Abstract
Context
While fluoride has been added to drinking water and dental products for decades in order to prevent tooth decay, there are growing concerns about its potential toxicity. Given that fluoride is primarily excreted in urine, an important question that has not been examined is whether among those whose drinking water is fluoridated, impaired renal function is associated with higher levels of circulating fluoride.
Objective
To examine the association between drinking water and plasma fluoride and its modification by renal function. Design, Setting, and Participants: Participants in the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 with measures of fluoride in plasma and drinking water and renal function. These measures were only available in adolescent age 12–19 years.
Outcomes
Plasma fluoride levels and their modification by strata of renal function, measured by the estimated glomerular filtration rate (eGFR).
Results
Among 1841 healthy adolescents, a 10 ml/min/1.73 m (Penman et al., 1997) lower eGFR and a 1 mg/L higher drinking water fluoride concentration were associated with a 0.02 (95%CI -0.02, 0.03) umol/L and 0.23 (95%CI 0.15,0.30) umol/L higher adjusted plasma fluoride level, respectively. The association of water and plasma fluoride levels was most robust among those with lower renal function (multiplicative interaction p value < 0.001). For adolescents in the lowest eGFR quartile, a 1 mg/L higher drinking water fluoride concentration was associated with a 0.35 (95%CI 0.21,0.48) umol/L higher plasma fluoride level, compared to 0.20 (95%CI 0.14,0.26) umol/L in the highest eGFR quartile. Restriction to those with measurable plasma fluoride levels yielded similar results.
Conclusions
Water fluoridation results in higher plasma fluoride levels in those with lower renal function. How routine water fluoridation may affect the many millions of Americans with Chronic Kidney Disease, who are particularly susceptible to heavy metal and mineral accumulation, needs to be further investigated.
*Original abstract online at https://www.sciencedirect.com/science/article/abs/pii/S0013935122009306
Excerpt:
Introduction
Fluoride enrichment of drinking water is one of the major public health advances of the 21st century. While fluoride toxicity has been reported with acute intoxication (Gessner et al., 1994; Penman et al., 1997), emerging data suggests that even low levels of exposure may be associated with adverse effects in vulnerable populations (Wei et al., 2021a; Yasmin and Ranjan, 2015; Riddell et al., 2019; Green et al., 2019). While there are known determinants of fluoride toxicity, including age, dose and chronology of exposure, and a range of socioeconomic and nutritional factors (Liu et al., 2021; Mascarenhas, 2000; Skotowski et al., 1995; Van Der Hoek et al., 2003), the role of renal function has received less attention. Like most heavy metals and minerals, fluoride excretion occurs primarily through the kidney, a combination of glomerular filtration and tubular secretion (Schiffl and Binswanger, 1980). While previous studies have examined for potential fluoride nephrotoxicity (Malin et al., 2019a; Xiong et al., 2007; LEONE et al., 1954; Singh et al., 2001; Wimalawansa, 2020a; Wimalawansa, 2020b; Lantz et al., 1987), whether decreasing renal function might lead to progressive fluoride accumulation has not been addressed.
Section snippets
Sample
A complex, multi-stage probability sample of the United States civilian, noninstitutionalized population designed to assess the health and nutritional status of adults and children, NHANES combines granular historical, physical, and laboratory examinations to provide nationally representative data at two-year cycles, with no repeat individual measurements. Of 20,146 individuals included in the 2013–14 and 2015–16 cycles, household drinking water was measured among 8087 children (> 19 years). We…
Results
Among 1841 healthy adolescents, the average (SD) eGFR was 132.2 (15.1) ml/min/1.73 m (Penman et al., 1997), and average (SD) plasma and water fluoride levels were 0.38 (0.22) umol/L and 0.56 (0.32) mg/L respectively. Across quartiles of eGFR, there was no meaningful difference in levels of drinking water fluoride (Table 1), but eGFR was indirectly associated with plasma fluoride levels (Fig. 1). Water fluoride concentrations were directly associated with plasma levels (supplemental figure 1),
Conclusion
The association between drinking water and plasma fluoride levels is significantly greater in adolescents with lower renal function. Whether patients with CKD have heightened susceptibility to fluoride toxicity from environmental levels of exposure will require further study.
Credit author statement
Conceptualization, data analysis, manuscript preparation – Danziger; Statistical analysis – Dodge; Manuscript review, supervision – Hu.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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