Plain language summary
Even though a small amount of exposure to fluoride can occur from accidental ingestion of topical dental products, fluoridated water and fluoride-rich and enriched foods and beverages represent the main sources of fluoride intake. The primary aim of this study was to evaluate the effects of fluoride exposure on thyroid function, specifically focusing on thyroid hormone levels and the prevalence of thyroid dysfunction. This research is a systematic review and dose-response meta-analysis, incorporating data from multiple observational studies and clinical trials. Results showed a clear pattern of association between fluoride content in drinking water consumed by the study participants and their circulating thyroid-stimulating hormones (TSH) concentrations. However, this occurred only above 2 mg/L of water fluoride. Authors concluded that at the highest levels of naturally occurring fluoride exposure there are detrimental effects on thyroid function and possibly thyroid disease risk, whose most evident and consistent finding is a dose-dependent increase in TSH concentrations associated with consumption of drinking water above 2.5 mg/L of fluoride.
Expert Review
Conflicts of interest:
None
Take Home Message:
- 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.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
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.
Clinical practice applications:
- 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.
Considerations for future research:
- 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.
Abstract
INTRODUCTION Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. METHODS We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. RESULTS Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 μIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. CONCLUSIONS Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.
Methodological quality
Jadad score
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Allocation concealment
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