Vitamin D: Unveiling the Crucial Trifecta – Teeth, Immune System, and Bones

Abstract

According to recent studies, vitamin D insufficiency is connected with the occurrence of various diseases, including cancer, cardiovascular disease, and neurological disorders. Understanding the elements that regulate vitamin D intake and enhancement is crucial to preserving health and preventing the beginning of disease. With this review, we seek to shed light on the relevance of vitamin D for the human skeletal and immunological systems, as well as for the teeth and periodontium. Vitamin D is a collective word for cholecalciferol (vitamin D3, the active form of vitamin D) and ergocalciferol (vitamin D2, the inactive form of vitamin D), both of which are precursors of hormones that play significant roles in calcium and phosphate metabolism and skeletal homeostasis. Since the usual human diet lacks both vitamin D2 (of plant origin) and vitamin D3 (of animal origin), people rely on their own generation of vitamin D3 in UVB-irradiated skin.^1,2

Vitamin D and the immune system

Vitamin D is a key nutrient that plays a significant role in regulating the function of the immune system. Vitamin D has been found to change the way immune cells respond to diverse stimuli and can regulate the production of cytokines, signalling molecules essential for mediating immunological responses. In addition, vitamin D can also influence the function of T cells, B cells and macrophages, all of which are key components of the immune system (Fig. 1).³

Fig. 1

In summary, vitamin D plays a critical role in regulating the function of the immune system and has an immunomodulatory effect. Maintaining adequate vitamin D levels is necessary for good immune system function and may help lower the risk of autoimmune disorders and respiratory infections.^4,5

Vitamin D and Bones

The role of vitamin D is crucial in preventing osteoporosis, a medical condition that weakens bones and makes them more susceptible to fractures. Individuals with low levels of vitamin D are at a higher risk of developing osteoporosis and other bone-related conditions.¹

Vitamin D affects calcium and bone metabolism in a variety of ways. One of its most important roles is controlling how well calcium (Ca) is absorbed in the gut. This is essential for optimum bone mineralization throughout growth, for adult bone protection, and for osteoporosis prevention.

A hormone that promotes gene transcription after connecting to the intestinal vitamin D receptor is known as ^1,25(OH)2 D and it controls intestinal calcium absorption; thus, the endocrine system, which regulates the optimal level of calcium throughout the body, is also highly dependent on vitamin D and its metabolites.
This hormonal control aims to maintain serum calcium levels within a relatively small range by regulating them. To accomplish this, regulatory actions take place in many tissues, including the parathyroid gland, kidney, bone, and intestines (Fig.2).⁶

Fig. 2

Studies have shown when genes that regulate vitamin D function, such as the vitamin D receptor gene, are eliminated or deleted, mice cannot adapt to a low-calcium diet. The amount of calcium absorbed in the gut is controlled by vitamin D, which has a significant impact on the body. The study on mice found that the body needs more calcium when a mouse is pregnant, aging, or going through menopause; at these times vitamin D helps increase calcium absorption from food. However, mice are unable to absorb enough calcium from low-calcium diets if they lack the genes that control vitamin D activity.⁷

The phrase “palate” or “human growth palate” refers to the roof of the mouth. It is important for numerous tasks, such as breathing, speaking, and swallowing. To fully appreciate how vitamin D affects the growth of the human palate and how our bodies absorb it in the gut, more research is required. In order to prevent osteoporosis and lessen the risk of fractures in middle-aged and older adults, calcium and vitamin D supplements are utilized. Vitamin D levels vary widely throughout persons. It is vital to take into account a range of factors that affect vitamin D production and metabolism when doing longitudinal investigations. Studies on vitamin D demonstrate that it is extremely dependent on its receptor and how vitamin D is bound. The interaction between receptor and vitamin D could be responsible for the further steps of vitamin D action.⁸

Vitamin D and Oral Health

Improving oral health requires an understanding of the complex effects that vitamin D has on the mouth. By examining how vitamin D affects the oral cavity, periodontal disease, antimicrobial activity, precancerous lesions, and orthodontics, we might learn more about potential preventive and therapeutic strategies. For oral health and general health, studies have demonstrated that adequate vitamin D levels must be maintained (Fig. 4).

Fig. 4

Mineralization and demineralization balance

Vitamin D has an impact on oral health that goes beyond bone metabolism. Lack of vitamin D can hinder the growth of teeth and result in weak, undermineralized teeth that are more prone to fractures and decay. Tooth hypomineralization is a disorder that leads to weak and brittle teeth because tooth enamel does not grow adequately. Dentists can aid in improving tooth mineralization and lowering the risk of dental issues by addressing vitamin D deficiency.⁹ Al-Jubori et al. (2022) came to the conclusion in their study that oral vitamin D intake can encourage adsorption and subsequently, remineralization of early lesions on the enamel surface, improving surface microhardness and mineral content (calcium and phosphorus weight percentage) of demineralized tooth surfaces, allowing them to remineralize and become more resistant to decay.¹⁰

Periodontal health

Vitamin D deficiency has also been associated with poorer periodontal health and may contribute to the immune system’s decreased defence against periodontal infections. Recent studies have found a connection between vitamin D deficiency and periodontitis. Additionally, this insufficiency has also been linked to several systematic diseases, such as rheumatic, cardiovascular, female-related conditions, and diabetes mellitus.¹¹ In general, the host immune system initiates the inflammatory and immunological responses to periodontal infections. As was previously mentioned, periodontitis patients with low salivary vitamin D levels had higher levels of inflammatory biomarkers (specifically, IL-35, IL-17A) than periodontally healthy patients. Low levels of vitamin D in saliva suggest the existence of an inflammatory microenvironment. Surprisingly, vitamin D intake before nonsurgical periodontal treatment was associated with a decrease in cytokines in saliva. By reducing cytokines (proteins involved in inflammation) in saliva, we can reduce the inflammation that directly affects the periodontium.¹²

Studies have shown an association between vitamin D levels in serum and chronic periodontitis. Patients diagnosed with chronic periodontitis had lower serum levels of vitamin D than periodontally healthy patients, potentially indicating that vitamin D is important for maintaining a healthy periodontium. These findings are clinically relevant considering that vitamin D plays an important role in bone maintenance and the immune system.¹¹

Antimicrobial effect of vitamin D via antimicrobial peptides

Ultraviolet-B radiation most likely reduces the risk of dental caries by stimulating the production of vitamin D and, in turn, antimicrobial peptides, which have antibacterial properties. These peptides can ward off various harmful microorganisms such as bacteria, viruses and fungi and act like our body’s natural antibiotics.

Antimicrobial peptides not only kill these harmful invaders but also help to strengthen the natural defences of our immune system. Vitamin D plays a key role in this process by activating the genes that produce these peptides. One important peptide called Cathelicidin can directly destroy pathogens or activate other immune cells to fight infections.^13–15

In our mouths, our salivary glands and oral mucosa produce these antimicrobial peptides, protecting us from a variety of harmful microorganisms. This suggests that antimicrobial peptides could be used to control the growth of microbes in the mouth and prevent the formation of plaque.¹⁶

Prevention of oral precancerous lesions

There is still much to learn about how vitamin D affects the onset and progression of specific oral malignancies. Vitamin D deficiency occurs more frequently in patients with oral malignant tumours. Squamous cell cancer of the esophagus, mouth, and pharynx, which is more frequent among heavy smokers and heavy drinkers, was linked in case-controlled study to vitamin D deficiency.^9,17 Recent preclinical research strongly supports the usefulness of vitamin D in cancer prevention by exerting a wide range of cellular activities on cancer cells.¹⁸

Studies have indicated that vitamin D induces programmed cell death; it has pro-apoptotic (programmed cell death) properties in precancerous oral lesions. Apoptosis of infected cells is part of the host defence mechanism. Vitamin D can also prevent the growth of new blood vessels, which limits the blood supply to the lesion. Additionally, vitamin D has anti-inflammatory properties, which means that it can reduce inflammation linked to precancerous lesions.

The growth and division of cells in these oral lesions are also substantially slowed by vitamin D’s antiproliferative impact. By limiting the invasive behaviour of cells and preventing the spread of these cells to surrounding tissues, it also has an anti-invasive effect. Last but not least, vitamin D has demonstrated anti-metastatic activity by successfully blocking the spread of cancer cells from precancerous oral lesions to far-off areas of the body. Overall, the multiple effects of vitamin D contribute to its potential role in the prevention and treatment of precancerous oral lesions and underscore its therapeutic importance for oral health (Fig.3).¹⁹

Fig. 3

Orthodontics

The action of predefined orthodontic forces causes mechanical stimuli that result in two simultaneous processes that move the teeth: bone resorption at the pressure site by osteoclastic activity and bone creation at the stress site by osteoblastic activity. These two procedures may cause teeth to move more quickly when coupled with mechanical, chemical, or electrical stimuli. Regarding chemical components, vitamin D has shown encouraging outcomes and may be crucial in tooth movement during orthodontic therapy.²⁰

Conclusion

It is important for dental patients to be analysed by dentists and have their vitamin D levels tested before undergoing major dental procedures, such as implants, to ensure safety and optimal results. Adequate vitamin D levels are very important for healthy bone formation and healing, which are critical to the success of dental implants. By determining vitamin D levels, clinicians can identify any deficiencies or insufficiencies and take appropriate action to optimize bone health and promote better healing, ultimately increasing patient safety and treatment effectiveness.

To summarize, vitamin D has a substantial impact on the health of teeth, bones, and the immune system. Vitamin D has been shown in studies to be beneficial in preserving healthy teeth and bones as well as improving immune system performance (Fig.4). Despite this, there is still a need for more scientific research to completely understand the extent and methods by which vitamin D promotes various aspects of health. Nonetheless, it is obvious that vitamin D has favourable benefits, and ensuring enough intake is critical for excellent oral health, bone strength, and a strong immune system.

Oral Health welcomes this original article.

References

1. Khazai N, Judd SE, Tangpricha V. Calcium and vitamin D: Skeletal and extraskeletal health. Curr Rheumatol Rep. 2008 Apr 4;10(2):110–7.
2. Holick MF. Vitamin D Deficiency. https://doi.org/101056/NEJMra070553 [Internet]. 2007 Jul 19 [cited 2023 Mar 15];357(3):266–81. Available from: https://www.nejm.org/doi/full/10.1056/nejmra070553
3. Aranow C. Vitamin D and the Immune System. https://doi.org/102310/JIM0b013e31821b8755 [Internet]. 2011 Aug 1 [cited 2023 Mar 15];59(6):881–6. Available from: https://journals.sagepub.com/doi/abs/10.2310/JIM.0b013e31821b8755?journalCode=imja
4. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients [Internet]. 2013 Jul 5 [cited 2023 Mar 20];5(7):2502–21. Available from: https://pubmed.ncbi.nlm.nih.gov/23857223/
5. Ao T, Kikuta J, Ishii M. The effects of vitamin D on immune system and inflammatory diseases. Biomolecules. 2021 Nov 1;11(11).
6. Fleet JC. The role of vitamin D in the endocrinology controlling calcium homeostasis. Mol Cell Endocrinol. 2017 Sep;453:36–45.
7. Fleet JC. Vitamin D-Mediated Regulation of Intestinal Calcium Absorption. Nutrients. 2022 Aug 16;14(16):3351.
8. Muresan GC, Hedesiu M, Lucaciu O, Boca S, Petrescu N. Effect of Vitamin D on Bone Regeneration: A Review. Medicina (Kaunas) [Internet]. 2022 Oct 1 [cited 2023 Mar 20];58(10). Available from: https://pubmed.ncbi.nlm.nih.gov/36295498/
9. Botelho J, Machado V, Proença L, Delgado AS, Mendes JJ. Vitamin D Deficiency and Oral Health: A Comprehensive Review. Nutrients. 2020 May 19;12(5):1471.
10. Al-Jubori SH, AL-Murad MA, Al-Mashhadane FA. Effect of Oral Vitamin D3 on Dental Caries: An In-Vivo and In-Vitro Study. Cureus. 2022 May 26;
11. Machado V, Lobo S, Proença L, Mendes JJ, Botelho J. Vitamin D and Periodontitis: A Systematic Review and Meta-Analysis. Nutrients. 2020 Jul 22;12(8):2177.
12. Jagelavičienė E, Vaitkevičienė I, Šilingaitė D, Šinkūnaitė E, Daugėlaitė G. The Relationship between Vitamin D and Periodontal Pathology. Medicina (B Aires). 2018 Jun 12;54(3):45.
13. Roider E, Ruzicka T, Schauber J. Vitamin D, the Cutaneous Barrier, Antimicrobial Peptides and Allergies: Is There a Link? Allergy Asthma Immunol Res. 2013;5(3):119.
14. Grant WB. How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer? An examination using Hill’s criteria for causality. Dermatoendocrinol. 2009 Jan 29;1(1):17–24.
15. Bartley J. Vitamin D: emerging roles in infection and immunity. Expert Rev Anti Infect Ther. 2010 Dec 10;8(12):1359–69.
16. Khurshid Z, Naseem M, Sheikh Z, Najeeb S, Shahab S, Zafar MS. Oral antimicrobial peptides: Types and role in the oral cavity. Saudi Pharmaceutical Journal. 2016 Sep;24(5):515–24.
17. Fathi N, Ahmadian E, Shahi S, Roshangar L, Khan H, Kouhsoltani M, et al. Role of vitamin D and vitamin D receptor (VDR) in oral cancer. Biomedicine & Pharmacotherapy. 2019 Jan;109:391–401.
18. Hung M, Almpani K, Thao B, Sudweeks K, Lipsky MS. Vitamin D in the Prevention and Treatment of Oral Cancer: A Scoping Review. Nutrients. 2023 May 17;15(10):2346.
19. Feldman D, Krishnan A V., Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014 May 4;14(5):342–57.
20. Khalaf RM, Almudhi AA. Effects of vitamin D deficiency on the rate of orthodontic tooth movement: An animal study. Saudi Dent J. 2022 Feb;34(2):129–35.

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About the Authors

Dr. Dora Dragičević is a PhD student in Molecular Biosciences in Osijek. She graduated from the Faculty of Medicine in Split, Croatia, in Dentistry. She worked as a polyvalent dentist for three years and since 2020 she has been a teaching assistant at the Faculty of Dental Medicine and Health Josip Juraj Strossmayer, Osijek.

Dr. Željka Perič Kaćarević, associate professor Berlin, Germany. She graduated in molecular biology in Osijek. She has been employed as Associate Professor by the Department of Anatomy/ Histology, Embryology, and Pathology, Faculty of Dental Medicine and Health, University of Osijek. In the same year she started in scientific research with the regenerative biomedical materials at Botiss biomaterials GmbH, Berlin, Germany.

Dr. Svenja Rogge, DDS, PhD Botiss biomaterials AG, Berlin, Germany. She studied Dental Medicine at the Albert Ludwigs University, Freiburg, Germany and graduated in 1999. She initially worked in a private dental office and from 2001 at Charité Berlin. In 2003 she obtained her PhD in Dentistry. Since 2017 Dr. Rogge has been the head of New Developments & Techniques at Botiss and has been responsible for the development of new innovative product lines.