Left ventricular mass and systolic function in children environmentally exposed to fluoride.

Abstract

Highlights

Urinary fluoride is associated with left ventricular mass increase in children.
Sex-specific associations were found for LVM increase associated with fluoride.
Urinary fluoride and dental fluorosis are associated with cardiac output.
Dental fluorosis is associated with an increase in systolic function parameters.
Early-life fluoride exposure is linked to anatomic and functional cardiac parameters.

Early life exposure to inorganic fluoride has been associated with adverse cognitive, renal and metabolic outcomes in children. However, scarce evidence exists linking fluoride exposure and echocardiographic parameters. A cross-sectional study, involving 374 children, was conducted in Chihuahua, Mexico. We assessed associations between urinary fluoride levels and dental fluorosis and echocardiographic parameters using multivariate linear regression models. The mean (total range) of fluoride concentrations in drinking water were 0.95 (0.01–5.84) mg/L, and urinary fluoride adjusted for specific gravity was 2.51 (0.67–6.75) ug/mL. Of the children, 38.0 % had dental fluorosis and 36.6 % were exposed to fluoride levels in drinking water above the WHO’s limit of 1.5 mg/L. The median (interquartile range) for left ventricular mass (LVM) was 73.58 (59.84–86.5) g. Fifty-nine percent of children had normal LV geometry pattern and 35.3 % had LV concentric remodeling. Urinary fluoride (third vs. first tertile) was associated with increased LVM (3.97 g; 95 % CI: 0.60–7.34 g; p = 0.021) and cardiac output (0.26 L/min; 95 % CI: 0.042–0.48 L/min; p = 0.019) in models adjusted for potential confounders. Cardiac output, ejection fraction (EF) and shortening fraction (SF) were positively and significantly associated with dental fluorosis (vs. no dental fluorosis) [(0.21 L/min; 95 % CI: 0.034–0.39 L/min; p = 0.020); (2.01 %; 95 %CI: 0.58–3.45 %; p = 0.006); (1.77 %; 95 % CI: 0.57–2.96 %; p = 0.004), respectively]. We found sex-specific associations for dental fluorosis and LVM increase with statistically significant associations in girls but not in boys (p-interaction = 0.018). Our findings showed that high fluoride exposure in early life is associated with structural and functional cardiac parameters in children environmentally exposed to this contaminant.

Graphical abstract

EXCERPTS (Tables not included)

1. Introduction

Fluoride exposure through drinking water is a cause of concern in many countries, including Canada, United States, Ghana, China, India, and Mexico (Archer et al., 2016; Barberio et al., 2017; Craig et al., 2015; Gonzalez-Horta et al., 2015; Huang et al., 2023; Maitra et al., 2021; Limon-Pacheco et al., 2018). Millions of children worldwide are exposed to fluoride concentrations in water that exceed the WHO’s limit recommendation of 1.5 mg/L (Saeed et al., 2020). Early life exposure to fluoride has been associated with adverse health effects such as low birth weight (Arun et al., 2022), neurotoxicity (Grandjean, 2019), dental fluorosis (DF) (Saldarriaga et al., 2021), alterations in thyroid and kidney functions (Saylor et al., 2022; Wang et al., 2020; Jimenez-Cordova et al., 2019), and higher cardiometabolic risk (India Aldana et al., 2024; Liu et al., 2020). Additionally, prenatal life might be a window of susceptibility to the toxic effects of fluoride (Krzeczkowski et al., 2024). However, there is a gap in the literature of studies linking early life fluoride exposure and anatomic and functional cardiac parameters (Karademir et al., 2011).

The human heart is one of the first organs to form and develop during embryogenesis and embryonic heart contractions can be detected between 21 and 24 days after conception. The normal development of the embryonic cardiovascular system and the placenta are needed for adequate blood flow, gas exchange, and nutrient delivery to the fetus (Tan et al., 2020). The heart continuously grows and develops from embryogenesis to childhood (Tan et al., 2020; Hietalampi et al., 2012). In parallel with heart growth, left ventricular mass (LVM) increases during childhood (Hietalampi et al., 2012).

Several factors influence LVM increase during childhood, including diet, sex, physical activity, renal function, and lipid levels (Hietalampi et al., 2012; Bjelakovic et al., 2020; Mencarelli et al., 2014). However, studies linking LVM and environmental exposure to contaminants during childhood are scarce (Karademir et al., 2011; Gump et al., 2023; Osorio-Yanez et al., 2015).

LVM increase in childhood might have long-term consequences on cardiovascular health later in life (Hietalampi et al., 2012). The left ventricle (LV) pumps oxygenated blood to the body and connects nearly all organs and systems. Thus, LV failure would likely impair other organ systems (Chengode, 2016). LVM increase and cardiac hypertrophy are well-recognized risk factors for myocardial infarction, stroke and adult mortality (Bang et al., 2017).

Echocardiography is a noninvasive method for measuring structural and functional parameters of the heart, including those used to calculate LVM, systolic and diastolic function, and heart valve performance, among others (Brady et al., 2016). One mechanism underlying early life exposure to fluoride and LVM increase is impaired fetal growth. Fluoride exposure increases the risk of low birth weight (LBW), and LBW, through increased risk of hypertension, might be related to LVM (Arun et al., 2022; Jiang et al., 2006; Lackland et al., 2003). The link between fluoride exposure and LVM increase might also be explained, considering fluoride’s endocrine-disrupting capacity. Fluoride alters lipid levels and thyroid hormones, which might lead to cardiac effects (Wang et al., 2020; India Aldana et al., 2024; Bjelakovic et al., 2020; Fazio et al., 2004). Finally, evidence from animal experiments has indicated that fluoride exposure produces oxidative stress, calcium metabolism imbalance and mitochondrial alterations, which are mechanistically related to cardiac hypertrophy (Quadri et al., 2018). In cardiac hypertrophy, cardiomyocytes exhibit a high rate of cell death, especially apoptosis, which might result in reduced contractility and decreased systolic function (Nadruz, 2015). LVM increase as a compensatory mechanism might result from increased cardiac output (CO) and blood pressure (BP) (Weaver et al., 2009; Daimee et al., 2017). The evidence linking fluoride exposure and BP increase in children and adolescents is inconclusive, with some studies finding positive and significant associations and others a decrease in BP related to fluoride (Liu et al., 2020; Ballantyne et al., 2022; Guo et al., 2023; Hung et al., 2023). To our knowledge, no previous study has evaluated associations between fluoride exposure and echocardiographic parameters of LV structure and function in children. Due to the scarcity of available literature linking fluoride exposure and cardiovascular outcomes at the epidemiologic level, this study aimed to assess associations between urinary fluoride levels, LVM, LV systolic function and CO in children environmentally exposed to fluoride through drinking water.

2. Methods

2.1. Child selection and recruitment

We conducted a cross-sectional study from October to November 2015 involving 417 schoolchildren residing in Hidalgo del Parral and Aldama, Chihuahua, Mexico. This study was approved by the Institutional Review Board of CINVESTAV-IPN (Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional) (COBISH-CINVESTAV-025/2015). We previously published the recruitment process and school selection from these two municipalities (Jimenez-Cordova et al., 2019). Briefly, we recruited children from two schools, one in Hidalgo del Parral and the second in Aldama based on the following criteria: 1) differential fluoride exposure in drinking water (0.18 mg/L in Hidalgo del Parral and 2 mg/L in Aldama); 2) similar levels of arsenic in the water (10 ug/L in Hidalgo del Parral and 9.7 ug/L in Aldama) (Gonzalez-Horta et al., 2015); and 3) at least 400 students per school. Children were invited to participate through school meetings conducted with parents and school authorities. Initially, of the total number of students enrolled in the schools, approximately 39 % (N = 179) from Hidalgo del Parral and 52 % (N = 238) from Aldama agreed to participate. Before enrollment, parents read and signed an informed consent form. Children signed a written informed assent document. We included children who had at least two years of residence in the locality and reported drinking tap water. We excluded children with diagnosed chronic diseases such as diabetes and cardiovascular disease. Of the 417 children who agreed to participate, 43 were excluded due to incomplete data or previously diagnosed chronic diseases. Thus, the analytical sample size was 374.

We interviewed parents or caregivers to collect information on general characteristics, drinking water sources, potential sources of fluoride exposure, socioeconomic status (SES), time of residence in Aldama or Hidalgo del Parral, medical history, physical activity, diet, secondhand smoke (SHS) exposure, and medication. We classified SES status according to the Mexican Association of Marketing and Public Opinion Agencies (AMAI) (López-Romo, 2011). We assessed physical activity and dietary information using the Physical Activity Questionnaire for Children (PAQC) and 24-h dietary recall, respectively (Kowalski et al., 2004; Pérez-Lizaur AB et al., 2014).

… 3. Results

3.1. Study population characteristics

Table 1 shows the sociodemographic, anthropometric, and biochemical characteristics for all the study participants and stratified by sex. For the whole population, the median age was 9.0 years, IQR 7 to 10. Of the participants, 53.2 % were girls and 46.8 % were boys. The distribution of children in the two localities was 41.4 % from Hidalgo del Parral and 58.6 % from Aldama. Most of the children (88.4 %) have resided in the study area for their entire lives, with a mean residence time (total range) of 8.2 (2–12) years; time of residence was not different according to locality or sex (data no shown). The median (IQR) of z-score for BMI was 0.29 (-0.39 to 1.02). Most children had normal weight (73.0 %), while 20.3 % were overweight and 5.1 % were obese. The body fat percentage was very high for 22.2 % of the participants (Table 1).

The mean value of fluoride levels in drinking water was 0.95 mg/L, with a minimum of 0.01 and a maximum of 5.84 mg/L (data not shown). The median (IQR) of fluoride in drinking water was 0.28 (0.13–2.0) mg/L (Table 1). Most of the children (62.2 %) were exposed to fluoride levels in drinking water below 1.5 mg/L; we did not have information of fluoride levels in drinking water for four children. The mean and median urinary fluoride concentrations adjusted for specific gravidity were 2.51 ug/mL and 2.3 ug/mL, respectively. The Dean index indicated that 33.2 % of the participants had no DF, while 2.7 % and 0.8 % had moderate and severe DF, respectively (Table 1).

On the other hand, arsenic levels in the 10 % of water samples had a mean value of 8.91 ug/L, with a minimum and maximum value of 6.4 ug/L and 10.0 ug/L, respectively (data not shown).

Regarding sex, we found differences between boys and girls for SBP, body fat, HDL cholesterol, triglycerides, urinary fluoride and fluoride levels in drinking water. For example, SBP and HDL cholesterol were higher in boys than girls. Similarly, urinary fluoride levels and fluoride concentrations in drinking water were higher in boys than girls. On the other hand, body fat percentage and triglycerides were higher in girls than boys (Table 1).

We previously published differences between children from Aldama and Hidalgo del Parral (Jimenez-Cordova et al., 2019). Overall, statistically significant differences between two localities were found for children’s age, socioeconomic status, SBP, physical activity and fluoride exposure levels (data not shown).

… 3.2. Echocardiographic parameters in children environmentally exposed to fluoride

Table 2 shows the echocardiographic parameters for all children, boys and girls. Considering all participants, the median LVM (IQR) was 73.58 (59.8–86.5) g. The median values for EF and SF were 70.7 % and 39.4 %, respectively. The median (IQR) for CO was 3.08 (2.48–3.72) L/min. For almost all the echocardiographic parameters, we found differences between boys and girls (Table 2). Fig. 1 shows cardiac geometry parameters for all participants, boys and girls. Considering all children, we found a prevalence of 59.0 % for normal LV geometry, 35.3 % for concentric remodeling, 3.0 % concentric hypertrophy, and 2.7 % for eccentric hypertrophy. Differences in LV geometry were found between boys and girls (P-Value<0.0001). For example, higher percentage of concentric remodeling was found in girls than boys (42.1 vs. 27.6 %)….

3.3. Associations between fluoride exposure and left ventricular mass

Urinary fluoride as a continuous variable was marginally associated with LVM increase (Table 3). In stratified analyses by sex, we found that the increase in LVM associated with fluoride as continuous variable was mainly driven by girls (p-interaction = 0.08; model 2). In girls, we found an increase of 2.27 g (IQR: 0.77–3.77 g; p = 0.003; Model 2) associated with urinary fluoride. Oppositely, urinary fluoride was not associated with LVM in boys (estimate: -0.30; 95 % CI: -2.17, 1.57; p = 0.75; Model 2).

… Regarding urinary fluoride in tertiles, we found an increase in LVM of 3.97 g (95 % CI: 0.60–7.34 g; p = 0.021) associated with the third tertile (vs. first tertile) for all participants (Model 2; Table 3). The p for interaction between urinary fluoride tertiles and sex was not statistically significant. However, we found that the increase in LVM associated with urinary fluoride tertiles was statistically significant only in girls.

Finally, we found no significant associations between DF categories and LVM for all participants. However, in stratified analyses by sex, we observed significant associations (p=0.003; Model 2) between mild to severe DF (vs. reference category) and LVM increase only in girls (P for interaction = 0.02; Model 2) (Table 3)…

3.4. Associations between fluoride exposure, cardiac output and systolic function parameters

Urinary fluoride, as a continuous variable, was not associated with CO (Fig. 2; Supplemental Table 2). However, we observed an increase in CO in the third tertile compared to the first tertile of urinary fluoride: 0.26 L/min [(95 % CI: 0.04, 0.48 L/min; p = 0.019); Model 2]. Similarly, an increase of CO was found in participants with mild to severe DF compared to normal or questionable DF [estimate: 0.21 L/min; (95 % CI: 0.034, 0.39 L/min); p = 0.020; Model 2).

… Urinary fluoride was not associated with EF or SF (Fig. 2; Supplemental Table 2). However, DF mild to severe was associated with an increase in EF [2.01 %; 95 % CI: 0.58, 3.45 %; p = 0.006; (Model 2)] and SF [1.77 %; 95 % CI: 0.57, 2.96 %; p = 0.004) (Model 2)] compared to normal or questionable DF category (Fig. 2; Supplemental Table 2). We found no differences between boys and girls for CO, EF and SF and all p for interaction were not statistically significant.

4. Discussion

We aimed to investigate the association between urinary fluoride and echocardiographic parameters of LV structure and function in children environmentally exposed to fluoride. The key findings of our study can be summarized as follows: (i) concentric remodeling was highly prevalent in children; (ii) urinary fluoride and DF were associated with LVM increase, and girls were more susceptible to LVM increase associated with fluoride exposure parameters; (ii) CO was associated with urinary fluoride and DF; (iii) children with DF had increased systolic function parameters (EF and SF) compared to children with no DF; (iv) no differences between boys and girls were found for CO and systolic function parameters.

4.1. Fluoride levels in our study setting

Compared to other epidemiologic studies in Mexico, concentrations of fluoride in drinking water in our study setting were lower than those reported in Guanajuato, Mexico (up to 7.0 mg/L) and higher than those reported in Mexico City (0.15–1.38 mg/L) (Morales-Arredondo et al., 2023; Bashash et al., 2017). To note, almost 40 % of our study participants were exposed to fluoride in drinking water above the WHO’s limit of 1.5 mg/L. Other sources of fluoride exposure in the population may include dietary sources, dental products, and salt consumption (Cantoral et al., 2019; Hernandez-Guerrero et al., 2008). Salt is fluorinated in Mexico as part of a national program to prevent dental caries (Secretaría, 1995).

The urinary fluoride levels in our study participants (2.3 ug/mL) were approximately two times higher than the biological equivalents (BEs) of urinary fluoride (1.2 ug/mL) (Aylward et al., 2015). Finally, urinary fluoride levels in our population were higher than those reported for children in the US (1.29 mg/g of creatinine), with fluoride intake for caries prevention from 0.05 to 0.07 mg/kg of body weight/day (Warren et al., 2009).

4.2. Left ventricular geometry in children exposed to fluoride

Although most of the children had normal LV geometry pattern (59.0 %), 35.3 % had LV concentric remodeling. LV concentric remodeling (normal mass and increased wall thickness) is a precursor to LV concentric hypertrophy (increased mass and wall thickness). While generally reversible, LV concentric remodeling tends to result in higher LVM compared to truly normal geometry (Gaasch et al., 2011).

No previous study has evaluated the prevalence of LV geometry patterns in children environmentally exposed to fluoride. However, LV geometry patterns have been characterized in pediatric obesity. In one study, 42 % of obese children with normal blood pressure had concentric remodeling and 23 % had concentric hypertrophy; authors did not find associations between concentric remodeling and SF, a systolic function parameter (Dhuper et al., 2011). In our study, 35 % of children had concentric remodeling, 3.0 % had concentric hypertrophy, and all children, regardless of LV geometry pattern had normal FE and SF values (>50 and > 25 %, respectively). Therefore, the prevalence of concentric remodeling in our participants is lower than in other populations with cardiovascular risk factors such as obesity. The concentric remodeling observed in our population might result from the interplay of various cardiovascular risk factors such as increased BMI, lipid levels and glucose levels. However, it is possible that fluoride exposure might contribute to concentric remodeling since fluoride is significantly associated with increased LVM. Further studies with larger sample sizes are needed to examine associations between fluoride exposure and LV patterns, particularly concentric remodeling, in childhood.

4.3. Fluoride exposure and left ventricular mass increase

We observed a significant association between urinary fluoride levels and an increase in LVM. To the best of our knowledge, very few studies have evaluated cardiac structure and function in relation to fluoride exposure at population level. For example, a cross-sectional study in Turkey reported no differences in echocardiographic parameters in exposed participants (35 children with DF and urinary fluoride >0.6 ug/mL) compared to the control group (26 children without DF). However, the authors found an increase in QT interval prolongation measured by electrocardiogram in the exposed group compared to the control group [390.6 (309.0–418.5) vs. 366.8 (318.2–468.5) msec, respectively] (Karademir et al., 2011). LVM increase is often associated with QTc prolongation since LVM worsens the transmural dispersion of myocardial repolarization and increases the risk of arrhythmias (Cava et al., 2023). Thus, the QTc interval prolongation associated with fluoride in Turkish children aligns, to some extent, with our findings.

Our results contrast with those from a previous study conducted by Varol et al. (2010) in adults from Turkey. They reported no statistically significant differences (p = 0.12) in LVM (g) in healthy adults (156.7 ± 26.5 g, mean age 32.7 ± 8.8 years) compared to the fluoride-exposed group (147.5 ± 32.0 g, mean age 33.9 ± 8.6 years) (Varol et al., 2010). Differences in findings might be related to sample size, fluoride exposure levels, and stage of life, among other factors.

On the other hand, analyses testing for interaction effects between fluoride exposure and sex indicated that girls drove the association between fluoride exposure and LVM increase. These results might be explained at least in part because of higher fat percentage and triglycerides levels found in girls compared to boys in our study setting.

Adiposity can induce structural and functional changes in the heart independently of blood pressure increase. Interstitial fat infiltration and accumulation of triglycerides contribute significantly to LVM increase and cardiac hypertrophy (Murdolo et al., 2015). According to our findings, two previous epidemiologic studies have suggested higher cardiometabolic risk in girls but not in boys (Liu et al., 2019, 2020). Further studies should be conducted regarding effect modification by sex in cardiometabolic outcomes associated with fluoride.

Experimental evidence suggests a potential relationship between fluoride and cardiac hypertrophy. For example, a study with male Wistar rats reported heart weight increase in rats exposed to 300 mg/L of sodium fluoride (NaF) in drinking water compared to the control group (0.49 ± 0.53 g vs. 0.41 ± 0.07 g, respectively). However, they did not find differences in heart weight per total body weight (g/g) in the control group compared to the exposed groups (150, 300 and 600 mg/L of NaF) (Oyagbemi et al., 2017). On the other hand, a study on females Xenopus laevis found that NaF administration (0, 100 and 200 mg/L) in drinking water for 90 days caused hypertrophy of myocardial cells and atrophy of myocardial fibers in the exposed groups compared to the control (Wang et al., 2023). Therefore, experimental evidence also suggested that fluoride might contribute to increased cardiac mass and hypertrophy.

The heart comprises multiple cell types, including cardiomyocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, and immune cells. Since most of the cardiomyocytes are not able to divide, cardiomyocyte enlargement is associated with hypertrophy. Several molecular events accompany cardiac hypertrophy, such as calcium imbalance, cell death (apoptosis and autophagy), fibrosis, and angiogenesis, among others (Bernardo et al., 2010; Tham et al., 2015). For example, Quadri and colleagues reported an increase in pro-inflammatory cytokine (IL-17), tissue calcium levels, oxidative stress biomarkers, lipid peroxidation, and apoptosis in cardiac tissue of rats exposed to fluoride (50 and 100 ppm, in drinking water ad libitum) for 75 days (Quadri et al., 2018). Additionally, an increase in LVM is linked to parathyroid hormone (PTH); in this sense, experimental evidence suggests that fluoride might affect PTH, which is related to bone, renal, and cardiovascular outcomes, including LVM increase (Wang et al., 2015; Goettsch et al., 2014). All these mechanisms might explain, at least in part, the increase in LVM related to fluoride exposure.

4.4. Fluoride exposure and cardiac output

The CO in the study participants was 3.08 (2.48–3.72) L/min, within normal values reported for children, 3.18 L/min (Crittendon et al., 2012). CO is the amount of blood the heart pumps in a minute and depends on heart rate, contractility, preload, and afterload (Vincent, 2008). An increase in CO may increase LVM, or vice versa, an increase in LVM can raise the CO (Carreno et al., 2006). Due to the cross-sectional nature of our study, we could not determine whether CO was the cause or the consequence of LVM increase.

We are aware of only one study with dogs that were intravenously administered with NaF. Compared to controls, they found no significant changes in systemic arterial pressure, heart rate, CO, and myocardial contractility (dP/dT) in the low and high fluoride exposed groups, 800 uM and 1300 uM of fluoride in plasma, respectively (Gaugl et al., 1983). Our findings do not align with this experimental study in dogs. Similar to what was found with urinary fluoride, we observed positive and significant associations between DF and CO. The critical period for the development of DF in the first teeth is between 6 and 9 months of age. Although there is still controversy, DF is more related to long-term fluoride accumulation during child growth and development rather than exposure limited to a specific critical period (Saldarriaga et al., 2021; Ballantyne et al., 2022; Levy et al., 2002). Thus, our findings suggested that recent (urinary) and long-term exposure (DF) are associated with CO. Further studies are needed to confirm our results and examine the mechanisms underlying the fluoride effect on CO increase.

4.5. Systolic function parameters and fluoride exposure

Urinary fluoride was not associated with systolic function parameters; however, we observed an increase in EF and SF in children with DF compared to those without DF, suggesting that the increase in these parameters is mainly associated with long-term rather than short-term fluoride exposure.

There are no previous epidemiologic studies linking fluoride exposure and systolic function parameters. We are aware of only one epidemiologic study in adults from Mongolia that found an increase in left ventricular myocardial performance index (MPI) in participants with fluorosis compared to controls (0.62 ± 0.15 ms vs. 0.49 ± 0.10 ms; p < 0.001, respectively). MPI combines both systolic and diastolic performances (Varol et al., 2010). Thus, our results are in some degree consistent with the results of Varol et al. (2010), which reported cardiac function alterations in people exposed to fluoride.

There are a couple of experimental studies linking fluoride exposure and contractility. For example, a study with dogs showed that fluoride exposure (800 uM and 1300 uM, 3h infusion) did not modify cardiac contractility (dp/dt) (Gaugl et al., 1983). Oppositely, a study with mice exposed to NaF (0, 30, 70, and 150 mg/L) for 4 weeks found that fluoride decreases cardiac contractility (Xie et al., 2020). Contractility is strongly related to EF, preload (the amount of ventricular stretch at the end of diastole) and afterload (systemic vascular resistance). Fluoride might modify cardiac contractility, either preload or afterload. Although there are no epidemiologic studies linking fluoride and EF, there is experimental evidence suggesting that fluoride affects actine-myosin interactions, which are closely related to variables needed to construct the EF parameter. For example, in Caco-2 cells, fluoride exposure increased myosin light chain II (MLC2) phosphorylation and produced remodeling of actin filaments (F-actin) (Li et al., 2023).

The results of our study should be interpreted considering its strengths and limitations. The strengths of our study include the echocardiographic measurements in children environmentally exposed to fluoride, short and long-term fluoride exposure variables, and the rich covariate data of our study participants.

We acknowledge certain limitations, such as the cross-sectional study design that did not allow us to establish causality and the temporality of the cardiovascular outcomes in relation to fluoride exposure. Selection bias might also impact our results because we selected participants from schools of two localities based on fluoride and arsenic concentrations in drinking water. Additionally, we were not able to consider the contribution of other sources of fluoride exposure to the total burden of fluoride in this population. We also lacked information on other environmental contaminants that might increase cardiovascular risk early in life, such as lead and ambient air pollution (Friedman et al., 2023; Liu et al., 2023). We did not have information on other contaminants in drinking water, foods, or even micronutrients that might modify the toxic effects of fluoride.

5. Conclusions

Our findings indicate that early-life exposure to high fluoride levels, twice the BEs, is associated with significant changes in structural and functional cardiac parameters in children. Specifically, urinary fluoride levels were associated with an increase in LVM and CO. Girls were more susceptible to LVM increase related to fluoride. Additionally, DF was associated with an increase in CO and systolic function parameters, such as EF and SF in all participants.

These results suggest that both recent (as indicated by urinary fluoride levels) and long-term fluoride exposure (as indicated by DF) might affect heart structure and function in children. Future longitudinal studies are necessary to confirm our findings and to elucidate the mechanisms underlying the relationship between fluoride exposure and cardiac outcomes.

The observed associations between fluoride exposure and cardiac parameters underscore the importance of monitoring and managing fluoride levels in drinking water to protect children’s cardiovascular health.

Appendix A. Supplementary data

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Data availability

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References

Archer et al., 2016
N.P. Archer, T.S. Napier, J.F. Villanacci
Fluoride exposure in public drinking water and childhood and adolescent osteosarcoma in Texas
Cancer Causes Control, 27 (7) (2016), pp. 863-868