Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis.

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• Fluoride is a naturally occurring mineral and is ingested via food, plants and water and primarily important for dental health.
• Excess intake might be due to dental products, fluoridated water, and enriched food and beverages.
• Suspected growth and/or neurodevelopment concerns in children necessitate assessment of fluoride concentrations in urine and/or serum.
• Adult hypothyroidism and goiter symptomatology may be associated with excess fluoride concentrations and similarly require investigation and careful elimination of exogenous sources.

Introduction

Excess fluoride intake is believed to be associated with thyroid disease risk by various biochemical means. A meta-analysis of relevant articles aimed to explore the association between fluoride concentrations in water, serum and urine with thyroid disorders in both children and adults. The Population, Exposure, Comparator, Outcomes, and Study design (PECOS) was based on the statement, “What is the effect of fluoride exposure on thyroid, according to a dose-response relation in humans?”

Methods

This systematic review was based on PubMed/MEDLINE, Web of Science, and Embase databases searches with 33 Articles meeting the inclusion criteria. This one-stage dose-response meta-analysis of original data included 45,000 participants from a predominantly Asian population (age range 6-76 years). Long-term fluoride exposure in both water and diet, and urinary or serum fluoride bio-markers, were assessed and compared to thyroid function and disease risk.

Results

• Drinking water, urinary serum concentration or daily fluoride intake were assessed for fluoride exposure.
• The average range of concentrations of fluoride in drinking water was measured at 0.08 to 25.10 mg/L (median: 0.80 and interquartile range (IQR): 2.04; n=25). Urinary fluoride concentrations ranged from 0.06 to 4.57 mg/L (median: 0.82 and IQR: 1.51; n=19). Serum fluoride concentration was 0.065 ± 0.17 mg/L (range: 0.03–0.395; n=11).
• Comparing highest and lowest drinking water fluoride content, the relative risk (RR) for goiter in children was stated as 1.79 (95% CI: 1.18; 2.73) and 7.93 (95% CI: 1.93; 32.59) for urinary fluoride content.
• Goiter risk in adults for water fluoride content was 7.38 (95% CI: 1.17; 46.53) with hypothyroidism risk at 1.62 (95% CI: 1.36; 1.93).
• A Canadian study showed positive association with hypothyroidism and fluoride intake via beverages (OR: 1.25; 95% CI: 0.99–1.57), and drinking water fluoride content (OR: 1.65; 95% CI: 1.04–2.60), but no such association with urinary fluoride concentration.

Conclusion

The data indicates an association between fluoride exposure and thyroid disease risk. However, the authors conclude that an increase in thyroid stimulating hormone is associated only in drinking water fluoride concentrations above 2.5 mg/L.

• Patients, both children and adults, with thyroid function symptomatology may benefit from fluoride urinary concentration assessment in conjunction with iodine status.
• Dietary and environmental sources of fluoride overexposure need to be carefully augmented given the role of fluoride in dental health.

• Larger homogenous studies are needed to establish the role of fluoride overexposure in thyroid health outcome.
• Data assessing the dose-response relationship between fluoride exposure and thyroid disease outcome is much needed.
• The effect of fluoride on iodine concentrations needs to be investigated given the important role of the latter on thyroid function.
• Genetic factors regarding the effect of fluoride overexposure furthermore warrant assessment.