highest electronegativity of all elements. Fluoride is widely distributed in the environment, occurring in the air, soils, rocks, and water. Although fluoride is used industrially in a fluorine compound, the manufacture of ceramics, pesticides, aerosol propellants, refrigerants, glassware, and Teflon cookware, it is a generally unwanted byproduct of aluminium, fertilizer, and iron ore manufacture. The medicinal use of fluorides for the prevention of dental caries began in January 1945 when community water supplies in Grand Rapids, United States, were fluoridated to a level of 1 ppm as a dental caries prevention measure. However, water fluoridation remains a controversial public health measure. This paper reviews the human health effects of fluoride. The authors conclude that available evidence suggests that fluoride has a potential to cause major adverse human health problems, while having only a modest dental caries prevention effect. As part of efforts to reduce hazardous fluoride ingestion, the practice of artificial water fluoridation should be reconsidered globally, while industrial safety measures need to be tightened in order to reduce unethical discharge of fluoride compounds into the environment. Public health approaches for global dental caries reduction that do not involve systemic ingestion of fluoride are urgently needed.
Goschorska M, Baranowska-Bosiacka I, Gutowska I, Metryka E, Skórka-Majewicz M, Chlubek D. Potential Role of Fluoride in the Etiopathogenesis of Alzheimer’s Disease. Int J Mol Sci. 2018 Dec 9;19(12). pii: E3965. doi: 10.3390/ijms19123965.
The etiopathogenesis of Alzheimer’s disease has not been fully explained. Now, the disease is widely attributed both to genetic and environmental factors. It is believed that only a small percentage of new AD cases result solely from genetic mutations, with most cases attributed to environmental factors or to the interaction of environmental factors with preexistent genetic determinants. Fluoride is widespread in the environment and it easily crosses the blood⁻brain barrier. In the brain fluoride affects cellular energy metabolism, synthesis of inflammatory factors, neurotransmitter metabolism, microglial activation, and the expression of proteins involved in neuronal maturation. Finally, and of specific importance to its role in Alzheimer’s disease, studies report fluoride-induced apoptosis and inflammation within the central nervous system. This review attempts to elucidate the potential relationship between the effects of fluoride exposure and the pathogenesis of Alzheimer’s disease. We describe the impact of fluoride-induced oxidative stress and inflammation in the pathogenesis of AD and demonstrate a role for apoptosis in disease progression, as well as a mechanism for its initiation by fluoride. The influence of fluoride on processes of AD initiation and progression is complex and warrants further investigation, especially considering growing environmental fluoride pollution.
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.
Duan Q, Jiao J, Chen X, Wang X. Association between water fluoride and the level of children’s intelligence: a dose-response meta-analysis. Public health. 2018 Jan;154:87-97. doi: 10.1016/j.puhe.2017.08.013.
OBJECTIVES: Higher fluoride concentrations in water have inconsistently been associated with the levels of intelligence in children. The following study summarizes the available evidence regarding the strength of association between fluoridated water and children’s intelligence.
STUDY DESIGN: Meta-analysis.
METHODS: PubMed, Embase, and Cochrane Library databases were systematically analyzed from November 2016. Observational studies that have reported on intelligence levels in relation to high and low water fluoride contents, with 95% confidence intervals (CIs) were included. Further, the results were pooled using inverse variance methods. The correlation between water fluoride concentration and intelligence level was assessed by a dose-response meta-analysis.
RESULTS: Twenty-six studies reporting data on 7258 children were included. The summary results indicated that high water fluoride exposure was associated with lower intelligence levels (standardized mean difference : -0.52; 95% CI: -0.62 to -0.42; P < 0.001). The findings from subgroup analyses were consistent with those from overall analysis. The dose-response meta-analysis suggested a significant association between water fluoride dosage and intelligence (P < 0.001), while increased water fluoride exposure was associated with reduced intelligence levels.
CONCLUSIONS: Greater exposure to high levels of fluoride in water was significantly associated with reduced levels of intelligence in children. Therefore, water quality and exposure to fluoride in water should be controlled in areas with high fluoride levels in water.