2026: Thyroid/parathyroid function and fluoride: role of mitochondrial DNA and SOD genetic variations

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Sun Q, Feng Z, Sun L, Li C, Wang G, Niu S, Wang Y, Wan H, Huang H, Zhu J, Yu F, Zhou G, Ba Y - "Thyroid/parathyroid function and fluoride: role of mitochondrial DNA and SOD genetic variations" J Endocrinol Invest (2026)
https://doi.org/10.1007/s40618-026-02823-5
https://link.springer.com/article/10.10 ... 26-02823-5

Abstract

Emerging evidence indicates excessive fluoride exposure damage thyroid/parathyroid, with oxidative stress and mitochondrial dysfunction as crucial mechanisms. However, epidemiological research on their involvement in fluoride-induced thyroid/parathyroid dysfunction and modification of oxidative stress-related SNPs are insufficient. Therefore, we conducted a cross-sectional study (n = 401) among children aged 7–13 in areas with drinking water fluoride exposure in Tongxu County, Henan Province, China. This study examined the associations between urinary fluoride (UF) levels and thyroid/parathyroid function in children, as well as mediation effect of DNA copy number (mtDNA-CN) and interactions between UF and superoxide dismutase (SOD) SNPs. The population was divided into two groups based on children safety guidance of UF (WS/T 256–2005), with respective UF levels of 0.73 mg/L and 2.21 mg/L. Results revealed that for each 1 mg/L increase in children UF, thyroid volume (Tvol) increased by 0.34 cm3 (95%CI: 0.21, 0.46), parathyroid hormone (PTH) levels decreased by 1.40 ng/L (95%CI: −0.21, 0.17), mtDNA-CN reduced by 0.13 unit (95%CI: −0.22, − 0.04). Notably, in girls, the UF-Tvol association was partially mediated by relative mtDNA-CN (mediation proportion = 33.08%). Additionally, the GG genotype carriers of SOD2 rs4880 exhibited a larger Tvol (P = 0.017). The TT carriers of SOD3 rs13306703 exhibited higher PTH levels (P < 0.001). GMDR analysis identified an interaction between SOD2 rs4880, SOD3 rs10370 polymorphisms, and UF on Tvol. These findings linked fluoride exposure to thyroid function change in children. mtDNA-CN partially mediating the UF-Tvol association in girls. Genetic variants in SOD2 and SOD3 may modify the effect of fluoride exposure on thyroid.

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PFPC Commentary:

This is the same Tongxu cohort explored in many previous studies, including the retracted 2020 Xu study on fluoride and IQ.

The children are consuming excessive amounts of iodine, as is clearly observable from Table 1:


A UIC above 300 μg/L is indicative of excessive iodine intake.

They previously stated that almost all children in this cohort had “sufficient” iodine intake, but their own urinary iodine data do not support that characterization. In school-age children, iodine adequacy ("sufficiency") is defined as a population median UIC of 100–199 μg/L (200–299 μg/L is above requirements -> "more-than-adequate"; ≥300 μg/L indicates excess). In this cohort, iodine intake levels are excessive.

Once again, the area with high fluoride is also the area with much higher iodine.

Here, “low UF” vs “high UF” does not isolate fluoride. The high-UF group also has much higher urinary iodine so the fluoride contrast is bundled with an iodine shift. Simply adjusting for iodine does not fix this unless the paper shows overlap and stratified or interaction analyses (UF within iodine strata, and UF × UI) for the main endpoints.

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Abuse of the scientific literature: citing irrelevant sources for deiodinase claims

Sun et al state:

"Studies have demonstrated that fluorine can readily displace iodine in the body, thereby disrupting the function of deiodinase enzymes [47, 48], which are the key enzymes mediating T4 activation to T3."

Here, reference #47 is the highly flawed review by D.T. Waugh on an alleged fluoride-induced inhibition of the sodium/iodide symporter - it never discusses deiodinase enzymes anywhere (!) - and #48 is a 2022 paper by Wu & Kluger. That study is a physical-organic kinetics study of a thiamin-derived Breslow intermediate where they measure (1) fluoride elimination from a CF3-substituted intermediate and (2) “iodination” as a chemical trapping reaction to probe rates. In that context, iodine is a reagent used to trap a carbanion form of the intermediate, not “iodine in the body,” not iodide, and not anything about thyroid deiodinases or T4 to T3 conversion.