Public Health Impacts of Water Fluorides: Current Evidence from a Rapid Systematic Review.

Introduction

According to the 2022 WHO’s Global Oral Health Status Report [1], almost 2 billion people suffer from dental caries of permanent teeth, whereas 514 million children experience caries of primary teeth [1]. Globally, untreated dental caries (tooth decay) in permanent teeth is the most prevalent health condition, and its prevalence continues to rise globally [1]. Oral diseases disproportionately affect the poor, with a strong link between socioeconomic status and the prevalence and severity of these conditions across all age groups and countries. Furthermore, treatments are expensive and often excluded from health coverage [1].

Oral health is essential to overall health and quality of life. Dental caries, pain, and treatment can have a profound negative impact on general health and well-being, leading to pain, infection, and difficulties with eating and sleeping, as well as affecting self-esteem and psychological health [2]. Furthermore, poor oral health has been associated with increased risk of various conditions, including pneumonia, cardiovascular disease, stroke, low birth weight, and endocarditis [2].

Oral diseases impose a substantial global economic burden, with estimated annual costs of US$387 billion in direct expenditures and US$323 billion in productivity losses. Direct costs primarily arise from public and private spending on dental care, whereas indirect costs reflect reduced productivity. Among indirect costs, edentulism accounts for the largest share (US$167 billion). Dental caries contributes additional indirect costs of ~US$22 billion for permanent teeth and US$ 1.55 billion for deciduous teeth [3].

Apart from good oral hygiene and a balanced diet low in sugar consumption, fluoride has been widely recognized for its ability to reduce the prevalence and severity of dental caries [4]. Fluoride is a naturally occurring mineral found in soil, food, and water supplies, with concentrations varying by region. Due to its role in the mineralization of hard tissues, including bones and teeth, fluoride can have a significant public health impact in reducing the burden of dental caries [5]. This protective effect is primarily topical, as fluoride enhances remineralization, inhibits demineralization of tooth enamel, and disrupts bacterial metabolism, reducing acid production [5].

Although fluoride at low concentrations is well documented for preventing dental caries, higher concentrations of systemic fluoride exposure may result in the development of dental fluorosis. To optimize oral health outcomes while mitigating risks of dental fluorosis (the most sensitive effect), the WHO recommends a maximum fluoride concentration of 1.5 mg/L in drinking water [6].

To lower the prevalence of dental caries, fluoride has been incorporated into various public health initiatives, such as water, salt, and milk fluoridation programs, alongside its addition to dental products like fluoridated toothpaste, mouthrinses, and professionally applied varnishes and gels. Among public health fluoridation programs, water fluoridation remains the most widely practiced intervention to reduce the prevalence and severity of dental caries and address dental health inequalities. Water fluoridation programs serve ?400 million people across 25 countries [7], including the United States, Australia, New Zealand, Brazil, the United Kingdom, and Ireland.

A substantial body of evidence supports the benefits of water fluoridation for both children and adults, including the prevention of dental caries and reduction of oral health inequalities. Systematic reviews [[8], [9], [10]] have demonstrated that community water fluoridation reduces the incidence of dental caries by 26 to 44% in both children and adults, providing benefits across all age groups and socioeconomic strata, regardless of access to dental care. Despite the widespread use of fluoride toothpaste, water fluoridation offers a complementary and additive effect: whereas fluoride toothpaste delivers topical protection during brushing, fluoridated water ensures consistent low-concentration fluoride exposure throughout the day, supporting continuous remineralization of early carious lesions [11,12].

Despite its proven benefits, there is ongoing debate about the potential harmful effects of systemic fluoride exposure on human health. Although extensive research highlights both the dental benefits of fluoride and risks associated with high concentrations of fluoride intake, the broader nondental health implications of water fluoridation remain poorly understood. In some parts of the world, drinking water naturally contains fluoride concentrations greatly in excess of WHO recommendations, and this may increase risk of skeletal fluorosis [6]. Despite continued support from the United States Centers for Disease Control and Prevention [13] 2 states in the United States have recently passed legislation to ban water fluoridation, citing health concerns [14].

To address this gap, our rapid review aimed to systematically explore the existing literature on the nondental human health impacts of water fluoridation. Unlike previous studies, which predominantly rely on narrative literature review methods, this review adopts a systematic review methodology to synthesize evidence on the effects of water fluoridation on human health. In response to recent global debates on fluoride safety and use, a rapid systematic review was necessary to provide timely, robust, reliable, and valid evidence. Rapid reviews adhere to the core principles of systematic review, such as having clearly defined research questions and a transparent and replicable methodology, while streamlining certain steps, including limiting the publication date of eligible studies and reducing the number of reviewers involved at each stage of the review process, to deliver results more quickly. This approach balances methodological rigor with practical feasibility, making it particularly suitable for fast-moving policy environments where timely guidance is essential [15].

Research Question

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist [16] was used to guide the conduct and reporting of this systematic review. A protocol was developed a priori and registered on the Open Science Framework (Registration DOI: https://doi.org/10.17605/OSF.IO/JH245).

Results

Search results

The study selection process is illustrated in Figure 1. The database and search engine searches yielded a total of 1280 records, with an additional 50 records identified through gray literature and citation searching. After the removal of duplicates, 1143 unique records remained. A total of 1013 records were excluded during title and abstract screening, leaving 130 articles for full-text review. Of these, 72 were excluded for various reasons (including wrong setting, outcomes, interventions, study design, and/or study population), resulting in 58 studies being included in the final systematic review (Figure 1).

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FIGURE 1. PRISMA flow diagram; n = number.

Study characteristics

A summary of the study characteristics is presented in Table 2 and Figure 2, with detailed information provided in Supplementary File B.

TABLE 2. Summary of characteristics of included studies.

Classification	Frequency Number (%)
Study design
Cross-sectional	37 (63.8)
Cohort study	15 (25.9)
Case-control study	4 (6.9)
Ecological study	2 (3.4)
Year of publication
2010–2013	8 (13.6)
From 2014	50 (86.4)
Water fluoride concentration1
Low (? 0.7 mg F/L)	35 (60.3)
Optimal (< 1.5 mg F/L)	25 (43.1)
High (? 1.5 mg F/L)	18 (31.0)
Types of participants
Children (aged 0–12)	15 (22.5)
Adolescents (aged 13–17)	1 (1.7)
Adults (aged ? 18)	14 (24.1)
Children and adolescents	8 (13.8)
Children, adolescents, and adults	20 (37.8)

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Some studies involved participants exposed to varied concentrations of water fluoride concentration and were therefore counted in multiple categories, as classified by the original study authors.

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FIGURE 2. Comparative overview of fluoride exposure assessment methods, exposure grouping, concentration ranges, and analytical approaches across studies. Fluoride range: Green, amber, and red bars represent the fluoride concentration ranges for authors’ definitions of low-, medium-, and high-exposure groups, respectively. Blue bars indicate the overall fluoride range in studies where group classifications were not reported or not applicable. Stars mark the central value (mean or median) of the reported fluoride concentration, where available.

Findings from this systematic review indicate that most studies assessing the impact of water fluoride concentration on human health were conducted in the United States (n = 17), followed by Canada (n = 11), India (n = 10), China (n = 6), Iran (n = 4), and the United Kingdom (n = 3). Two studies each were conducted in Australia, South Korea, and Sweden, whereas 1 study originated from New Zealand. In terms of study design, most studies employed a cross-sectional approach (n = 37), followed by cohort studies (n = 15), case-control studies (n = 4), and ecological studies (n = 2). The included studies were published between 2010 and 2024, with the majority (n = 50) published from 2014 onward. Regarding the study populations, 14 studies focused exclusively on adults aged ?18 y. Three studies involved children aged 0 to 5 y, and 7 involved children aged 6 to 12 y. One study focused solely on adolescents aged 13 to 17 y. A total of 33 studies included participants of varied ages, with populations comprising children (0–12 y), adolescents, and adults in different combinations. Participants were exposed to a range of water fluoride concentrations, from 0.01 mg F/L to 10.30 mg F/L (Table 2).

Figure 2 presents a comparative overview of studies investigating fluoride exposure, highlighting key differences in measurement methods, exposure classification, concentration ranges, and statistical analyses. Fluoride exposure was assessed using diverse methodologies, including direct measurement from water sources, biomonitoring, and modeled estimates. Several studies categorized fluoride exposure into discrete groups (e.g., low, medium, high), whereas others treated it as a continuous variable. Reported exposure ranges varied considerably, from 0.01 mg F/L to 10.30 mg F/L, with some studies examining narrow exposure bands and others capturing a broader distribution. Measures of central tendency, such as the mean or median, were reported inconsistently across studies. Statistical approaches ranged from basic bivariate analyses to more complex multivariable models, reflecting heterogeneity in methodological rigor and analytical depth across the literature.

Assessment of methodological quality

To assess the methodological quality of the included studies, criteria from the MMAT were applied, specifically those relevant to nonrandomized controlled studies (including cross-sectional, cohort, and case-control designs) and quantitative descriptive studies (including ecological studies). Fifty-seven studies were appraised using the 5 criteria items under the nonrandomized controlled studies domain, whereas 1 ecological study was assessed using the 5 criteria under the quantitative descriptive domain.

Prior to the full quality assessment, the 2 MMAT prescreening questions were applied to each study to confirm eligibility for further appraisal. The detailed quality assessment outcomes, including the MMAT criteria applied and individual study scores, are presented in Figure 3. All included studies met ?1 of the prescreening criteria. Of the 58 studies assessed, 52 met all 5 MMAT quality criteria, and 4 met 4 out of 5. Overall, the majority of studies were assessed to be of “very good” methodological quality. Among the few studies that did not meet all criteria, the most common limitation was insufficient consideration or control of confounding variables in the study design and analysis.

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FIGURE 3. Methodological quality scores for included studies using the Mixed Methods Appraisal Tool. Color codes:

Green – Yes,

Red – No,

Yellow – Unclear,

Gray – Not applicable [[90], [91], [92], [93], [94], [95]].

Discussion

Recent global discussions on the use of fluoride for preventing dental caries have emphasized the need for timely, evidence-informed public health guidance. Using a rapid review approach, this study generated a structured overview of current evidence on the nondental health impacts of water fluoridation, balancing comprehensiveness with practical feasibility. This review systematically assessed multiple health domains to clarify potential risks and knowledge gaps. The findings indicate that community water fluoridation at concentrations ? 1.0 mg/L is not associated with adverse nondental health outcomes, whereas the evidence for concentrations between 1.0 and 1.5 mg/L is limited and less conclusive.

Despite 8 decades of public health implementation of water fluoridation, particularly at concentrations between 0.7 and 1.0 mg/L, the literature on its broader human health impacts remains fragmented and heterogeneous. The studies reviewed in this article investigated populations exposed to fluoride concentrations in drinking water ranging from 0.01 mg/L to 10.30 mg/L. This review focused on 8 key nondental health domains: cardiovascular outcomes, obesity, neurological development, cancer, thyroid function, skeletal health, birth outcomes, and metabolism. However, drawing robust conclusions within each of these domains is challenging, given the variability in study populations and settings. Studies were conducted across diverse countries, including the United States, Canada, China, India, Australia, South Korea, Sweden, and New Zealand, and in a variety of contexts such as homes, schools, communities, clinics, hospitals, and population databases. Additionally, there was significant variation in study designs (cross-sectional, case-control, cohort, interventional, and ecological) and methods for measuring fluoride exposure (public water records, groundwater samples, etc.). Moreover, inconsistencies in age groups and outcome measurement methods further complicate comparisons, making it difficult to establish definitive conclusions.

Across the 58 studies included in this rapid systematic review, the evidence largely supports the safety of current fluoridation concentrations (0.7–1.0 mg/L) commonly used in public health programs. However, evidence of potential adverse health effects becomes more pronounced at fluoride concentrations above those typically used in community water fluoridation (i.e., >1.0 mg/L). To facilitate dose–response interpretation, studies were stratified based on fluoride concentrations in drinking water: low/acceptable exposure (<1.5 mg/L), in line with the WHO guideline, and high exposure (>1.5 mg/L).

Thyroid-related outcomes were among the most frequently examined. Several studies reported statistically significant associations between high fluoride exposure and alterations in thyroid hormone regulation [28,39,[47], [48], [49], [50], [51], [52]]. Elevated TSH concentrations and altered T3 and T4 concentrations were observed in both children and adults [47,49,51,52]. However, other studies [49,55,69] found no associations, particularly in populations with adequate iodine intake. In general, none of these studies accounted for factors that influence thyroid function, which is strongly affected by nutrition and the gut–thyroid axis. Micronutrients such as iodine, selenium, iron, zinc, copper, magnesium, vitamin A, and vitamin B12 play key roles in hormone synthesis and regulation, and dietary imbalances can alter gut microbiota, impair nutrient absorption and immune regulation, and contribute to thyroid dysfunction [70].

Findings related to blood pressure and cardiovascular health were mixed. Although some studies observed possible links between higher fluoride exposure and increased hypertension prevalence [21, 22], others found no clear effects [18,20], or even inverse associations in younger populations [19]. However, none of these studies accounted for key confounding factors such as obesity, diabetes, smoking, and dietary habits, which are well-established risk factors for cardiovascular disease and hypertension [71].

Overall, evidence indicates that fluoride concentrations typical of community water fluoridation do not significantly harm bone health in the general adult population. However, in postmenopausal women, fluoride exposure at concentrations >1 mg/L has been associated with increased bone mineral density as well as a higher risk of fractures [59,60]. In children, fluoridated water at ?0.8 mg/L appears protective, correlating with a reduced risk of bone fracture [44].

Evidence concerning fluoride’s carcinogenic potential, particularly in relation to osteosarcoma, predominantly indicates no significant association between fluoride exposure and cancer incidence even at elevated concentrations [[41], [42], [43], [44], [45], [46]]. This finding is consistent with a recent systematic review [72] on fluoride exposure and risk of primary bone cancer, which reported no clear association in 12 out of 14 included studies. The 2 studies that did report a positive association between fluoride exposure and bone cancer in young males were published in 1992 [73] and 2001 [74], dates that fall outside the inclusion period for this rapid review.

Evidence for fluoride’s impact on birth outcomes was limited and inconsistent. Some studies reported associations between higher fluoride exposure and increased risk of low birth weight or preterm birth [64], whereas others found no significant relationships [62,63].

Findings related to metabolic health were sparse and heterogeneous. Conditions such as vitamin D deficiency, elevated blood glucose concentrations, and diabetes have been observed in some studies conducted in fluoride-endemic areas (fluoride concentration >1.5 mg/L) [65,66]. However, these conditions are also common in the general population and are influenced by many factors (such as inadequate sun exposure, poor diet, limited physical activity, socioeconomic disadvantage, genetics, and obesity [75]) that are unrelated to fluoride exposure. Other investigations have not found consistent associations between fluoride exposure and outcomes such as BMI or general metabolic dysfunction [23,24].

Findings in the neurodevelopmental domain included reports that prenatal maternal and early childhood fluoride exposure may be associated with cognitive development in young children [29, 31,37,39,40]. However, these findings have faced methodological criticism [76,77], and other studies have not replicated this association, particularly in settings with lower exposure concentrations and more robust adjustment for confounding factors [25,27]. A meta-analysis of 8 observational studies from nonendemic fluorosis areas found no statistically significant association between fluoride concentrations typical of community water fluoridation and children’s IQ scores. [78]. Similarly, recent reviews [[79], [80], [81]] on the effects of fluoride on cognitive neurodevelopment have reported possible IQ impairment only at exposures exceeding WHO guidelines, with no evidence of effects at lower concentrations (<1.5 mg/L). However, high heterogeneity across studies limits the validity of these findings. However, a recent systematic review and meta-analysis of 74 studies [82] reported that when fluoride was measured in water, the negative association with children’s IQ scores was significant only at higher concentrations (>2 mg/L) and not <1.5 mg/L. In contrast, when fluoride was measured in urine, the inverse association remained significant even at concentrations < 1.5 mg/L. Notably, nearly all studies included in this meta-analysis that used urinary fluoride as an exposure indicator relied on spot urine samples. Twenty-four-hour urinary fluoride excretion has been suggested as a valid and reliable indicator of short-term fluoride exposure. Since the concentration of analytes, such as fluoride, can fluctuate throughout the day, spot urine samples may not accurately represent total 24-h urinary excretion and, therefore, may not provide a true estimate of fluoride exposure. Furthermore, a recent study [83] reported significant differences in estimated fluoride intake and in the classification of children into intake categories (such as low, intermediate, and high exposure) when comparing urine-based estimates with those obtained from dietary and oral hygiene questionnaires. These findings underscore the limitations of relying solely on spot urine samples for assessing fluoride exposure.

Overall, this rapid review suggests that age, fluoride dose, and exposure context may influence potential health outcomes, though the evidence is mixed and methodologically heterogeneous. Some studies point to greater susceptibility in children, particularly regarding neurological and skeletal effects, whereas in adults, associations are more often reported in thyroid and skeletal domains. However, inconsistent findings, reliance on cross-sectional designs, variable exposure assessment methods, and potential risks of bias (such as confounding and selection bias) limit the validity of the evidence and the strength of the conclusions.

Although fluoride concentrations used in community water fluoridation (0.7–1.0 mg/L) are generally considered safe, some studies found statistically significant associations at concentrations above the WHO guideline (1.5 mg/L). The clinical significance of these findings remains uncertain, and potential risks may depend on total fluoride intake, pre-existing health conditions, and individual-level factors such as metabolic rate and nutritional status. Further high-quality longitudinal research is needed to clarify these relationships.

An understanding of fluoride’s pharmacokinetics and primary exposure pathways is essential for interpreting its health impact, given its biphasic nature—being beneficial at low concentrations but potentially causing adverse effects with excessive systemic exposure.

Fluoride is naturally present in trace amounts in the human body (?2.6 g) [12]. Although the dental health effects of fluoride are primarily topical, the nondental effects result from systemic ingestion. Systemic fluoride exposure mainly occurs through the consumption of fluoridated water, and in children, through unintentional ingestion of fluoride-containing dental products. Once ingested, fluoride is rapidly absorbed through the gastrointestinal tract, reaching peak plasma concentrations within 20 to 60 min [84]. Approximately 99% of the fluoride present in the body is found in calcified tissue like bones and teeth, with the kidneys responsible for most of its elimination [84]. Retention, however, varies by age, with about 35% retained in adults and ? 55% in children [85], reflecting differences in metabolism and skeletal growth. Several factors influence fluoride metabolism and modify the relationships among its intake, bodily retention, and associated health risks [84]. These factors include genetics, diet composition, nutritional status, physical activity, renal function, and acid-base balance [84].

Many studies estimate fluoride exposure based on community water concentrations; however, this does not fully capture individual intake from other sources. The primary contributors to systemic fluoride exposure are diet and inadvertent ingestion of fluoride-containing dental products. On average, toothpaste contributes ?6% of total fluoride intake in infants <12 mo of age and ?22% in children aged 1 to 4 y [86]. However, in children < 4 y, unintentional ingestion of toothpaste can account for ? 87% of total daily fluoride intake, depending on age, toothpaste quantity, and rinsing behavior [87]. In contrast, infants < 12 mo primarily receive fluoride through their diet, which includes fluoridated water, dietary fluoride supplements (such as fluoridated water, milk, and salt), and foods and beverages prepared with fluoridated water.

In some studies, urinary fluoride has been employed as a biomarker of fluoride exposure to evaluate its potential health effects. Although it is a reliable indicator of recent fluoride intake [85], urinary fluoride concentrations are influenced by various factors, including dietary patterns (e.g., vegetarian versus meat-based diets), altitude, hydration status, and renal function [84]. The predominance of cross-sectional study designs in the current literature constrains the ability to infer causality. Furthermore, methodological heterogeneity, along with variability in population demographics and regional risk profiles, contributes to inconsistent associations observed across health outcomes.

Across all nondental health impact domains examined in this rapid review, a key limitation of the included studies was the insufficient consideration of a comprehensive range of confounding factors. For instance, iodine deficiency, a leading cause of reduced IQ and impaired cognitive development, was rarely accounted for, despite its significant impact on neurological outcomes. Additionally, other environmental factors such as socioeconomic status, nutritional deficiencies, and coexposure to multiple pollutants (e.g., lead) were often overlooked. This lack of thorough confounder adjustment undermines the ability to isolate the possible effects of fluoride exposure on health outcomes and may contribute to the inconsistent findings observed in the literature.

Conclusion

This rapid systematic review indicates that community water fluoridation at concentrations between 0.7 and 1.0 mg/L is not associated with adverse nondental health effects in the general population. However, exposures exceeding the WHO guideline of 1.5 mg/L may increase risk of health effects, particularly among children and other susceptible groups. The review highlights the importance of considering total fluoride intake from multiple sources, age-related susceptibility, and individual factors such as metabolism and nutritional status. Given the heterogeneity of existing studies and inadequate adjustment for confounders, future research should comprehensively investigate potential health effects across all exposure concentrations, with particular focus on rigorous longitudinal studies with valid measurement of exposure that address these gaps.

The authors’ responsibilities were as follows – FVZ and EAK conceived and designed the study. FVZ and EAK conducted the screening of study titles, abstracts, and full texts, and assessed eligibility. JK and EAK performed data extraction and quality assessment. MD, FVZ, and EAK conducted the data synthesis. FVZ and EAK drafted the initial manuscript. AJM and MD critically reviewed the manuscript and provided intellectual feedback. FVZ had primary responsibility for the final content. All authors read and approved the final manuscript.

Data availability

All data underlying the results of this systematic review are available in the article and its supplementary materials. No new primary data were collected.

Funding

The authors reported no funding received for this study.