Background: Chronic exposure to fluoride in drinking water causes an increase in plasma fluoride levels that is related to a reduction in calcium transport across the renal tubule endoplasmic reticulum and plasma membrane. In the present study, it was hypothesised that varying levels of fluoride present in drinking water are associated with serum levels of calcium and the related hormones vitamin D and parathyroid hormone in pregnant women and newborn infants.
Methods: This cross-sectional study included two groups based on the fluoride concentration in drinking water. One group was considered low/optimum in which the fluoride concentration in drinking water was <1 ppm, and the other group was considered a high fluoride group with <1 ppm fluoride in drinking water. In each group, 90 pregnant women were recruited at the hospital during delivery. The participants were given a questionnaire regarding their medical history, sunshine exposure duration, and supplement use and a food frequency questionnaire (FFQ). Fluoride was measured in drinking water, urine, maternal serum and cord blood. Serum calcium, vitamin D, and parathyroid hormone were measured in a fully automated analyser.
Results: In pregnant women, drinking water that contained fluoride was significantly positively correlated with urine and blood serum. Low mean concentrations of vitamin D and deficient (<10 ng/ml) vitamin D were more prevalent among the high fluoride group irrespective of diet, sunshine exposure and supplementation. Serum calcium and parathyroid hormone (PTH) levels were significantly lower in the high fluoride group than in the low/optimum fluoride group in both pregnant mothers’ blood and cord blood.
Conclusions: Drinking water with high fluoride levels was significantly associated with calcium and the related hormones vitamin D and parathyroid hormone.
*Original abstract online at https://www.nature.com/articles/s41430-020-00707-2
1.Sananda D, Biplab G. Fluoride fact on human health and healthproblems: a review. Med Clin Rev. 2016;2:1–6. https://doi.org/10.21767/2471-299X.1000011.
2. Fluoride in drinking-water. Background document for development of WHO guidelines for drinking-water quality. WHO/SDE/WSH/03.04/96.
3. Chen S, Li B, Lin S, Huang Y, Zhao X, Zhang M, et al. Change of urinary fluoride and bone metabolism indicators in the endemic fluorosis areas of southern china after supplying low fluoride public water. BMC Public Health. 2013;13:156. https://doi.org/10.1186/1471-2458-13-156.
4. Thippeswamy HM, Kumar Nanditha, Anand SR, Prashant GM, Chandu GN. Fluoride content in bottled drinking waters, carbonated soft drinks and fruit juices in Davangere city, India. Indian J Dent Res. 2010;21:528–30.
5. Patsouri K. Re-examining the fluoride intake during pregnancy: a necessity or not for the incoming member. Int J Dent Med Res. 2015;1:150–6.
6. Kanduti D, Sterbenk P, Artnik B. Fluoride: a review of use and effects on health. Mater Sociomed. 2016;28:133–7.
7. Bashash M, Thomas D, Hu H, Martinez-Mier EA, Sanchez BN, Basu N, et al. Prenatal fluoride exposure and cognitive outcomes in children at 4 and 6–12 years of age in Mexico. Environ Health Perspect. 2017;125:097017.
8. Mahmood S, Rahman M, Biswas SK, Saqueeb SN, Zaman S, Manirujjaman M, et al. Vitamin D and parathyroid hormone status in female garment workers: a case-control study in Bangladesh. Biomed Res Int. 2017;2017:4105375. https://doi.org/10.1155/2017/4105375.
9. Ritu G, Gupta. Ajay. Vitamin D deficiency in india: prevalence, causalities and interventions. Nutrients. 2014;6:729–75. https://doi.org/10.3390/nu6020729.
10. Song SJ, Zhou L, Si S, Liu J, Zhou J, Feng K, et al. The high prevalence of vitamin D deficiency and its related maternal factors in pregnant women in Beijing. PLoS ONE 2013;8:e85081. https://doi.org/10.1371/journal.pone.0085081.
11. Cho WI, Yu HW, Chung HR, Shin CH, Yang SW, Choi CW. Clinical and laboratory characteristics of neonatal hypocalcemia. Ann Pediatr Endocrinol Metab. 2015;20:86–91. https://doi.org/10.6065/apem.2015.20.2.86.
12. Simmonds CS, Karsenty G, Karaplis AC, Christopher S. Kovacs parathyroid hormone regulates fetal-placental mineral homeostasis. J Bone Min Res. 2010;25:594–605. https://doi.org/10.1359/jbmr.090825.
13. Peters JH, Greenman L, Danowski TS. Beneficial effects of calcium chloride in fluoride poisoning. Fed Proc.1948;7:92.
14. Ba Y, Zhu JY, Yang YJ, Yu B, Huang H, Wang G, et al. Serum calciotropic hormone levels, and dental fluorosis in children exposed to different concentrations of fluoride and iodine in drinking water. Chin Med J. 2010;123:675–9.
15. Barbier O, Arreola-Mendoza L, Razo LMD. Molecular mechanisms of fluoride toxicity. Chem Biol Interact. 2010;188:319–33. https://doi.org/10.1016/j.cbi.2010.07.011.
17. Bharathi AV, Kurpad AV, Thomas T, Yusuf S, Saraswathi G, Vaz M. Development of food frequency questionnaires and a nutrient database for the Prospective Urban and Rural Epidemiological (PURE) pilot study in South India: Methodological issues. Asia Pac J Clin Nutr. 2008;17:178–85.
18. Grimaldo M, Borja-Aburto VH, Ramirez AL, Ponce M, Rosas M, Diaz-Barriga F. Endemic fluorosis in San Luis Potosi, Mexico. I. Identification of risk factors associated with human exposure to fluoride. Environ Res. 1995;68:25–30. https://doi.org/10.1006/enrs.1995.1004.
19. Ahmed I, Rafique T, Hasan SK, Khan N, Khan MH, Usmani TH. Correlation of fluoride in drinking water with urine,blood plasma, and serum fluoride levels of people consuming high and low fluoride drinking water in Pakistan. Fluoride. 2012;45:336–40.
20. Lizet J-Y, José de Jesús M-S, Nelly M-F, Enrique G, Diana Olivia R-A, Olga Dania L-G et al. Association between urine fluoride and dental fluorosis as a toxicity factor in a rural community in the State of San Luis Potosi. Scientific World J. 2015. 1–5. https://doi.org/10.1155/2015/647184.
21. Till C, Green R, Grundy JG, Hornung R, Neufeld R, Angeles Martinez-Mier E, et al. Community water fluoridation and urinary fluoride concentrations in a national sample of pregnant women in Canada. Environ Health Perspect. 2018;126:107001 https://doi.org/10.1289/EHP3546.
22. Opydo-Szymaczek J, Borysewicz-Lewickaa M. Urinary fluoride levels for assessment of fluoride exposure of pregnant women in Poznan, Poland. Fluoride. 2005;38:312–7.
23. Kumar S, Lata S, Yadav J, Yadav JP. Relationship between water, urine and serum fluoride and fluorosis in school children of Jhajjar District, Haryana, India. Appl water Sci.2017;7:3377–84.
24. Marwaha RK, Tandon N, Chopra S, Agarwal N, Garg MK, Sharma B, et al. Vitamin D status in pregnant Indian women across trimesters and different seasons and its correlation with neonatal serum 25-hydroxyvitamin D levels. Br J Nutr. 2011;106:1383–9.
25. Sahu M, Das V, Aggarwal A, Rawat V, Saxena P, Bhatia V. Vitamin D replacement in pregnant women in rural north India: a pilot study. Eur. J Clin Nutr. 2009;63:1157–9.
26. Kalra P, Das V, Agarwal A, Kumar M, Ramesh V, Bhatia E, et al. Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant. Br J Nutr. 2012;108:1052–8.
27. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V. High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India. Am J Clin Nutr. 2005;81:1060–4.
28. Sheetal S, Ashok K, Sudha P, Shashi S. Current scenario of vitamin D status during pregnancy in north Indian population. J Obstet Gynecol India. 2016;66:93–100.
29. Sahu M, Bhatia V, Aggarwal A, Rawat V, Saxena P, Pandey A, et al. Vitamin D deficiency in rural girls and pregnant women despite abundant sunshine in Northern India. Clin Endocrinol. 2009;70:680–4. https://doi.org/10.1111/j.1365-2265.2008.03360.x.
30. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V. High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India. Am J Clin Nutr. 2005;81:1060–4.
31. Bhalala U, Desai M, Parekh P, Mokal R, Chheda B. Subclinical hypovitaminosis D among exclusively breastfed young infants. Indian Pediatrics. 2007;44:897–901.
32. Farrant HJ, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, et al. Vitamin D insufficiency is common in indian mothers but is not associated with gestational diabetes or variation in newborn size. Eur J Clin Nutr. 2009;63:646–52. https://doi.org/10.1038/ejcn.2008.14.
33. Agarwal N, Arya SC. Vitamin D3 levels in pregnant women and newborns at a private tertiary care hospital in Delhi, India. Int J Gynecol Obstet. 2011;113:240–1. https://doi.org/10.1016/j.ijgo.2011.01.005.
34. Krishnaveni GV, Veena SR, Winder NR, Hill JC, Noonan K, Boucher BJ, et al. Maternal vitamin D status during pregnancy and body composition and cardiovascular risk markers in indian children: the Mysore Parthenon Study. Am J Clin Nutr. 2011;93:628–35. https://doi.org/10.3945/ajcn.110.003921.
35. Whitford GM, Pashley DH, Garman RH. Effects of fluoride on structure and function of canine gastric mucosa. Dig Dis Sci. 1997;42:2146–55.
36. Sharma JB, Sharma S, Usha BR, Yadav M, Kumar S, Mukhopadhyay AK. Cross-sectional study of serum parathyroid hormone level in high-risk pregnancies as compared to nonpregnant control. Indian J Endocr Metab. 2016;20:92–6.
37. Chen CJ, Anast CS, Brown EM. Effects of fluoride on parathyroid hormone secretion and intracellular second messengers in bovine parathyroid cells. J Bone Min Res. 1988;3:279–88.
38. Frglich A, Rudnicki M, Fischer-Rasmussen W, Olofsson K. Serum concentrations of intact parathyroid hormone during late human pregnancy: a longitudinal study. Eur J Obstet Gynecol Reprod Biol. 1991;42:85–7.
39. Megan L, Mulligan BA, Shaili K, Felton MD, Amy E, Riek MD, et al. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol. 2010;202:429.e1–e9. https://doi.org/10.1016/j.ajog.2009.09.002.
40. Verity CM, Burman D, Beadle PC, Holton JB, Morris Audrey. Seasonal changes in perinatal vitamin D metabolism: maternal and cord blood biochemistry in normal pregnancies. Arch Dis Child.1981;56:943–8.
41. Yamaga A, Taga M, Hashimoto S, Ota C. Comparison of bone metabolic markers between maternal and cord blood. Horm Res 1999;51:277–9.
This research was funded by Indian Council of Medical Research (ICMR), India.