Beyond the bones: the genomic and clinical landscape of vitamin D deficiency

Authors

  • Ahmed S. Naqvi Bahrain Defence Forces Hospital, Part - Time Clinical Senior Lecturer in Medicine with Royal College of Surgeons of Ireland, Bahrain
  • Sadaf Saeed Continuing Dental and Medical Education (CODE-M), Karachi, Pakistan
  • Muznah Subzwari Cancer Foundation Hospital, Karachi, Pakistan
  • Abdul B. Naqvi Jinnah Postgraduate Medical Centre, Karachi, Pakistan

DOI:

https://doi.org/10.18203/2394-6040.ijcmph20254079

Keywords:

Vitamin D, Immune modulation, Neuroprotection, Endocrine and metabolic regulation, Systemic health

Abstract

Vitamin D, a secosteroid hormone traditionally linked with bone health, has emerged as a pleiotropic regulator exerting systemic effects across immune, neurological, endocrine, respiratory, and metabolic pathways. This review explores the expanding scientific consensus on vitamin D's roles beyond musculoskeletal physiology, emphasizing its contributions to innate immunity, antimicrobial defense, tumor suppression, neurocognitive regulation, reproductive health, and gene expression via epigenetic pathways. Current evidence suggests that vitamin D modulates inflammation, improves insulin sensitivity, supports mucosal defense, and regulates transcription of multiple health-relevant genes. In diseases such as polycystic ovary syndrome (PCOS), periodontal disorders, multiple sclerosis, and metabolic syndrome, vitamin D deficiency is consistently linked with disease progression and poor clinical outcomes. Furthermore, its deficiency is associated with impaired quality of life, fatigue, reduced neuromuscular function, and increased infection susceptibility. Despite the variation in individual responsiveness and ongoing debates regarding universal supplementation, targeted screening and correction of deficiency in high-risk populations appear justified. This synthesis underscores the necessity for precision nutrition, personalized supplementation strategies, and integrative clinical guidelines to harness vitamin D’s full systemic potential.

Metrics

Metrics Loading ...

Author Biographies

Muznah Subzwari, Cancer Foundation Hospital, Karachi, Pakistan

Resident Medical Officer at Cancer Foundation Hospital, Karachi

Abdul B. Naqvi, Jinnah Postgraduate Medical Centre, Karachi, Pakistan

House Officer at Jinnah Postgraduate Medical Centre, Karachi, Pakistan

References

Sirbe C, Rednic S, Grama A, Pop TL. An update on the effects of vitamin D on the immune system and autoimmune diseases. Int J Mol Sci. 2022;23(17):9784. DOI: https://doi.org/10.3390/ijms23179784

Zmijewski MA. Nongenomic activities of vitamin D. Nutrients. 2022;14(23):5104. DOI: https://doi.org/10.3390/nu14235104

Zhang S, Miller DD, Li W. Non-musculoskeletal benefits of vitamin D beyond the musculoskeletal system. Int J Mol Sci. 2021;22(4):2128. DOI: https://doi.org/10.3390/ijms22042128

Wimalawansa SJ. Infections and autoimmunity—the immune system and vitamin D: a systematic review. Nutrients. 2023;15(17):3842. DOI: https://doi.org/10.3390/nu15173842

Alam S, Ahmad J, Osama M, Khan AR. Overview of the vital role of vitamin D: functions, deficiency syndromes, and impact throughout life. Curr Pharm Rep. 2025;163-7. DOI: https://doi.org/10.63785/cpr.2025.1.1.125136

Siddiqee MH, Bhattacharjee B, Siddiqi UR, Meshbahur Rahman M. High prevalence of vitamin D deficiency among South Asian adults: a systematic review and meta-analysis. BMC Public Health. 2021;21(1):1823. DOI: https://doi.org/10.1186/s12889-021-11888-1

Mohan A, Haider R, Fakhor H, Hina F, Kumar V, Jawed A, et al. Vitamin D and polycystic ovary syndrome (PCOS): a review. Ann Med Surg (Lond). 2023;85(7):3506-11. DOI: https://doi.org/10.1097/MS9.0000000000000879

Gallo D, Baci D, Kustrimovic N, Lanzo N, Patera B, Tanda ML, et al. How does vitamin D affect immune cells crosstalk in autoimmune diseases? Int J Mol Sci. 2023;24(5):4689. DOI: https://doi.org/10.3390/ijms24054689

Argano C, Torres A, Orlando V, Cangialosi V, Maggio D, Pollicino C, et al. Molecular insight into the role of vitamin D in immune-mediated inflammatory diseases. Int J Mol Sci. 2025;26(10):4798. DOI: https://doi.org/10.3390/ijms26104798

Cui X, Eyles DW. Vitamin D and the central nervous system: causative and preventative mechanisms in brain disorders. Nutrients. 2022;14(20):4353. DOI: https://doi.org/10.3390/nu14204353

Mirarchi A, Albi E, Beccari T, Arcuri C. Microglia and brain disorders: the role of vitamin D and its receptor. Int J Mol Sci. 2023;24(15):11892. DOI: https://doi.org/10.3390/ijms241511892

Macova L, Kancheva R, Bicikova M. Molecular regulation of the CNS by vitamin D. Physiol Res. 2023;72. DOI: https://doi.org/10.33549/physiolres.935248

Lason W, Jantas D, Leskiewicz M, Regulska M, Basta-Kaim A. The vitamin D receptor as a potential target for the treatment of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases: a narrative review. Cells. 2023;12(4):660. DOI: https://doi.org/10.3390/cells12040660

Anwar MJ, Alenezi SK, Alhowail AH. Molecular insights into the pathogenic impact of vitamin D deficiency in neurological disorders. Biomed Pharmacother. 2023;162:114718. DOI: https://doi.org/10.1016/j.biopha.2023.114718

Wassif GA, Alrehely MS, Alharbi DM, Aljohani AA, Wassif G. The impact of vitamin D on neuropsychiatric disorders. Cureus. 2023;15(10). DOI: https://doi.org/10.7759/cureus.47716

Vyas CM, Mischoulon D, Chang G, Reynolds CF 3rd, Cook NR, Weinberg A, et al. Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention. J Psychiatr Res. 2023;163:357-64. DOI: https://doi.org/10.1016/j.jpsychires.2023.05.069

Jensen LT, Fugger L. Immune perturbation by the ileal microbiota in multiple sclerosis. Proc Natl Acad Sci U S A. 2025;122(21). DOI: https://doi.org/10.1073/pnas.2506777122

Bingol FG, Kocyigit E, Celik E, Agagunduz D, Budan F. Breaking the cycle: can vitamin D bridge the gap between gut microbiota and immune dynamics in multiple sclerosis? Int J Mol Sci. 2025;26(12):5464. DOI: https://doi.org/10.3390/ijms26125464

Gulisija J, Capkun V, Golic S, Stipic SS. Vitamin D serum levels and the development of intensive care unit-acquired weakness: insights from a COVID-19 intensive care cohort. Pathophysiology. 2025;32(2):21. DOI: https://doi.org/10.3390/pathophysiology32020021

Li M, Yang Y, Chen T, Luo Y, Zhang Y, Liu H, et al. FTO deficiency aggravates age-dependent depression-like behaviors and cognitive impairment. Behav Brain Funct. 2025;21(1). DOI: https://doi.org/10.1186/s12993-025-00280-3

Lopez-Gil JF, Cisneros-Vasquez E, Olivares-Arancibia J, Yanez-Sepulveda R, Gutierrez-Espinoza H. Investigating the relationship between ultra-processed food consumption and academic performance in the adolescent population: the EHDLA study. Nutrients. 2025;17(3):524. DOI: https://doi.org/10.3390/nu17030524

Bandaru N, Bonthu MG, Gayatri AP, Metri S, Kumar PK, Addanki A, et al. Exploring role of vitamin D on Alzheimer’s disease: mechanistic insights and implications. J Pharmacol Pharmacother. 2025;16(2):164-71. DOI: https://doi.org/10.1177/0976500X241312726

Zhang R, Zhang M, Wang P. The intricate interplay between dietary habits and cognitive function: insights from the gut-brain axis. Front Nutr. 2025;12:1539355. DOI: https://doi.org/10.3389/fnut.2025.1539355

Ghaseminejad-Raeini A, Ghaderi A, Sharafi A, Nematollahi-Sani B, Moossavi M, Derakhshani A, et al. Immunomodulatory actions of vitamin D in various immune-related disorders: a comprehensive review. Front Immunol. 2023;14:950465. DOI: https://doi.org/10.3389/fimmu.2023.950465

Gou Z, Li F, Qiao F, Maimaititusvn G, Liu F. Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study. Front Nutr. 2023;10:1162442. DOI: https://doi.org/10.3389/fnut.2023.1162442

Galindo-Mendez M, Galindo-Ruiz M, Concheso-Venegas MF, Mendoza-Molina SU, Orozco-Cruz D, Weintraub-Benzion E. The impact of vitamin D in the prevention of influenza, COVID-19, and dengue: a review. Biomedicines. 2025;13(4):927. DOI: https://doi.org/10.3390/biomedicines13040927

Grunbaum A. Relationship between vitamin D status and COVID-19 severity: does vitamin D help protect against severe COVID-19 illness? McGill University (Canada). 2023.

Qin L. Immune function (serum IL-4 and IL-5), nutritional status, and clinical outcomes in children with bronchial asthma after vitamin D supplementation. J Med Biochem. 2025;44(5):1059-66. DOI: https://doi.org/10.5937/jomb0-56915

Jolliffe D, Brustad N, Chawes B, Cooper C, D’Angelo S, Harvey N, et al. Maternal vitamin D supplementation during pregnancy to prevent acute respiratory infections in offspring: systematic review and meta-analysis. SSRN. 2025. DOI: https://doi.org/10.2139/ssrn.5246534

Simon P, Torok E, Szalontai K, Kari B, Neuperger P, Zavala N, et al. Nutritional support of chronic obstructive pulmonary disease. Nutrients. 2025;17(7):1149. DOI: https://doi.org/10.3390/nu17071149

Asghari S, Hamedi-Shahraki S, Amirkhizi F. Vitamin D status and systemic redox biomarkers in adults with obesity. Clin Nutr ESPEN. 2021;45:292-8. DOI: https://doi.org/10.1016/j.clnesp.2021.07.032

Han L, Xu XJ, Zhang JS, Liu HM. Association between vitamin D deficiency and levels of renin and angiotensin in essential hypertension. Int J Clin Pract. 2022;2022:8975396. DOI: https://doi.org/10.1155/2022/8975396

Alnimer A, Bhamidimarri PM, Talaat IM, Alkhayaal N, Eltayeb A, Ali N, et al. Association between expression of vitamin D receptor and insulin-like growth factor 1 receptor among breast cancer patients. World J Oncol. 2023;14(1):67. DOI: https://doi.org/10.14740/wjon1550

Chu C, Tsuprykov O, Chen X, Elitok S, Kramer BK, Hocher B. Relationship between vitamin D and hormones important for human fertility in reproductive-aged women. Front Endocrinol (Lausanne). 2021;12:666687. DOI: https://doi.org/10.3389/fendo.2021.666687

Cui A, Zhang T, Xiao P, Fan Z, Wang H, Zhuang Y. Global and regional prevalence of vitamin D deficiency from 2000 to 2022: pooled analysis of 7.9 million participants. Front Nutr. 2023;10:1070808. DOI: https://doi.org/10.3389/fnut.2023.1070808

Arora J, Patel DR, Nicol MJ, Field CJ, Restori KH, Wang J, et al. Vitamin D and the ability to produce 1,25(OH)2D are critical for protection from viral infection of the lungs. Nutrients. 2022;14(15):3061. DOI: https://doi.org/10.3390/nu14153061

Sabico S, Wani K, Grant WB, Al-Daghri NM. Improved HDL cholesterol through vitamin D correction reduces 10-year ASCVD risk in vitamin D-deficient adults. Nutrients. 2023;15(3):551. DOI: https://doi.org/10.3390/nu15030551

Han YY, Hsu SHJ, Su TC. Association between vitamin D deficiency and high serum levels of small dense LDL in middle-aged adults. Biomedicines. 2021;9(5):464. DOI: https://doi.org/10.3390/biomedicines9050464

Tsoukalas D, Sarandi E, Fragoulakis V, Xenidis S, Mhliopoulou M, Charta M, et al. Metabolomics-based treatment for chronic diseases: results from a multidisciplinary clinical study. BMJ Nutr Prev Health. 2024;7(2):357-65. DOI: https://doi.org/10.1136/bmjnph-2024-000883

Nwosu BU, Pappachan JM, Ashraf AP. Editorial: disease-modifying approaches in type 1 diabetes. Front Endocrinol. 2025;16. DOI: https://doi.org/10.3389/fendo.2025.1624146

Ahmad R, Sarraj B, Razzaque MS. Editorial: vitamin D and mineral ion homeostasis: endocrine dysregulation in chronic diseases. Front Endocrinol. 2025;16. DOI: https://doi.org/10.3389/fendo.2025.1493986

Abboud M. Vitamin D supplementation and sleep: a systematic review and meta-analysis. Nutrients. 2022;14(5):1076. DOI: https://doi.org/10.3390/nu14051076

Vassalle C. Editorial: vitamin D—from pathophysiology to clinical impact. Front Nutr. 2025;12. DOI: https://doi.org/10.3389/fnut.2025.1572567

Engin MMN, Ozdemir O. Role of vitamin D in COVID-19 and other viral infections. World J Virol. 2024;13(3). DOI: https://doi.org/10.5501/wjv.v13.i3.95349

Ahmed A, Fatima SS, Khan TA. Vitamin D3: the magical solution in the prevention of COVID-19. Adv Basic Med Sci. 2024;8(2):85-95.

Jolliffe DA, Camargo CA, Sluyter JD, Aglipay M, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2025;13(4):307-20. DOI: https://doi.org/10.1016/S2213-8587(24)00348-6

Pereira F, Fernandez-Barral A, Larriba MJ, Barbachano A, Gonzalez-Sancho JM. Vitamin D endocrine system in colorectal cancer. FEBS J. 2023;291(12):2485-518. DOI: https://doi.org/10.1111/febs.16955

Brust LA, Linxweiler M, Schnatmann J, Kuhn J, Knebel M, Braun FL, et al. Effects of vitamin D in head and neck squamous cell carcinoma. Biomed Pharmacother. 2024;180:117497. DOI: https://doi.org/10.1016/j.biopha.2024.117497

Sobhi P, Bahrami M, Mahdizadeh F, Fazaeli A, Babaei G, Rezagholizadeh L. Vitamin D and potential effects on cancers: a review. Mol Biol Rep. 2024;51(1):190. DOI: https://doi.org/10.1007/s11033-023-09111-y

Mot CI, Horhat DI, Balica NC, Hirtie B, Varga NI, Prodan-Barbulescu C, et al. Vitamin D and clinical outcomes in head and neck cancer: a systematic review. Nutrients. 2025;17(7):1100. DOI: https://doi.org/10.3390/nu17071100

Ucar N, Holick MF. Cutaneous vitamin D3 synthesis and its role in skin cancer prevention. Nutrients. 2025;17(3):386. DOI: https://doi.org/10.3390/nu17030386

Crnic T, Kasaj A. Association of vitamin D level and periodontitis: a comprehensive review. Periodontal Implant Res. 2024;8(1):14. DOI: https://doi.org/10.1007/s41894-024-00143-6

Meghil MM, Cutler CW. Influence of vitamin D on periodontal inflammation. Pathogens. 2023;12(9):1180. DOI: https://doi.org/10.3390/pathogens12091180

Lu EMC. Role of vitamin D in periodontal health and disease. J Periodontal Res. 2023;58(2):213-24. DOI: https://doi.org/10.1111/jre.13083

Bose A, Narayan SJ, Santosh HN. Reinforcement of epithelial barrier function by vitamin D in chronic periodontitis: RCT. RGUHS J Dent Sci. 2022;14(3). DOI: https://doi.org/10.26715/rjds.14_3_12

Chen X, Arias Z, Omori K, Yamamoto T, Shinoda-Ito Y, Takashiba S. Autophagy as mechanism of vitamin D action on periodontitis. BMC Oral Health. 2023;23(1):90. DOI: https://doi.org/10.1186/s12903-023-02802-9

Forouhari A, Heidari-Beni M, Veisi S, Poursafa P, Kelishadi R. Effect of epigenetics on vitamin D levels: systematic review. Arch Public Health. 2023;81(1). DOI: https://doi.org/10.1186/s13690-023-01122-2

Al-Taee ZM, Naji NM, Alwan ZHO, Al-Maamori AM, Mahdi RK. Vitamin D receptor (VDR) and autoimmune diseases. Hilla Univ Coll J Med Sci. 2025;3(2):31-7. DOI: https://doi.org/10.62445/2958-4515.1054

Downloads

Published

2025-12-04

How to Cite

Naqvi, A. S., Saeed, S., Subzwari, M., & Naqvi, A. B. (2025). Beyond the bones: the genomic and clinical landscape of vitamin D deficiency. International Journal Of Community Medicine And Public Health, 13(1), 505–514. https://doi.org/10.18203/2394-6040.ijcmph20254079

Issue

Section

Review Articles