2024: Effect of zinc intake on association between fluoride exposure and abnormal sex steroid hormones - NHANES, 2013-16

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Niu Z, Duan L, Du Y, Yu F, Chen R, Li Z, Ba Y, Zhou G - "Effect of zinc intake on association between fluoride exposure and abnormal sex steroid hormones among US pubertal males: NHANES, 2013-2016" Environ Sci Pollut Res Int 31(2):2759-2772 (2024). doi: 10.1007/s11356-023-31135-x.
https://link.springer.com/article/10.10 ... 23-31135-x

Abstract

Excessive fluoride exposure can disturb the balance of sex hormones. Zinc is essential for sex hormone synthesis and spermatogenesis. But it is not clear how zinc affects the relationship of fluoride exposure with abnormal sex steroid hormones. Here, a total of 1008 pubertal males from the National Health and Nutrition Examination Survey (NHANES) in two cycles (2013-2014, 2015-2016) were enrolled. The concentrations of water fluoride and plasma fluoride and the levels of serum testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured. Two 24-h dietary recall interviews were conducted to assess the dietary zinc intake. The relationships of fluoride exposure and zinc intake with sex hormones were examined using linear regression and logistic regression models, while the generalized additive model was used to evaluate their non-linear relationship. Our findings revealed that for every two-fold increase in plasma fluoride concentration, testosterone levels decreased by 7.27% (95% CI - 11.49%, - 2.86%) and estradiol levels decreased by 8.73% (95% CI - 13.61%, - 3.57%). There was also significant non-linear association observed between zinc intake and SHBG levels. Being in the first tertile of plasma fluoride had a 60% lower risk of high SHBG (OR = 0.40, 95% CI 0.18, 0.89) compared with being in the second tertile. When compared to the first tertile, being in the second tertile of zinc intake was associated with a 63% (OR = 0.37, 95% CI 0.14, 0.98) lower risk of high SHBG. Furthermore, we observed an interactive effect between the plasma fluoride and zinc intake on estradiol and SHBG, as well as the risk of high SHBG (P-interaction < 0.10). These findings suggest that fluoride exposure and zinc intake can affect sex steroid hormone levels and the risk of high SHBG. Notably, zinc intake may alleviate the increased risk of high SHBG and the abnormal changes of estradiol and SHBG caused by higher fluoride exposure.

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Licastro F, Mocchegiani E, Zannotti M, Arena G, Masi M, Fabris N - "Zinc affects the metabolism of thyroid hormones in children with Down's syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation" Int J Neurosci 65(1-4):259-68 (1992)
https://www.tandfonline.com/doi/abs/10. ... 9209003299
"Thus, the increased efficiency of the immune system and the normalization of some endocrine parameters by zinc supplementation suggests that zinc deficiency may play a crucial role in some of the pathological manifestations associated with the syndrome, such as infections and malfunctioning of the thyroid gland."

Bellisola G, Bratter P, Cinque G, Francia G, Galassini S, Gawlik D, Negretti de Bratter VE, Azzolina L - "The TSH-dependent variation of the essential elements iodine, selenium and zinc within human thyroid tissues" J Trace Elem Med Biol 12(3):177-82 (1998)

Li Y, Li X, Wei S - Effect of excessive fluoride intake on mental work capacity of children and a preliminary study of its mechanism" Hua Hsi I Ko Ta Hsueh Hsueh Pao 25(2):188-91 (1994)
"We made an investigation in 157 children, aged 12-13, born and grew up in a coal burning pattern endemic fluorosis area and an experiment on excessive fluoride intake in rat. The results showed: (1) Excessive fluoride intake since early childhood would reduce mental work capacity (MWC) and hair zinc content: (2) The effect on zinc metabolism was a mechanism of influence on MWC by excessive fluoride intake; (3) Excessive fluoride intake decreased 5-hydroxy indole acetic acid and increased norepinephrine in rat brain; whether this is also a mechanism of the influence on MWC awaits confirmation."

From our 2003 Newsletter on fluoride and zinc:

Fluorides cause "zinc deficiency". Both organic and inorganic fluoride compounds have shown to inhibit zinc containing enzymes, such as carbonic anhydrase (Dugad et al 1988,1989; Gelb et al, 1985) which is also now used as a marker for thyroid dysfunction (Hori et al, 1998).

Zinc depletion follows experimental fluorosis in mice (Kanwar and Singh,1981). In the liver a significant fall in the levels of zinc was registered. Effects were directly dose-dependent, just as is the case with fluoride-induced iodine deficiency. The liver is the major organ for thyroid hormone synthesis. Only 20% of T3, the biologically active thyroid hormone is manufactured in the thyroid itself. The rest occurs in peripheral tissue, mainly the liver.

In rats fed pure spring water (natural F concentration = 0.2 ppm) or spring water enriched with NaF to result in 0.8, 1.1 or 2.2 ppm F during 180 days, zinc ions were depleted in most tissues (Boeckhhaebisch & Oliveira, 1997).

Other work has also shown that a fluoride intake in rodents comparable to the total intake by man in fluoridated areas, leads to zinc deficiency in the testis, liver and kidneys (Krasowska, 1992, 1996).

Li et al (1994) showed that excessive fluoride intake since early childhood reduced mental work capacity and that the effect on zinc metabolism was a mechanism of influence by excessive fluoride intake, echoing earlier reports by Shen et al (1992).

Hlynczak et al (1980) also found significant alterations in workers exposed to fluorine compounds.