Vitamin D Deficiency the Real Causative Factor of Dental Caries in Children –a Narrative Review

INTRODUCTION

Dental caries are a noncommunicable disease. With 2.3 billion people suffering from untreated caries lesions in their permanent dentition, dental caries is still one of the most frequent diseases in the world, despite recent advances in concepts and management strategies.¹ Children still continue to have caries rates as high as 85%.² Several factors play a role in the development of dental caries, including microorganisms, diet, oral hygiene, medical conditions, and lack of vital nutrients, such as vitamin D.^3,4 Unquestionably, nutrition and micronutrients play a role in maintaining oral and dental health. Vitamin D is widely recognised as one of the most significant micronutrients among these nutrients due to its key involvement in bone health and its maintenance of dental structural integrity and health.^5,6 The worldwide prevalence of vitamin D deficiency has resulted in a substantial rise in public knowledge of vitamin D.⁷ 1 billion people are at risk of vitamin D deficiency.^8,9 This incidence is concerning and extremely important for overall health, with a particular emphasis on pregnancy and children. Recent research has revealed the pertinent connection between vitamin D deficiency and dental caries, and the significance of vitamin D deficiency for dental caries has grown in prominence. In light of these recent literature evidence, this review is an attempt to see if vit D deficiency is the real causative factor in dental caries in children.

Methods:

A search in pubmed, scopus, google scholar databases using MeSH terms Vitamin D deficiency, dentalcaries, tooth development, s. mutans were performed and articles from 2000 to 2024 which were published in English were reviewed and 57 publications were chosen for critical evaluation process.

DISCUSSION

Trends in dental caries:

According to the 2002–2003 National Oral Health Survey, the DMFT index score for Indian children was approximately 2, and the prevalence of dental caies rose with age, rising from 51.9% to 63.1% in the 5–15 age range, respectively.¹⁰ In 2021, Pragya Pandey et al. performed a systematic review and meta-analysis which evaluated the pooled prevalence of dental caries in the Indian population, reporting an overall rate of 54.16%. The prevalence was 62% among adults (>18 years) and 52% among children and adolescents (3–18 years), with the highest occurrence (58%) observed in the mixed dentition stage. Regional analysis revealed the western region of India had the greatest prevalence (72%), indicating notable geographic and age-related disparities in caries distribution.¹¹

Vitamin D:

Vitamin D,(vit D) sometimes known as sunshine vitamin, is essential to human biology. Exogenous vitamin D3 from food supplements and endogenous vitamin D3 produced following skin exposure to UVB rays are its two primary sources.^12,13 A deficit in vitamin D is defined as the level of 25-hydroxyvitamin D (25[OH] D) below 20 ng/mL.¹⁴ When 1,25-dihydroxyvitamin D interacts with the vitamin D receptor, intestinal calcium and phosphorus absorption efficiency can increase by up to 40% and 80%, respectively.¹⁵ In reference to a study by Song Y et al., mice with vit D receptor (VDR) mutations show notable anomalies in bone formation and mineralisation, as well as a decrease in Ca absorption efficiency of over 70%.¹⁶ Despite the fact that most Indians reside in regions that receive enough sunlight all year round, vitamin D insufficiency is nevertheless quite prevalent in the country in both sexes and all age groups.^17,18 It is mostly recognised for its essential role in maintaining calcium homeostasis, bone metabolism, and improving skeletal health.¹⁹ This vitamin is essential for maintaining good oral health, and deficiencies have been associated with a number of oral health issues as well as significant changes in the oral cavity, craniofacial structures, and tooth structure, which can lead to enamel hypoplasia, dentinogenesis imperfecta, amelogenesis imperfecta, or increased caries risk.²⁰ Vitamin D has an important effect on odontogenesis. The vitamin D-R complex controls the transcription of genes encoding various structural proteins produced by ondontoblasts (dentin phosphoproteins and dentin syloglycoproteins) and ameloblasts (amelogenins and enamelins), which collectively make up the unmineralized extracellular matrix. In addition to its essential function in the synthesis of dental enamel and dentin, vitamin D deficiency influences the development of both primary and permanent teeth.

Poor levels of vitamin D and prevalence in India:

Several research investigations reported a prevalence of 80% to 90% of vit D deficiency, however the varied from 40% to 99%.²¹ About 490 million people in India lack adequate vitamin D, with children and teenagers accounting for 31% of the total.²² Garima rana et al carried out a secondary analysis of data of Comprehensive National Nutrition Survey 2016-18 to analyze the prevalence and predictors of vitamin D deficiency (VDD) among Indian children and adolescents found that overall prevalence of VDD in preschool children (1-4 years), school age (5-9 years) children, and adolescents (10-19 years) was 13.7%, 18.2%, and 23.9%, respectively.²³ Dental caries was present in 54.16% of Indians overall, with age-specific prevalences of 62% in patients over 18 and 52% in those between the ages of 3 and 18.¹¹ The prevalence of dental caries for both coronal and root surfaces was 51.9% in children aged 5 to 12, 53.8% in children aged 12 to 15, 63.1% in teenagers aged 15 to 16, 80.2% in those aged 35 to 44, and 85.0% in those aged 65 to 74, according to the Pan-Indian National Health Survey, which was conducted in 2004 to evaluate the oral health status in representative age groups.

Vitamin D and associated functions

Mellanby and associates' work in the 1920s and 1930s provided a large portion of the early attention on the connection between vitamin D and dental cavities.²⁴ It has been proposed that serum 25(OH)D influences the development of the tooth bud.²⁵ In addition to supporting tooth growth and mineralisation, vitamin D has significant effects on immune response regulation, salivary function optimisation, and the balance of the oral flora.^26,27,28

Vitamin D receptors (VDRs) are cellular receptors that bind to the active form of vitamin D, facilitating its biological actions. The VDR gene, which encodes this receptor, exhibits several polymorphisms that can influence the receptor’s functional activity. Among the most common VDR gene polymorphisms (VDRP) associated with both oral and systemic diseases are BsmI (rs1544410), TaqI (rs731236), BglI (rs739837), ApaI (rs7975232), and FokI (rs10735810 and rs2228570).^29,30 The vitamin D–VDR complex plays a key role in regulating genomic functions in odontoblasts, ameloblasts, and salivary gland cells, all of which express VDRs. This complex is essential for the formation of oral hard tissues, including dentin and enamel. In addition, it induces the production of antimicrobial peptides (such as cathelicidin) in oral epithelial cells and contributes to the secretion of fluids and electrolytes from the salivary glands, processes that are directly vitamin D–dependent.³¹

Vitamin D And Immunity

The potential role of vitamin D in inducing the innate immunity and improving the body’s resistance against different pathogens is well documented.³² it was indicated that vitamin D derivatives are bactericidal and possess lytic activity against Strep. Mutans and target the bacitracin-associated efflux system.³³ According to experimental research, vitamin D directly affects the salivary glands' ability to secrete fluid and electrolytes. Insufficient levels of vitamin D reduce salivary flow, change its composition by lowering calcium ion levels, and lessen its ability to act as a buffer against organic acids. However, since saliva is the natural flow of minerals required for ongoing tooth remineralisation, a vitamin D deficiency would result in a significant decrease in salivary mineral levels, which would be ineffective in promoting remineralisation and it makes tooth susceptible for caries in the primary and/or permanent dentition.³⁴ A decrease in salivary flow rate modifies the immune system of the oral cavity, causing secretory immunoglobulin A (IgA) to decrease and disrupting the colonisation of normal microbiota.³⁵ By stimulating the production of human cathelicidin (LL-37), which has antibacterial and antiendotoxin properties, in oral epithelial cells, vitamin D affects the immune system. The fact that children with high caries activity have low levels of LL-37 highlights the protein's function as a "guardian of the oral cavity" and the significance of oral health.³⁶ Decreases salivary flow and changes its composition (less calcium ions), lowers the concentration of cathelicidin, and promotes the colonisation of cariogenic bacteria (S. mutans), all of which raise the risk of dental caries.³¹ According to a clinical investigation by Johanna Gyll et al., individuals with vitamin D deficiency had much lower salivary cathelicidin concentrations than patients with normal vitamin D status.³⁷

Role Of Salivary Cathelicidin

AMPs, of which cathelicidin is one, are innate immunity's host defence peptides that combat a variety of oral cariogenic microbes. In addition to having chemotactic qualities and contributing to cellular autophagia, it exhibits cationic and anphiphilic qualities that enable it to depolarise and rupture the bacterial cell membrane.³¹ Ex-vivo study by Nireeksha etal reported Salivary vitamin D levels in the caries-free group 28.56 pg/ml were found to be considerably greater than those in the caries-active group 20.85 pg/ml. According to the results of the LL-37 assay, the salivary LL-37 levels in the caries-free group were 7.07 ng/µl, while those in the caries-active group were 7.05 ng/µl. Individuals in the caries active and caries-free groups had salivary levels of IL-17A and IL-6 of 155.01 ng/ml and 174.20 ng/ml, respectively.This is explained by the fact that protective peptides (LL-37/cathelicidins) are produced after being activated by the TLR2-vitamin D LL-37 mechanism. This process takes place when 1,25(OH)2 D binds to the vitamin D receptor. Anti-inflammatory cells like neutrophils have been shown to have the ability to become more antimicrobial when exposed to LL-37.³⁸

Vitamin D And S. mutans

In vitro study conducted by Marta Picolo aimed to investigate the antimicrobial effects of Cholecalciferol (D3) and Doxercalciferol (D2), against S. mutans and on glycosyltransferase gene expression. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of D3 and D2 for S. mutans were determined which showed the MBCs of D3 and D2 were 83 μg/ml and 166 μg/ml respectively. Both compounds were effective in preventing the local pH drop <5.5 at ≥166 μg/ml in sucrose supplemented cultures. However, the compounds did not inhibit pH drop at MIC values. Notably, D2 upregulated GtfD expression significantly (p < 0.05) and downregulated GtfB and GtfC. suggesting potential therapeutic roles in dental caries prevention.³⁹ An invtro study conducted by Almoudi M.M..,et al to evaluate the antimicrobial effects of the cholecalciferol vitamin D3 against Streptococcus sobrinus and Streptococcus mutans. Strep. sobrinus was more sensitive to vitamin D3 compared to Strep. mutans bacteria. The MIC values of vitamin D3 against Strep. sobrinus and Strep. mutans were 60 μg/ mL and 250 μg/mL respectively whereas the MBC values were 120 μg/mL and 500 μg/mL, respectively. significant changes in the bacterial morphology were observed in treated bacterial cells with vitamin D3 as compared to the untreated control bacteria using SEM. suggested that vitamin D3 has excellent antimicrobial effects against Strep. sobrinus and Strep. mutans and may be considered as a promising compound in the prevention of dental caries in the future.⁴⁰

Vitamin D And Dental Caries

Numerous epidemiologic observational studies, systematic reviews, and meta-analyses of controlled clinical trials have evaluated the strong correlation between vitamin D deficiency and dental caries in children's primary and permanent teeth. "Zizhan Li et al.'s recent systematic review and meta analysis revealed that children with vitamin D insufficiency were 22% more likely to develop dental caries than children with normal vitamin D levels. This suggests that low vitamin D levels could be a potential risk factor for dental caries.⁴¹ Sadeghi et al.'s meta-analysis revealed that, of the VDR polymorphisms examined, the FokI (rs10735810) polymorphism was linked to an increased incidence of dental caries, with the f allele and ff genotype playing a protective effect.⁴² Bahardoust M. et al.'s meta-analysis revealed An elevated risk of dental caries in children can be linked to prenatal vitamin D deficiency, particularly in mothers whose prenatal vitamin D levels are less than 35 nmol/L. Having enough vitamin D during pregnancy can help shield children's teeth from cavities.⁴³ According to a meta-analysis by Ji S et al., children with ECC had lower vitamin D levels than children without caries, and there was a strong correlation between S-ECC and vitamin D. A 25(OH)D level of ≥ 75 nmol/l was optimal for preventing the onset and progression of ECC. Clinicians should therefore consider the early caries development from a systemic perspective as well.⁴⁴ Mahmood, M.K. et al.'s systematic study revealed that dental caries was strongly associated with vitamin D deficiency and that a 3% reduction in dental caries was associated with a 10 nmol/L increase in blood 25(OH)D levels.⁴⁵ A longitudinal study by Børsting T et al. revealed a significant association between the number of affected teeth in offspring with MIH at 7-9 years and inadequate maternal vitamin D (< 50 nmol/l) as evaluated in gestational weeks 18–22.⁴⁶ According to a randomised controlled trial by Arponen H et al., daily supplementation with 10 µg of vitamin D3 appears to be sufficient in the Northern Hemisphere for healthy children under the age of two to ensure good oral health at early school age.⁴⁷ According to a study by Schroth et al. Mothers of children with ECC had considerably lower 25(OH)D levels than mothers of children without caries.⁴⁸ Chhonkar A.,et al study reported case group has a mean serum 25(OH) vitamin D level of 12.19 ng/mL and the control group has a mean serum 25(OH) vitamin D level of 20.11 ng/mL.⁴⁹

Vitamin D And Development Of Teeth

Uncontrolled vitamin D levels can disrupt normal tooth growth and mineralisation, resulting in enamel hypoplasia, dentin hypomineralization, and "rachitic teeth".^50,20 Regardless of foetal genetic disorders, maternal 25(OH)D levels can influence deciduous dentition.⁴⁸ Vitamin D levels in the foetal serum circulation follow maternal levels and can be used as a surrogate marker for the foetus.⁵¹ As a result, if the mother's 25(OH)D levels become uneven, the child's health, particularly dental development, may suffer directly or indirectly.⁵² The pattern of mineralisation abnormalities in growing teeth varies according to the gestational period during which maternal vitamin D insufficiency develops. Defects in the incisal, middle, and cervical thirds of the dental crown are associated with deficiency between 12-16 weeks, 20-32 weeks, and 36-40 weeks of gestation, respectively. In a randomized controlled trial, Reed et al. found that pregnant women with serum vitamin D levels below 15 ng/mL had a 14% higher risk of enamel defects in their children’s deciduous teeth compared to those with sufficient vitamin D levels.⁵³ The possible preventive effect of vitamin D for enamel defects was further supported by Nørrisgaard et al.'s RCT, which found that high-dose vitamin D supplementation during pregnancy was associated with a 50% decreased risk of enamel malformations in the newborn.⁵⁴

According to the American Academy of Pediatrics (AAP), the U.S. Endocrine Society, and ESPGHAN, the recommended daily intake of vitamin D is at least 400 IU for children aged 0–1 year and 600 IU for those aged 1–18 years. It is advised that a daily oral supplement of 400 IU cholecalciferol be initiated soon after birth and maintained throughout the first year of life to ensure an adequate vitamin D status.^55,56,57

CONCLUSION

Vitamin D plays a vital role in maintaining oral health by regulating calcium and phosphate metabolism, promoting tooth mineralization, and supporting immune defense within the oral cavity. Deficiency in vitamin D has been increasingly linked to a higher risk of dental caries, enamel hypoplasia, and other developmental defects in both primary and permanent dentitions. Despite growing evidence supporting this association, current literature still presents inconsistencies due to variations in study design, sample size, population characteristics, and differing thresholds for defining vitamin D deficiency. Moreover, the causal relationship between maternal or childhood vitamin D levels and caries susceptibility remains to be clearly established. Future research should focus on well-designed longitudinal and interventional studies to elucidate the dose–response relationship, critical periods of deficiency, and the potential benefits of supplementation in reducing caries risk. Strengthening the evidence base in this area will be essential for developing preventive guidelines and public health strategies aimed at improving oral and systemic health outcomes. Immediate action is necessary to address these worldwide issues. Campaigns for oral health education that raise public knowledge of the value of vitamin D for oral health are strongly advised. Inspite of all the efforts dental caries is still chronic disease in children, hence the measures for control dental caries should include managing the vitamin D deficiency.

REFERENCES