Vitamin D and its Effect on Periodontium

ABSTRACT

Vitamin D plays an essential role in maintaining the calcium levels in the bone. They go through various processes to be activated. The activated Vitamin plays most of the functions. Thus, is an essential component for the working of the human body. Periodontitis is the inflammation of the supporting structures of the tooth. Vitamin D plays an important role in its healing, functioning and maintenance. Thus, co-ordination and adequate levels of vitamin D is important for maintaining and proper functioning of the periodontium.

Introduction

Every working object requires some kind of energy to function, whether it’s a machine, a single cell, microorganism or a complicated human body. The energy for the working of a human body is derived from an essential component that is nutrition. According to Nutrition and Diet Therapy Reference Dictionary it is defined as science of food, the nutrients and other substances therein, their action, interaction and balance in relation to health and disease, and the processes by which the organism ingests, absorbs, transports, utilizes and excretes food substances.¹ In simple word nutrition is a composition of various nutrients. Out of which some are essentially needed by the body for growth and development, which are obtained from food that we take because they are either not produced or are produced in a very small quantity.
These are broadly classified as macronutrients that include protein, carbohydrate and fats respectively and micronutrients that include vitamins and minerals. Another essential component required is water. Thus, there are 6 essential nutrients of the body. Vitamins, are the organic compounds that are required for the body sustenance.² There are 13 known vitamins available. They can either be water or fat soluble. The fat-soluble vitamins are stored in the fatty tissue of the body and liver and are namely A, D, E and K. These vitamins have longer substantivity in the body as compared to water soluble vitamins. The water-soluble vitamins are namely C and B.

Formation and Activation of Vitamin D

Vitamin D is a fat-soluble that is produced endogenously in the skin following exposure to sunlight and is also taken by exogenous sources.³ The Vitamin D obtained from these sources are biologically inert. It is activated by the process of hydroxylation which occurs twice. First reaction takes places in the liver which coverts vitamin D to 25-hydroxyvitamin D[25(OH)D], also known as calcidiol. Second reaction takes place in kidney in which physiologically active form 1,25-dihydroxyvitamin D [1,25(OH)₂D], also known as calcitriol. The first step in the formation of vitamin D is generally regulated by the amount of vitamin in the blood. Whereas, the second step is catalysed by 1-alpha-hydroxylase which is regulated by parathyroid hormone (PTH) phosphorous blood levels.⁵ It is transferred in the body by Vitamin D binding protein.⁶

Physiological actions of Vitamin D

It promotes the absorption of calcium and phosphorous maintaining normal mineralisation of the bone.⁷ Thus, helps in bone growth and remodelling by the regulation of RANKL (Receptor activator of nuclear factor kappa-B ligand) and OPG (Osteoprotegerin) by increasing and down regulating their expression respectively.^8-11 Baldock et al¹² did a study in mice and reported a reduction in OPG expression. Kitazwa et al¹³ studied the relation of Vitamin D and RANKL and concluded that Vitamin D increases the expression of RANKL and thus promoting osteoclastogenesis. However, Kondo et al¹⁰ reported that OPG level can be brought back to normal if it is exposed to vitamin D for a longer period of time. Evidently, longer exposure can facilitate osteoblast proliferation and differentiation by gene regulation.
It has other potent roles in the body as well that includes its anti-inflammatory actions. It inhibits the MAPK gene that leads to reduction of TNF-α (Tumour necrosis factor-α) and IL-6 (Interleukin) by mononuclear cells.¹⁴ It also reduces the production of IL-7, which has an important role in many inflammatory diseases such as periodontitis. It increases the production of IL-4 which is an anti-inflammatory cytokine.¹⁵ In addition it reduces the production of prostaglandin by inhibiting cycloxygenease-2 as well as activation of pro-inflammatory molecule by reducing nuclear kappa B.¹⁶ It upregulates the expression of IL-8 by activating the expression of trigger receptor expressed on myeloid cells (TREM) in gingival epithelium cells.¹⁷
Innate as well as adaptive immunity is also affected by it. Toll-like receptors which are essential component of innate immunity functions by induction of antimicrobial peptides (AMPs) such as cathelicidin and reactive oxygen species that act against bacteria. The expression of cathelicidin is induced by activated Vitamin D form. However, it has an inhibitory effect on adaptive immunity by decreasing the maturity of dendritic cells. It also inhibits development of Th1 cells which produce IFN-ϒ and IL-2, and Th17 cells producing IL-17. Also, very promising data has been obtained from animal and cell culture studies that it can prevent cancer development or may even lead to decreased metastasis.¹⁸

Daily requirements and sources

Recommended dietary allowance for vitamin D varies according to the age. For age range of 0-12 months it is 400 IU for males as well females. For 1-70 years it is 600 IU. Whereas it increases to 800 IU for >70 years of age for males as well as females. The best dietary source includes salmon, tuna and mackerel fish and fish liver oils. Small amount is present in beef liver, cheese, and egg yolks. In the 1930s, a milk fortification program was implemented in the United States. Both the United States and Canada mandate the fortification of infant formula with vitamin D: 40–100 IU/100 kcal in the United States and 40–80 IU/100 kcal in Canada.⁴

Outcomes of Deficiency of Vitamin D

Deficiency of vitamin D can lead to rickets in children and osteoporosis and osteopenia in adults. Individuals are generally more prone to fractures usually due to negative calcium balance, impaired bone mineralisation. Chapuy et al,¹⁹ did a study and concluded that supplementation with vitamin D3 and calcium reduces the risk of fractures and other nonvertebral fractures. Liu PT et al²⁰ concluded that annual injection of vitamin D can result in reduced fracture in elders. It may be mainly due to decreased exposure to sunlight as well as decreased dietary intake. Some other reasons that can cause deficiency included genetic defects in the Vitamin D receptors, kidney or liver dysfunction that can lead to decreased generation of activated form, sunscreens that have SPF greater than 8 effectively blocks synthesis in the skin, increased amount of melanin that is people with dark skin have decreased amount of vitamin.⁴

Vitamin D and periodontium

The active form that is 1, 25-(OH)₂D₃ positively regulates the various genes through 1-α-hydroxylase enzymes which encodes for proteins responsible for tight adherence and gap junctions seen in the epithelium of the periodontium. Thus, improving the cell barrier as well as cell to cell communication. Due to its effect on the immune cells that is mediated by toll like receptors it can have antibacterial effect on periodontal pathogens in turn reducing the chances of gingivitis or periodontitis. The gene that regulates the production of cathelicidin is hCAP-18. Liu et al20 did a study and concluded that cathelicidin is required for the 1, 25D₃-triggered antimicrobial activity against intracellular M. tuberculosis. Similarly, Gombart et al²¹ related the function of active form of vitamin and VDR in regulation of primate innate immunity. McMahon et al²² demonstrated increased antimicrobial activity of Vitamin D against periodontal pathogen Aggregatibacter actinomycetemcomitans.

Vitamin D and Bone loss

The deficiency of Vitamin D leads to osteoporosis which is a multifactorial disease just as periodontal disease.²³ Vitamin D as is evident is responsible for calcium absorption and remodelling of bone. This also affects the oral bone loss. It has been attempted to establish a link between generalised bone loss and oral bone loss and mechanism linking them. However, the results have been contradictory. Jeffcoat et al²⁴ did a systematic review on the relation between systemic and oral bone loss maximum results were in favour of the relationship. Similarly, Inagaki et al²⁵ showed positive relation between decreased bone density due to osteoporosis and bone loss in few teeth.
However, most of the studies concluded that there are not sufficient data to establish this fact or the exact mechanism is not defined. As stated, before that both the diseases are multifactorial hence the various factors that play a role is their progression is not known. Factors such as age, environmental factors, genetics, normal flora of the body, sex also play a role in their pathogenesis. Hence, the exact mechanism of these factors playing a role and systemic effect of bone loss on oral bone loss could not be established. Hence, well controlled studies with adequate sample size, different populations along with other factors, should be done to establish a well-documented fact. Elders et al,₂₆ established that osteoporosis had no significant effect on periodontal disease which was in accordance with the study done by Klemetti et al27.

Inflammation and periodontal health

The cells that play an important role in inflammation are macrophages. Although present in health too. They are the first line of defence in case of any injury or infection. They help maintain balance between availability of antigen and their subsequent degradation by various processes.²⁸ In the blood they are generally present in the form of monocytes which are activated to macrophage at the inflammation sites. They work by the release of pro-inflammatory cells that is interleukins, interferons, prostaglandins.
Active form of vitamin D induces monocytes to be converted to macrophages which express the enzyme that can increase the lysosomal activity along with phagocytosis and also increase the production of 1,25-(OH)2D3 that is 1 α-hydroxylase. The activated form also supresses the synthesis of IL-1, IL-6, TNF-α by decreasing the formation of m-RNA for these products. It also leads to dose-dependent inhibition of Lipopolysaccharide induced by p38 phosphorylation at physiologic concentrations.²⁹ Hence, they can be utilized for the management of periodontitis.
Miley et al³⁰ concluded that subjects on Vitamin D therapy had lesser probing depths as compared to ones without it. Similarly, Garcia et al³¹ showed positive effect of Vitamin D on the periodontal health. Rosa et al,³² demonstrated that it helps in the conversion of monocytes to macrophages along with regulation of calcium levels in the body. Krutzik et al³³ did a study and demonstrated the TLR2/1-induced monocyte differentiation to macrophages.
Dietrich et al³⁴ study established a inverse relationship between the attachment loss and the vitamin D levels that is lower amount of Vitamin D caused more amount of bone loss. He associated these findings to the anti-inflammatory actions of the vitamin. In his study participants experienced 20% less bleeding on probing than with those having lower levels of the Vitamin. Thus, it can evidently reduce the risk of gingivitis as well as periodontitis. It is attributing to these qualities it can be correctly stated as perio-protective mineral of the body. The association of VDR-gene with bone loss, periodontal diseases finally leading to tooth loss have further confirmed these mechanisms.³³ Thus the daily intake of 800 IU/day seems to be adequate in maintaining the periodontal health as well.

Vitamin D and Wound healing

Periodontitis, is characterised by bone loss which is the inflammatory response owing to the bacterial load present in the tissues. Integral role of vitamin D in immunity and inflammation has increased the bone maintenance and immunity. Thus, adequate amount of Vitamin D can be beneficial but the deficiency of it could lead to negative impact on the periodontium. Thus, biological maintenance of the vitamin D can be beneficial for the biological maintenance of the periodontium as well.
The effect of Parathyroid hormone, calcium and vitamin D supplements showed positive effect on the postsurgical healing was shown efficiently by Bashutski et al.³⁴ The treatment of periodontal diseases can be either surgical or non-surgical. The non-surgical treatment comprises of scaling and root planing. Whereas, the surgical treatment includes flap surgeries. The outcome of these modalities can be greatly affected by the vitamin D amounts. The anti-inflammatory actions and its effect on the bone can help promoting the wound healing as well as tissue regeneration which is essential for better periodontal outcomes.
Bashkushti et al³⁵ in another 6 weeks experimental study on the treatment of intrabony defects showed the encouraging effects of Vitamin D on the outcome of the open flap debridement surgery along with the PTH, calcium and Vitamin substitutes. Hence, it can be aptly concluded that Vitamin D promotes healing and can be a great asset for periodontal regeneration.

Conclusion

The Multitudinous researches done in the context of Vitamin D have evidently supported the beneficial effects that it renders not only for the overall well-being but also for the oral health of an individual. Although, many studies have proved the inverse relationship between osteoporosis/low bone mass may be a threat for periodontal diseases too still further studies are needed to determine the pathogenesis for the same. Besides the effects on the oral environment enough evidence has been provided for its clinical implications and its importance in other sectors such as cardiovascular diseases, diabetes, arthritis and cancer. Vitamin D can play a significant role in heightening the immunity of an individual by strengthening the physical barriers of the cell. Thus, it can be aptly named as perio-protective for the human body. However, still more exhausting and specific studies need to be done in this field for utilizing the beneficial effects of the Vitamin.

References