Intersecting and intricacy pathways of Vitamin D and Fluoride in obesity.

Introduction

Fluoride is a highly reactive, electronegative element. Fluorosis is a sequela following high fluoride exposure viz, consumption of drinking water with high fluoride. Fluoride toxicity in water is a serious global health concern, including India.^[1] Fluorosis endemicity impairs health of humans and animals.^[2] It is estimated that 66.6 million population across 17 states in India are at risk of fluorosis.^[3] Around 90% of fluoride is taken up through gastrointestinal tract, and only 10% is excreted through feces. Ninety-nine per cent of fluoride accumulates in bones and teeth, and only 1% is found in soft tissues.^[3] Intersecting and intricacy pathways, biochemical variables and fluoride in obesity and its impact are yet to be studied. Obesity, by definition, is body mass index (BMI) >25; may be attributed to lifestyle modifications, dietary habits and genetic factors.^[4] Studies implicating vitamin D and obesity need to be established.^[5] Limited information about fluoride on metabolomics, genomics and proteomics and its impact on the health and society has created interest in us to find effect of fluoride and vitamin D in obese individuals. Fluoride inhibits enolase enzyme that plays a critical role in regulation of glycolysis. Inhibition of enolase will lead to increase in substrate of glycolysis with an unaltered glucose value. Point that needs to be mentioned here is that the alcohol products derived from glucose have got impact on various other metabolic pathways with an intricacy linked to vitamin D metabolism.

It is hypothesized that high fluoride exposure is one of the aetiological factors for obesity and its related complications.

Materials and Method

Study design

Ours is a retrospective study with a sample size of n = 70.

Sample size is calculated with a 95% confidence interval, 5% Margin of error, and 50% response distribution.

Study is conducted at R. L Jalapa Hospital, attached to Sri Devaraj Urs Medical College, Constituent of Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Karnataka. Institutional Ethics Committee approved study vide No: SDUAHER/KLR/R&D/CEC/F/NF/40/2024-25. Standard procedure and precautions were followed at each step during collection of blood samples and processing. Chemistries were analyzed by Ortho Vitros 5600 dry chemistry analyzer, making use of the principle of reflectance photometry. Vitamin D was analyzed by electrochemiluminescence immunoassay. Fluoride was analyzed by Ion ion-selective electrode.

Inclusion and Exclusion Criteria

• Present study included subjects with obesity, who were exposed to high fluoride content.
• Subjects with non-obesity despite being exposed to high fluoride are excluded from the study.

Variables

Statistical analysis was conducted by using a licensed version of SPSS 23.0 (IBM) (Kolar, Karnataka, India).

Paired student t-test and Pearson correlation were used to find the significance, and a p value < 0.05 was considered statistically significant.

Results and Discussion

p value was significant for calcium in the body mass index (BMI) 25–29 group, as depicted in Table 1 who constituted 58 study subjects, approximately around 83% and in the BMI >35 group with n = 3 (4%). To our surprise, calcium was not statistically significant in the BMI group of 30–34, with n = 9 constituting around 13%. This clearly shows that calcium has an impact on lower but acceptable BMI and on the population with a BMI >35. The congener molecule linked with calcium vis-à-vis vitamin D was not statistically significant in any of the three frequency-distributed study groups. Indirectly giving a hint that vitamin-D may act as an autonomous molecule in various metabolic regulations.

Fluoride exhibits a strong affinity for hydrogen bonds [H bonds], hydroxyl (-OH) and amine (-NH) groups. Fluoride (F^–) forms stable complexes with multivalent metal ions such as aluminum (Al³⁺), iron (Fe³⁺) and magnesium (Mg²⁺).^[6] Excessive fluoride levels in drinking water exceeding 1.5 ppm pose risks to human health, dental decay, osteoporosis, renal damage, neurological and muscular impairments.^[7] Studies linking fluoride with omics of fluoride-BMI are inconclusive or not clear. In-house studies conducted by Shashidhar et al.^[8] have not observed a significant correlation between fluoride and BMI. In our present study, as depicted in Table 2a, we observed a positive correlation between serum fluoride and BMI, which may be attributed to the high circulating fluoride levels. Our study findings are consistent with Deepa Singh et al.^[9] Since BMI is calculated by weight in Kg/height in m² as depicted in the Table 1 we have categorized study subjects into three categories based on the BMI into 25–29, 30–34 and >35 with a frequency distribution of five and majority of our study subjects were in the BMI group of 25–29 (n = 58) approximately 83%. In addition to fluoride and vitamin D, we also tried to correlate lipoproteins and serum lipids. We observed a positive correlation between total cholesterol and high-density lipoproteins (HDL) levels as depicted in Table 2a may be due to the calcitriol form of vitamin D in adiposities.

Our observation showed a direct correlation of TC with vitamin D, highlighting both the values are less we didn’t observed any significant correlation in Table 2b. Since the study area Kolar district, is a temperate zone with scanty rainfall, bore hole water table beyond 1,300 feet and fluoride endemic; to what extent the vitamin D synthesis and its circulating levels are lower needs to be addressed. In our present study the mean ± standard deviation of vitamin D in males (20.6 ± and females (17.7 ± 6.62) that are consistent with study findings conducted by Mahendra Kumar Verma et al.,^[3] who has observed that fluoride inhibits vitamin D. The same aetiopathogenesis and metabolomics might have played a significant role for the low vitamin D levels.

In study subjects, we have observed that obesity is linked to nutritional deficiencies such as micronutrients, vitamins, and minerals.^[10] The major congener mineral for vitamin D is calcium. It has been documented that calcium absorption in stomach depends on presence of active vitamin D, which is critical for maintenance of calcium-phosphorus balance and energy metabolism.^[10] Calcium plays a dual role by promoting fat synthesis through de-novo lipogenesis.^[10] As this wonder mineral, calcium and sunshine hormone vitamin D are interlinked, the intersecting and intricacy pathways of vitamin D and fluoride in obesity cannot be neglected. In our study, as depicted in the Tables 2c and 3a and 3c we observed a correlation of Fluoride with gender, age, BMI, calcium and HDL, where adipose tissue serves as a storage site for vitamin D, affecting calcium homeostasis and energy metabolism that are similar with study findings of Bashar Alzohily et al.^[5] In Table 3b we had not observed any significant correlation individuals with obesity, vitamin D supplementation leads to accumulation of fat in liver and adipose tissue, which influences metabolic processes such as leptin-to-adiponectin ratio, reducing inflammation and altering lipid metabolism may lead to Metabolic dysfunction associated fatty liver disease (MAFLD).^[11] Additionally, dietary deficiency of calcium has a negative impact on carbohydrate and lipid metabolism, with a resultant increased body fat.^[10]

Vitamin D plays a key role in regulating metabolic activity in non-skeletal organs, indirectly affecting hepatic lipid metabolism, thus reducing total cholesterol, triglycerides, and low-density lipoprotein.^[10] In fluoride-endemic areas, overexposure to fluoride is considered a significant risk factor for vitamin D deficiency with a triangular competition between fluoride, calcium – and vitamin D. Remedial measures to prevent the toxicity of ions such as fluoride, nitrate, arsenic, iron, etc., which contribute to salinity of water need to addressed. This can be overcome by drinking alkaline water or RO water without affecting the filtration of essential minerals and micro minerals, which are required for enzyme activities.^[12] Any neglect in the filtration out of these essential minerals, in addition to the fluoride and arsenical, has got impact on the Metallo enzymes with a resultant effect on carbohydrate, lipids, proteins, heam and nucleic acid metabolism even without sparing the other mineral as well as vitamin metabolic pathways.

Conclusion

Vitamin D – fluoride – calcium– minerals intersect in various metabolic pathways and have intricacies with the omics. However, to draw a line in conclusion in-depth omics – studies with larger population size implicating the physiological and pathological process of human health and disease need to be considered in high fluoride endemic areas.

Availability of data and materials

Data is available with the corresponding authors.

Author’s contributions

Ms. P.S.R: Sample collection, analysis, article drafting

Dr. SKN: Subject recruitment and article review

Dr. MUL: Statistical analysis and interpretation

Dr. SCS: Sample collection.

Ethics approval and consent to participate

Central ethics committee of the Academy approved the study as per the declaration of HelsinkiNo: SDUAHER/KLR/R&D/CEC/F/NF/40/2024-25.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.