In CHAPTER 2 research is described that studied the relationship between plasma vitamin C levels and the severity of periodontitis in the above mentioned . More; Year: ; Title: Java project on periodontal diseases: the relationship between vitamin C and the severity of periodontitis; Journal: Journal of Clinical. Chapter 2. Java Project on Periodontal Diseases. The Relationship between Vitamin C and the Severity of Periodontitis. Amaliya. 1,2., Timmerman, M.F.. 2.
Through intestinal absorption, bone resorption, and renal resorption, Vitamin D helps to modulate the skeletal and mineral homeostasis.
Vitamin D has shown to express transient downregulation of OPG, thus causing bone resorption. However, long-term usage of vitamin D causes the recovery of OPG expression. In this form, Vitamin D causes the inhibition of B-cell-mediated antibody production, cytokine production, and T-cell proliferation. It also causes the inhibition of the maturation and differentiation of dendritic cells, thereby maintaining the immature, tolerogenic phenotype by downregulating the expression of Major Histocompatibility Complex Class II molecules, thus lowering its immune stimulating ability.
Deficiency of Vitamin D Due to the limitation of the dietary sources of Vitamin D and inconsistent or inadequate uptake of food, the main source of Vitamin D is sunlight. However, the amount of UVB rays from sunlight and its effectiveness is influenced by various factors, which include time, season, latitude, altitude, clothing, sunscreen use, pigmentation, and age.
This makes Vitamin D deficiency a more common problem than previously thought. Recent studies reported that Vitamin D deficiency may play an evident role in periodontal disease and loss of teeth among nonpregnant adults. Vitamin D also plays an important role in bone formation and preservation,  and recently, it was observed that alveolar bone loss due to periodontal disease is more pronounced in osteoporotic bone.
Treatment Strategy The traditional and most cost-effective way of obtaining Vitamin D is through sunlight. A 5—10 min of mid-day, mid-year exposure of arms and legs of a light-colored Caucasian individual can produce up to IU of Vitamin D3 in the epidermis of human skin, which can increase up to 10, IU in case of a whole body exposure.
Therefore, there arises a need for Vitamin D supplementation. However, D3 is considered more effective than D2 primarily to differences in serum half-life as D3 has a longer half-life; thus, it reduces the frequency of the doses required.
The US government recommends IU daily Vitamin D intake for individuals of more than 50 years, IU for individuals between 50 and 7-years, and IU for individuals more than 70 years of age. However, the major limitation of this investigation was that the study included the supplementation of calcium along with Vitamin D; therefore, the effects of Vitamin D alone could not be studied. Moreover, tooth loss was a secondary outcome in the study, and tooth counts were based on self-reports by participants who completed the study.
However, this study also included the supplementation of calcium along with Vitamin D. In addition, no radiographic analysis was done and little information was provided regarding the assessment of periodontal health in this study. Introduction Chronic periodontitis is an inflammatory disease caused by dentogingival bacterial plaques and if left untreated, it causes progressive destruction of periodontal tissues, ultimately leading to tooth loss.
In a subset of subjects with chronic periodontitis, there may be an increased risk of cardiovascular disease, diabetes mellitus, and complications of pregnancy [ 1 — 4 ]. Vitamin D plays a role in maintaining the homeostasis of various biological systems including the neuromuscular, skeletal, cutaneous, cardiovascular, and immune systems.
In addition, vitamin D has tumour suppressing, anti-inflammatory, and antibacterial properties [ 8 — 12 ] Figure 1.
International Journal of Dentistry
While there is no doubt about the essential role of vitamin D in maintaining bone and calcium homeostasis, its role in other biological systems is less well-defined [ 13 ].
The functions of vitamin D. Cross-sectional observational studies show that vitamin D deficiency may be associated with increased risk of chronic periodontitis [ 1614 — 17 ], and that supplementation with vitamin D alone, or with vitamin D together with calcium may help to maintain periodontal health, may increase mineral density of the jaws, and may inhibit inflammatory alveolar bone resorption [ 1518 — 21 ].
Furthermore, in subjects with adequate vitamin D, surgical treatment for chronic periodontitis appears to be more successful than in subjects with vitamin D deficiency [ 22 ]. However, results of some longitudinal studies show that vitamin D deficiency is a poor predictor of progressive tissue destruction in subjects with chronic periodontitis [ 7 ] and conversely, vitamin D sufficiency does not protect against progression of chronic periodontitis [ 23 ].
These longitudinal studies do not provide any information regarding the association between vitamin D levels and chronic periodontitis in the general population. Cross-sectional observational studies also show that vitamin D deficiency, independently of chronic periodontitis, is associated with increased risk of cardiovascular disease [ 91024 ], but it is not known if concurrence of periodontal disease and vitamin D deficiency poses a cumulative cardiovascular risk.
In any case, there are no strong evidence-based data to show that supplementation with vitamin D reduces the incidence or the severity of cardiovascular or of any immunoinflammatory diseases [ 92425 ]. Nevertheless, vitamin D has been used in prevention or treatment of a number of infections including respiratory infections [ 26 ], gingivitis [ 27 ], and influenza [ 28 ] and in the management of asthma [ 29 ].
Owing to climatic variations and variations in skin pigmentation, according to generally accepted norms of serum levels of vitamin D, deficiency of vitamin D is very common. Standard treatment of periodontal disease focuses on reducing the dentogingival bacterial load through personal and professional mechanical disruption of the biofilm, by the use of local or systemic antibacterial agents, or by downregulating the immunoinflammatory response with drugs in order to reduce the bacteria-induced inflammation and to arrest the progression of periodontal tissue damage [ 31 ].
If indeed vitamin D were to be found to be effective in the prevention and treatment of periodontitis, then it should be added to the arsenal of biologically active therapeutic agents.
In this narrative review, we describe the possible mechanisms by which vitamin D deficiency may play roles in the pathogenesis of chronic periodontitis and in maintaining the homeostasis of the oral epithelium and the integrity of oral immunity.
In a modern diet, food supplements substantially augment the natural sources. The term vitamin D refers either to vitamin D2 or to vitamin D3 or to both, and either can be used for correcting vitamin D deficiency [ 2532 ]. Exposure to sunlight is essential for achieving a sufficient level of vitamin D [ 252933 ], but as the available evidence suggests that excessive exposure to sunlight raises the risk of skin cancer, it is common practice to avoid exposure to sunlight or to wear protective clothing and to use sunscreen with high protection factors when outdoors [ 3435 ].
Under these circumstances, it is difficult without supplementation to attain sufficient levels of vitamin D for vitamin D-related physiological activities [ 25 ]. Because melanin reduces the penetration of UVB into the skin, diminishing the photoproduction of vitamin D, black people are more frequently vitamin D deficient than white people [ 530 ].
This may contribute minimally to the greater severity of chronic periodontitis in blacks than in whites [ 5 ]. Both vitamin D2 and D3 are biologically inactive and are converted in the liver into 25 OH D which then is converted mainly by the proximal tubular cells of the renal nephrons into 1,25 OH 2D.
This is the biologically active vitamin D Figure 2. However, other tissues can also to a lesser extent convert vitamin D2 and D3 to the biologically active form [ 13253236 ]. Synthesis of vitamin D precursors and metabolites. As the 1,25 OH 2D has a half-life of only about 4 hours, 25 OH D with a half-life of weeks is used to determine serum levels of vitamin D.
Metabolites of vitamin D are transported in the circulation by the vitamin D binding protein, and upon reaching their target cells, they dissociate from the binding protein and enter the cells [ 81925323738 ]. The biochemical properties of vitamin binding protein which is the principle transporter of vitamin D and its metabolites, determine the free levels of free vitamin D available to the tissues [ 33 ]. Regulation of the concentration of circulating 25 OH D and 1,25 OH 2D is a complex process which is modulated by multiple factors including age, sunlight exposure duration and intensitydiet oily fish such as tuna, salmon, sardines; cod liver oil; yeast and fungiplasma calcium, parathyroid hormone, direct feedback by 1,25 OH 2D, fibroblast growth factor 23, diseases i.
As older adults are often less exposed to sunlight and have reduced capacity to produce biologically active vitamin D metabolites and to absorb vitamin D from the intestine and may be suffering from chronic diseases requiring multiple-drug treatment, they are at particular risk of vitamin D deficiency [ 12 ].
For the best clinical outcomes of vitamin D supplementation, daily doses are better than higher weekly or monthly doses [ 12 ] because daily doses result in a more stable serum and tissue concentration [ 38 ].
However, VDR may mediate cellular functions in a ligand-independent manner [ 13 ].
VDR polymorphism has been associated with increased risk of several diseases, with some of the genetic variants being less responsive than others to 1,25 OH 2D in suppressing inflammatory processes, thus favouring the development of cutaneous inflammatory conditions [ 41 ] and possibly of chronic periodontitis [ 542 ].
Vitamin D deficiency has the potential to interfere with bone homeostasis, but as long as calcium serum levels are normal, bone metabolism appears not to be affected by vitamin D deficiency [ 13 ].
Oral Mucosal Immunity The oral mucosal epithelium separates a microorganism-ridden environment from the underlying connective tissue. It acts as the physical barrier that protects the deeper tissues from penetration of water and a wide range of water-soluble molecules, from invasion by microorganisms with their associated antigens and toxins, and from minor mechanical damage [ 43 ].
The epithelium and the underlying lamina propria of the oral mucosa are populated by innate immune cells including macrophages, natural killer NK cells, NKT cells, polymorphonuclear leukocytes, and dedicated antigen-presenting cells, with all their related cytokines and chemokines [ 43 ].
Salivary flow, salivary secretory immunoglobulin A, and gingival crevicular fluid are additional physical and biological elements of oral mucosal immunity [ 43 ].
Oral mucosal immunity has many functions including control of colonization of the oral mucosa by pathogenic microorganisms, generation of protective immunoinflammatory responses against invading pathogens, mediation of immune tolerance to commensal microorganisms and foreign antigens derived from exogenous sources, and neutralization of harmful exogenous antigens [ 47 ].
Oral keratinocytes and innate immune cells in the lamina propria of the oral mucosa express molecular pattern-recognition receptors that can detect microorganisms and harmful endogenous molecules derived from tissue damage.
Vitamin D Deficiency as It Relates to Oral Immunity and Chronic Periodontitis
There are several families of molecular pattern-recognition receptors including the Toll-like receptor TLR family, the c-type lectin receptor family, and the mannose receptor family [ 4647 ]. Stimulation of TLR receptors by periodontopathic bacteria breaching the crevicular epithelium triggers the production of antibacterial and chemotactic agents, inflammatory mediators, and cytokines.
All of these induce a nonspecific inflammatory reaction and mobilize dedicated antigen-presenting cells to the infected gingival site. In turn, these biological reactions initiate and drive adaptive immunoinflammatory reactions [ 434647 ].
Invasion of the gingival epithelium by periodontopathic bacteria brings about activation of keratinocytes, myeloid dendritic cells, and macrophages. After having recognized molecular patterns of periodontopathic bacteria through TLRs, local immature myeloid dendritic cells process the pathogenic antigen and undergo maturation, with upregulation of expression of major histocompatibility complex MHC and costimulatory surface molecules.
The subtype and the magnitude of the antigen-specific T cell response in the lymph nodes is determined by the nature of the infective agent, by the cytokine profile in the microenvironment, by the specific T cell receptor repertoire, and by the profile of the cell surface molecules expressed by antigen-presenting dendritic cells [ 4347 ].
Some of the effector T cells will remain in the lymph nodes, others will enter the circulation, and those which reach the oral mucosa will engage in local effector immune responses and in immune surveillance [ 43 ]. In addition, Treg cells via IL downregulate the induction of T-cell-mediated immune responses in the lymph nodes and suppress the activity of T-cells in the peripheral tissue, thus mediating immune tolerance and preventing upregulation of immunoinflammatory reactions [ 4347 ].
Despite this process of T cell polarization, the polarized T cells retain some functional versatility, having the capacity to produce cytokines which are not considered lineage-specific [ 43 ].