A Positive Correlation Between Vitamin D and Fluoride in Patient

Tripathi et al . Int J Gastroenterol Hepatol Transpl Nutr 2019;4 (iii):1-5 ISSN 2455–9393

International Journal of Gastroenterology, Herpetology, Transplant & Nutrition

Original A rt i c l e

A Positive Correlation between Vitamin D and Fluoride in patient with fluorosis Mahendra Kumar Verma1, Dushyant Singh Chauhan2,5, Deepak Nathiya3, Sandeep Tripathi4,5, Prakash Aswani4

1Nims College of Paramedical Technology, ABSTRACT 2Nims Institute of Engineering & Technology 3Nims Institute of Pharmacy, 4National Institute Fluoride toxicity is a burgeoning problem in worldwide. It is a serious of Medical Science & Research, 5National Referral Centre for Fluoride Poisoning in India, health problem of the population living in high fluoride region. Many Nims University Rajasthan, Jaipur India experimental and clinical studies have been reported that the fluoride

induces deformities in bones and deterioration in skeletal system but exact mechanism of action is still unknown. In the present study, 50

male subject were recruited from the orthopedic OPD at National Address for Correspondence Institute of Medical Sciences & Research Hospital, Nims University Dr. Sandeep Tripathi Email: [email protected] Rajasthan, Jaipur, India. The age matched controls were selected from the area where fluoride content was less than 1.5 ppm. Serum fluoride Access this article online and 25-Hydroxy vitamin D (25 OHD) were estimated in both subject and QR Code Website: controls. Significant (p<0.001) reduction was observed in the 25 OHD www.ijrpsonline.com while the concentration serum fluoride was found to be significantly (p<0.001) elevated as compared with their respective controls. It is

observed that a positive correlation (r=0.738; p<0.001) between 25OHD

and serum fluoride. On the basis of results, it may conclude that correlation of the serum fluoride and 25OHD may be used as early marker for the detection of fluorosis. However, a deep study in rodent model may be required to explore the mechanism.

Key words: Fluorosis; 25 OHD, Bone deformities

INTRODUCTION and human health (Tripathi et al., 2015; Grandjean, 2019). An estimated that 66.6 The fluoride contaminated drinking water is million people (17 states in India) are at risk common cause of Fluorosis. It is one of the of acquiring Fluorosis. In Rajasthan, people manifestations of chronic poisoning from of almost all districts are presently long-term exposure to high levels of ﬂuoride consuming fluoride greater than permissible (Chauhan et al., 2014; Mohammad et al., limit. 2017), and is a serious health problem in Acute or chronic exposure to many parts of the world where drinking fluoride in the population it may cause water contains more than 1–1.5-ppm of various pathological changes in skeletal ﬂuoride (WHO, 1984). The endemic system. It has been well documented that fluorosis is widespread in many parts of the excessive fluoride intake on bones and teeth world and often critically impairs the animal of human. It is mainly characterized by

1 Tripathi et al . Int J Gastroenterol Hepatol Transpl Nutr 2019;4 (iii):1-5 ISSN 2455–9393 dental mottling as well as skeletal its correlation with Serum fluoride and it manifestations such as pain and stiffness of may be used as an early marker for the joints; crippling deformities, osteosclerosis detection of Fluorosis. and osteoporosis other Clinical symptom may include leading to crippling life of a MATERIAL AND METHODS person. Person may exhibit low back pain, Subject selection joint pains, myalgia and person may also In the present study, 50 male fluorosis suffer from various deformities of axial patients (age 37 ± 4.2) were selected after skeleton as well as limb deformities (Wang the performance of Physical test and serum et al., 1994; Tiwari et al., 2014). fluoride levels in subjects. The age matched There is multiple mechanism of the controls were selected from the area where fluoride that exerts its toxic effects on the fluoride content was less than 1.5 ppm. The body; the primary phenomenon which is inclusion criteria of the subject are persons involved in the neurotoxicity of fluoride having fluorosis confirmed by consultant through the generation of free radical and and they are residing in fluoride endemic oxidative stresses (Chauhan et al., 2014). area since last 10 years, while the exclusion Fluoride is highly reactive with the criteria are apparently not healthy adult were molecules due its high electronegativity (F– excluded and having other degenerative and forms), strong affinity with hydrogen bonds infectious diseases. An approval to carry out (especially e –OH and –NH moieties). the study was obtained from the Institutional Fluoride has potent capacity to form stable Human Ethical Committee of the subjects complexes with multivalent metal cations and controls were given a full explanation like Al3+, Fe3+, and Mg2+ (Chinoy et al, about the purpose of the study and assurance 2003; Chlubek et al, 2003). about the confidentiality of the information It is documented that Ca and 25 and that the participation was optional. OHD may control the severity of fluoride Before the study, the consent of the subjects toxicity during the continue exposure of the and control were taken. fluoride. It is recently reported by Patel and Biochemical Assessment associates (2017) that; adequate calcium and After clinical examination of subjects and vitamin D intake may enhance the controls, 5.0 ml of blood sample was drawn absorption and retention of fluoride and under complete aseptic condition in simple consequently, affecting the hard tissues vial and was allowed to clot at room (bone and teeth). Moreover, research on temperature. The separated serum was used reversal of fluorosis shows that adequate to measure serum fluoride levels using Vitamin D status enhances calcium specific fluoride electrode (¬¬¬¬Thermo absorption and retention and thus directly Fischer, Singapore). The plasma baseline affects the absorption of fluoride ions 25(OH) vitamin D levels were measured by (Teotia 1999; Bawaskar and Bawaskar high performance liquid Chromatography 2006) (Loo and Brien 1983). Keeping in view the paucity of information in relation to fluoride and its RESULTS causing bone deformities in population There was no statistically significant residing in fluoride endemic areas and its difference between age, sex, marital status, impact on health and society, the present BMI, socio economic status, literacy and study was undertaken. The significance of smoking and alcoholic addition of the this study is to investigate the 25 OHD and control and subject (Table-1). The concentration of serum fluoride was found

2 Tripathi et al . Int J Gastroenterol Hepatol Transpl Nutr 2019;4 (iii):1-5 ISSN 2455–9393 to be significantly (p<0.001) elevated in the subjects. The concentration of serum 25 12 OHD was found to be decreased 10

significantly (p<0.001) in the subject when 8 compared with their respective controls 6

(figure-2). The concentration of hydroxy Vitamin D Vitamin 4 proline were found to incresead markedly y = 9.8541x + 1.4771 R² = 0.738 (P<0.01) in subject than that of controls. The 2 values of the Pearson coefficient were 0 correlated between serum fluoride and 25 0 0.2 0.4 0.6 0.8 1 Serum Fluoride OHD levels of the subjects. The positive Figure 3: The significant positive correlations (r= correlation (r= 0.738, p<0.001) between 0.738; p<0.001) exist between serum fluoride and serum fluoride and 25 OHD were found to 25OHD in the subjects. be significantly (figure -3).

Table-1 Demographic data of Subjects and DISCUSSION

controls Fluorosis is an important public health Control (55) Exposed (50) issues in India and worldwide due to the Age 37.4 ±5.2 35.8 ± 5.1 Sex Male Male excessive contamination of fluoride in Marital Status Married Married drinking water (WHO, 1984). Fluorosis BMI 22.2 ± 1.3 22.8 ± 1.2 caused by excessive limit (>1.5ppm) of Socio-economic Lower (100%) Lower (100%) status fluoride in their drinking water or may be Literacy (H. Sc.) 100 % 100 % other dietary and medical sources (Turkekul Smokers 55% 52% et al., 2020). Dental and skeletal fluorosis is Alcoholic 3.8% 3.3 % being apparent due to the higher (occasionally) (occasionally) Age and BMI are expressed as mean ± SD and others parameters contamination of fluoride in the drinking represented in percentage in control and subjects. water. Skeletal changes may result when

Serum Fluoride (ppm) drinking water content of fluoride exceeds 2

0.4 ppm. In the present study, results of the p<0.001 analysis of the water samples showed that 0.3 the fluoride content in abnormal range in 0.2 serum (Figure-1). The generally accepted average normal serum fluoride value is 0.15 0.1 ppm as found by Singer and Armstrong 0 (1977). Control Subject Figure -1. Concentration of serum fluoride in subject In the present study, the fluoride and control. Data are expressed as mean ± SD concentration increases with the reduced

25 OHD (ng/ml) concentration of 25 OHD. it is found that

p<0.001 50 significantly decreased the level of plasma

40 25(OHD) when compared with its age and

30 sex matched controls. Vitamin D plays significant role to maintain strong 20 mineralized skeleton of the human. Sunlight 10 causes the photo-production of vitamin D3 0 in the skin, which is metabolized Control Subject Figure-2. Concentration of serum 25 OHD in subject sequentially in the liver and kidney to 1,25- and control. Data are expressed as mean ± SD. dihydroxyvitamin D. The main function of

3 Tripathi et al . Int J Gastroenterol Hepatol Transpl Nutr 2019;4 (iii):1-5 ISSN 2455–9393

1,25-dihydroxyvitamin D is to keep the insufficient due to fluorosis (Shills et al., serum calcium and phosphorus content 1999; Singh et al., 2013), 1-hydroxylase within the normal range to maintain enzymes may be active and disruption of essential cellular functions and to promote bone mineralization may occurs (Guyton mineralization of the human skeleton 2007). On the other hand Patel et al., (2017) (Holick, 1996). were not found significant correlation Vitamin D is essential to utilize between fluoride and 25OHD and suggested dietary calcium efficiently. A serum 25 due to lower intake of calcium. Khandare et OHD level of at least 20ng/ml is necessary al., (2005) was also observed that some of to minimally satisfy the body’s vitamin D the children from the high fluoride region requirement, and maintenance of a 25 OHD demonstrated severe bone deformities due to serum level of 30 to 50ng/ml is low serum calcium and vitamin D levels recommended. The deficiency of vitamin D further it supported by Tiwari et al (2014). may cause Rickets and osteomalacia which is the classical symptoms of fluorosis further CONCLUSION it is cause rickets in children by a failure of In conclusion, there is significant association bone tissue and demineralization resulting between chronic exposure to fluorosis and skeletal deformities (Holick 2005). 25-OHD in patients with fluorosis. The low If the level of plasma 25(OH)D level of 25-OHD may increase the risk of decreases below a critical level or when Ca absorption through the intestines is fracture and other skeletal complications.

REFFERNCES

1. Bawaskar, H.S. and Bawaskar, P.H., eds. Vitamin D, 2005; 2 (1) Burlington, Endemic fluorosis in an isolated village in MA: Elsevier. western Maharashtra, India. Tropical 8. Holick MF. Vitamin D and bone health. J doctor, 2006;36(4), pp.221-223. Nutr. 1996 Apr;126(4 Suppl):1159S-64S. 2. Chauhan DS, Tripathi S, Singh VP, Tomar doi: 10.1093/jn/126.suppl_4.1159S. S, Tomar S, Tiwari M. Excessive Fluoride 9. Khandare AL, Harikumar R, Sivakumar Delineating Biochemical Changes in B. Severe bone deformities in young Seminal Plasma: A Case Control Clinical children from vitamin D deficiency and Study. European Acade Res. 2014 ;2(7) fluorosis in Bihar-India. Calcif Tissue Int. :9023-904. 2005 ;76(6):412-8. 3. Chinoy, N. J. "Fluoride stress on 10. Loo JC, Brien R. Analysis of 25-hydroxy antioxidant defence systems." 2003; 138- vitamin D3 in plasma by high- 141. performance liquid chromatography. Res 4. Chlubek D, Poland S. Fluoride and Commun Chem Pathol Pharmacol. oxidative stress. Fluoride. 2003 Nov 1983;41(1):139-48. 1;36(4):217-28. 11. Mohammadi AA, Yousefi M, Yaseri M, 5. Grandjean, P. Developmental fluoride Jalilzadeh M, Mahvi AH. Skeletal neurotoxicity: an updated review. Environ fluorosis in relation to drinking water in Health 18, 110 (2019). rural areas of West Azerbaijan, Iran. 6. Guyton AC (2007): Textbook of Medical Scientific Reports. 2017; 7:17300. Physiology. 11th ed. Philadelphia: W.B. 12. Tiwari M, Tiwari N, Singh V, Chaturvedi Saunders Company, 2007. H, Biophysical and Biochemical Markers 7. Holick MF. Photobiology of vitamin D. of Skeletal Fluorosis, Sch. J. App. Med. In: Feldman D, Pike JW, Glorieux FH, Sci., 2014; 2(3B):991-995.

4 Tripathi et al . Int J Gastroenterol Hepatol Transpl Nutr 2019;4 (iii):1-5 ISSN 2455–9393

13. Patel PP, Patel PA, Zulf MM, Yagnik B, 16. Shills ME, Olson JA, Shike M, et al. Kajale N, Mandlik R, Khadilkar V, (1999): Modern Nutrition in Health and Chiplonkar SA, Phanse S, Patwardhan V, Disease, 1999; 9, Baltimore, Williams & Joshi P. Association of dental and skeletal Williams. fluorosis with calcium intake and serum 17. Singer L, Armstrong WD. Fluoride in vitamin D concentration in adolescents treated sewage and in rain and snow. from a region endemic for fluorosis. Archives of Environmental Health: An Indian journal of endocrinology and International Journal. 1977 Jan metabolism. 2017 Jan;21(1):190. 1;32(1):21-3. 14. Tripathi S, Chauhan DS, Singh VP, Joshi 18. Singh VK, Chauhan DS, Tripathi S, DK and Choudhary M, Age Associated Kumar S, Tiwari M, Gaur V, Tomar A. A Fluoride Induced Ultra Structural and correlation between serum vitamin, Biochemical Changes in Rat Brain, MOJ acetylcholinesterase activity and IQ in Toxicology. 2015;1(5): 1-8. children with excessive endemic fluoride 15. Turkekul R, Arihan SK, Yildirim S, exposure in Rajasthan India. Int J Med Arihan O, Oto G, Ekin S, Yildiz D. Effect Sci. 2013; 1(3) :12-16 of acute and chronic fluoride 19. Wang Y, Yin Y., Gilula, Wilson AJ, administration on Bone histopathology, Endemic fluorosis of the skeleton bone fluoride accumulation, and :Radiographic features in 127 patients. Locomotor activity in an animal model of AJR, 1994;162:93-98. Paleopathological fluorosis, Research 20. WHO, Environmental Health Criteria for report Fluoride, 2020; 53(1 Pt 1):77-89. Fluorosis and Fluoride; World Health Organization, Geneva 1984; 1–136.