Vitamin D: Sources, Metabolism, Mechanism of Action, and Its Role in Health and Disease

International Journal of Nursing and Health Science |
© 2025 by SSRG - IJNHS Journal |
Volume 11 Issue 1 |
Year of Publication : 2025 |
Authors : Munira Haque, Md. Nur Mohammad Sagor |
How to Cite?
Munira Haque, Md. Nur Mohammad Sagor, "Vitamin D: Sources, Metabolism, Mechanism of Action, and Its Role in Health and Disease," SSRG International Journal of Nursing and Health Science, vol. 11, no. 1, pp. 16-23, 2025. Crossref, https://doi.org/10.14445/24547484/IJNHS-V11I1P103
Abstract:
Vitamin D(VD), which is accepted widely to function as both a hormone and a vitamin, plays a crucial role in maintaining normal physiological processes. Its potential to mitigate disease severity has garnered significant scientific interest. Studies across various cell lines, animal models, and human populations have highlighted its extensive protective effects on multiple systems, including brain function, cardiac health, muscle and bone metabolism, immune response, mitochondrial integrity, and cellular interactions. Additionally, vitamin D has become a potent activator in human reproduction, pregnancy, and cancer regulation, underscoring its broad biological significance. This review compiles the multifaceted roles of vitamin D and its therapeutic potential in health and disease.
Keywords:
Immunity, Inflammation, Mitochondria, Reproduction, VD/VDR.
References:
[1] Michal A. Żmijewski, “Nongenomic Activities of Vitamin D,” Nutrients, vol. 14, no. 23, pp. 1-20, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[2] Guido Gembillo et al., “Protective Role of Vitamin D in Renal Tubulopathies,” Metabolites, vol. 10, no. 3, pp. 1-15, 2020.
[CrossRef] [Google Scholar] [Publisher Link]
[3] Elena M. V. de Cavanagh, Felipe Inserra, and Leon Ferder, “Angiotensin II Blockade: How its Molecular Targets May Signal to Mitochondria and Slow Aging. Coincidences with Calorie Restriction and mTOR Inhibition,” American Journal of Physiology – Heart and Circulatory Physiology, vol. 309, no. 1, pp. H15 - H44, 2015.
[CrossRef] [Google Scholar] [Publisher Link]
[4] Rui Chen et al., “Prostate Cancer Risk Prediction Models in Eastern Asian Populations: Current Status, Racial Difference, and Future Directions,” Asian Journal of Andrology, vol. 22, no. 2, pp. 158-161, 2020.
[CrossRef] [Google Scholar] [Publisher Link]
[5] Faruk Ahmed et al., “Prevalence and Predictors of Vitamin D Deficiency and Insufficiency Among Pregnant Rural Women in Bangladesh,” Nutrients, vol. 13, no. 2, pp. 1-16, 2021.
[CrossRef] [Google Scholar] [Publisher Link]
[6] Christine M. Latham et al., “Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health,” Frontiers Physiology, vol. 12, pp. 1-12, 2021.
[CrossRef] [Google Scholar] [Publisher Link]
[7] Jerome Salles et al., “Vitamin D Status Modulates Mitochondrial Oxidative Capacities in Skeletal Muscle: Role in Sarcopenia,” Communications Biology, vol. 5, pp. 1-15, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[8] Mario Romani, Mette M. Berger, and Patrizia D’amelio, “From the Bench to the Bedside: Branched Amino Acid and Micronutrient Strategies to Improve Mitochondrial Dysfunction Leading to Sarcopenia,” Nutrients, vol. 14, no. 3, pp. 1-19, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[9] Alavala Matta Reddy et al., “Pivotal Role of Vitamin D in Mitochondrial Health, Cardiac Function, and Human Reproduction,” EXCLI Journal, vol. 21, pp. 967-990, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[10] Istvan Bókkon et al., “COVID-19: The Significance of Platelets, Mitochondria, Vitamin D, Serotonin and the Gut Microbiota,” Current Medicinal Chemistry, vol. 28, no. 37, pp. 7634-7657, 2021.
[CrossRef] [Google Scholar] [Publisher Link]
[11] A.M. Olszewska, and M.A. Zmijewski, “Genomic and Non-genomic Action of Vitamin D on Ion Channels – Targeting Mitochondria,” Mitochondrion, vol. 77, pp. 1-15, 2024.
[CrossRef] [Google Scholar] [Publisher Link]
[12] Piotr Zabul et al., “A Proposed Molecular Mechanism of High-dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia,” International Journal of Molecular Sciences, vol. 16, no. 6, pp. 13043-13064, 2015.
[CrossRef] [Google Scholar] [Publisher Link]
[13] Maurizio Cutolo et al., “Involvement of the Secosteroid Vitamin D in Autoimmune Rheumatic Diseases and COVID-19,” Nature Reviews Rheumatology, vol. 19, pp. 265-287, 2023.
[CrossRef] [Google Scholar] [Publisher Link]
[14] Cristina Russo et al., “Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health,” Biomedicines, vol. 10, no. 4, pp. 1-19, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[15] Ming-Jse Lee et al., “Vitamin D Deficiency in Northern Taiwan: A Community-based Cohort Study,” BMC Public Health, vol. 19, pp. 1 8, 2019.
[CrossRef] [Google Scholar] [Publisher Link]
[16] Sylvia Christakos et al., “Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects,” Physiological Reviews, vol. 96, no. 1, pp. 365-408, 2015.
[CrossRef] [Google Scholar] [Publisher Link]
[17] Benjamin Chun-Kit Tong, “Neonatal Rat Myocardial Extraction HHS Public Access,” Physiological Behaviour, vol. 176, no. 1, pp. 139 148, 2018.
[Google Scholar]
[18] Mengli Yu et al., “Vitamin D Receptor Inhibits EMT Via Regulation of the Epithelial Mitochondrial Function in Intestinal Fibrosis,” Journal of Biological Chemistry, vol. 296, pp. 1-16, 2021.
[CrossRef] [Google Scholar] [Publisher Link]
[19] Andrzej T. Slominski et al., “Photoprotective Properties of Vitamin D and Lumisterol Hydroxyderivatives,” Cell Biochemistry and Biophysics, vol. 78, pp. 165-180, 2020.
[CrossRef] [Google Scholar] [Publisher Link]
[20] Madeline P. Sheeley et al., “Vitamin D Regulation of Energy Metabolism in Cancer,” British Journal of Pharmacology, vol. 179, no. 12, pp. 2890-2905, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[21] Drew A. Glencross, Charlotte Cheadle, and Catherine M. Hawrylowicz, “Vitamin D and Adaptive Immunity in Health and Disease,” Feldman Pike’s Vitamin D, pp. 1035-1056, 2024.
[CrossRef] [Google Scholar] [Publisher Link]
[22] I. Nemere et al., “Identification of a Specific Binding Protein for 1α, 25-Dihydroxyvitamin D3 in Basal-lateral Membranes of Chick Intestinal Epithelium and Relationship to Transcaltachia,” Journal of Biological Chemistry, vol. 269, no. 38, pp. 23750-23756, 1994.
[CrossRef] [Google Scholar] [Publisher Link]
[23] Duygu Gezen-Ak, and Erdinc Dursun, “Vitamin D, A Secosteroid Hormone and Its Multifunctional Receptor, Vitamin D Receptor, in Alzheimer’s Type Neurodegeneration,” Journal of Alzheimer’s Disease, vol. 95, no. 4, pp. 1273-1299, 2023.
[CrossRef] [Google Scholar] [Publisher Link]
[24] Nami Safai Haeri, Subashan Perera, and Susan L. Greenspan, “The Association of Vitamin D with Bone Microarchitecture, Muscle Strength, and Mobility Performance in Older Women in Long-term Care,” Bone, vol. 176, 2023.
[CrossRef] [Google Scholar] [Publisher Link]
[25] Jingxin Yang et al., “The Protective Effect of 1,25(OH)2D3 on Myocardial Function is Mediated via Sirtuin 3-Regulated Fatty Acid Metabolism,” Frontiers in Cell and Developmental Biology, vol. 9, pp. 1-14, 2021.
[CrossRef] [Google Scholar] [Publisher Link]
[26] Eugene Chang, and Yangha Kim, “Vitamin D Ameliorates Fat Accumulation with AMPK/SIRT1 Activity in C2C12 Skeletal Muscle Cells,” Nutrients, vol. 11, no. 11, pp. 1-17, 2019.
[CrossRef] [Google Scholar] [Publisher Link]
[27] Eugene Chang, “1, 25-Dihydroxyvitamin D Decreases Tertiary Butyl-hydrogen Peroxide-induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells,” Molecules, vol. 24, no. 21, pp. 1-14, 2019.
[CrossRef] [Google Scholar] [Publisher Link]
[28] Zachary C. Ryan et al., 1α, 25-Dihydroxyvitamin D3 Mitigates Cancer Cell Mediated Mitochondrial Dysfunction in Human Skeletal Muscle Cells,” Biochemical and Biophysical Research Communications, vol. 496, no. 2, pp. 746-752, 2018.
[CrossRef] [Google Scholar] [Publisher Link]
[29] Justine Vanhevel et al., “The Combination of the CDK4/6 Inhibitor, Palbociclib, With the Vitamin D3 Analog, Inecalcitol, Has Potent In Vitro and In Vivo Anticancer Effects in Hormone-Sensitive Breast Cancer, But Has a More Limited Effect in Triple-Negative Breast Cancer,” Frontiers in Endocrinology, vol. 13, pp. 1-17, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[30] Tianbao Yao et al., “Vitamin D Receptor Activation Protects Against Myocardial Reperfusion Injury through Inhibition of Apoptosis and Modulation of Autophagy,” Antioxidants & Redox Signaling, vol. 22, no. 8, 2014.
[CrossRef] [Google Scholar] [Publisher Link]
[31] Jazmin E. Hawes et al., “Maternal Vitamin D Deficiency Alters Fetal Brain Development in the BALB/c Mouse,” Behavioural Brain Research, vol. 286, pp. 192-200, 2015.
[CrossRef] [Google Scholar] [Publisher Link]
[32] Zhaoxin Hu et al., “VDR Activation Attenuate Cisplatin Induced AKI by Inhibiting Ferroptosis,” Cell Death & Disease, vol. 11, pp. 1 11, 2020.
[CrossRef] [Google Scholar] [Publisher Link]
[33] Francesca Silvagno, and Loredana Bergandi, “Editorial of Special Issue ‘The Role of Vitamin D in Human Health and Diseases 3.0,” International Journal of Molecular Sciences, vol. 25, no. 13, pp. 1-3, 2024.
[CrossRef] [Google Scholar] [Publisher Link]
[34] Jiawei Xu et al., “Neurosteroids: A Novel Promise for the Treatment of Stroke and Post-stroke Complications,” Journal of Neurochemistry, vol. 160, no. 1, pp. 113-127, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[35] Giulia Bivona et al., “Non-skeletal Activities of Vitamin D: From Physiology to Brain Pathology,” Medicina, vol. 55, no. 7, pp. 1-9, 2019.
[CrossRef] [Google Scholar] [Publisher Link]
[36] Shreeya S. Navale et al., “Vitamin D and Brain Health: An Observational and Mendelian Randomization Study,” American Journal of Clinical Nutrion, vol. 116, no. 2, pp. 531-540, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[37] Alessandra Mirarchi et al., “Microglia and Brain Disorders: The Role of Vitamin D and Its Receptor,” International Journal of Molecular Sciences, vol. 24, no. 15, pp. 1-21, 2023.
[CrossRef] [Google Scholar] [Publisher Link]
[38] Rai-Hua Lai et al., “Vitamin D Supplementation Worsens Alzheimer’s Progression: Animal Model and Human Cohort Studies,” Aging Cell, vol. 21, no. 8, pp. 1-13, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[39] Wencui Zhang et al., “Vitamin D3 Attenuates Neuropathic Pain via Suppression of Mitochondria-Associated Ferroptosis by Inhibiting PKCα/NOX4 Signaling Pathway,” CNS Neuroscience & Therapeutics, vol. 30, no. 9, pp. 1-17, 2024.
[CrossRef] [Google Scholar] [Publisher Link]
[40] Lidia Saidi et al., “Maternal Vitamin D Deficiency and Brain Functions: A Never-ending Story,” Food & Functions, vol. 14, pp. 6290 6301, 2023.
[CrossRef] [Google Scholar] [Publisher Link]
[41] Amarpreet Sangha et al., “The Role of Vitamin D in Neuroprotection in Multiple Sclerosis: An Update,” Nutrients, vol. 15, no. 13, pp. 1 15, 2023.
[CrossRef] [Google Scholar] [Publisher Link]
[42] Xiaoying Cui, and Darryl W. Eyles, “Vitamin D and The Central Nervous System: Causative and Preventative Mechanisms in Brain Disorders,” Nutrients, vol. 14, no. 20, pp. 1-20, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[43] Jinhui Hu et al., “Vitamin D Ameliorates Apoptosis and Inflammation by Targeting the Mitochondrial and MEK1/2-ERK1/2 Pathways in Hyperoxia-Induced Bronchopulmonary Dysplasia,” Journal of Inflammation Research, vol. 15, pp. 4891-4906, 2022.
[CrossRef] [Google Scholar] [Publisher Link]
[44] Jin-Lu Ji et al., “Immunological Function of Vitamin D During Human Pregnancy,” American Journal of Reproductive Immunology, vol. 78, no. 2, 2017.
[CrossRef] [Google Scholar] [Publisher Link]
[45] Gyu Hee Kim et al., “Vitamin D Ameliorates Age-induced Nonalcoholic Fatty Liver Disease by Increasing the Mitochondrial Contact Site and Cristae Organizing System (MICOS) 60 Level,” Experimental & Molecular Medicine, vol. 56, pp. 142-155, 2024.
[CrossRef] [Google Scholar] [Publisher Link]
[46] Tommaso Raiteri et al., “The Atrophic Effect of 1,25(OH)2 Vitamin D3 (Calcitriol) on C2C12 Myotubes Depends on Oxidative Stress,” Antioxidants, vol. 10, no. 12, pp. 1-19, 1980.
[CrossRef] [Google Scholar] [Publisher Link]
[47] Marco Consiglio et al., “The Vitamin D Receptor Inhibits the Respiratory Chain, Contributing to the Metabolic Switch that is Essential for Cancer Cell Proliferation,” PLoS One, vol. 9, no. 12, pp. 1-23, 2014.
[CrossRef] [Google Scholar] [Publisher Link]
[48] Melinda Fernando et al., “Vitamin D-binding Protein in Pregnancy and Reproductive Health,” Nutrients, vol. 12, no. 5, pp. 1-30, 2020.
[CrossRef] [Google Scholar] [Publisher Link]
[49] Michael A. Zmijewski, “Vitamin D and Human Health,” International Journal of Molecular Sciences, vol. 20, no. 1, pp. 1-6, 2019.
[CrossRef] [Google Scholar] [Publisher Link]
[50] Sang-Min Jeon, and Eun-Ae Shin, “Exploring Vitamin D Metabolism and Function in Cancer,” Experimental & Molecular Medicine, vol. 50, pp. 1-14, 2018.
[CrossRef] [Google Scholar] [Publisher Link]
[51] Emanuele Rinninella et al., “Vitamin D and Colorectal Cancer: Chemopreventive Perspectives through the Gut Microbiota and The Immune System,” BioFactors, vol. 48, no. 2, pp. 285-293, 2022.
[CrossRef] [Google Scholar] [Publisher Link]