Let’s talk about Vitamin D
Updated: Feb 13, 2021
As soon as someone mentions Vitamin D, people immediately think about bone health. It’s correct that Vitamin D does play a major role in this, but did you know that is also plays other roles in the body that most of the general population don’t known about? Let’s do a little breakdown of this nutrient.
What is Vitamin D?
Often called a vitamin, Vitamin D is in actual fact a hormone. Produced in the skin from a 7-dehydrocholesterol (a cholesterol precursor also known as pro-vitamin D), vitamin D has to go through 3 stages in order to reach its active form. Upon exposure to UVB light from the sun, 7-dehydrocholesterol is converted to cholecalciferol, the form that is tested when you have a blood test. Cholecalciferol is then transported to the liver, where it is converted to 25-hydroxyvitamin D3 (calcidiol). Finally, 25-hydroxyvitamin D3 reaches the kidneys, where it is converted to 1,25-dihydroxy vitamin D3 (calcitriol), the active form. Individuals with chronic kidney disease and severe liver disease may have compromised conversion of vitamin D, especially as these organs are required to reach its active form. To a lesser extent, vitamin D can also be found in foods including eggs, meats, fish, mushrooms, and some fortified foods, and in supplements, although these need to be converted to the active form.
What roles does Vitamin D play?
Vitamin D is an extremely powerful hormone and is known to play a variety of roles in maintaining homeostasis across bodily systems. This is because the vitamin D receptor (VDR) is expressed on the nucleus of cells throughout the human body including those found in the intestine, bone, skin, kidney, parathyroid glands, and the immune, cardiovascular, endocrine, reproductive, and nervous systems.
Vitamin D’s classically known function is its role in the maintenance of bone and skeletal health via calcium homeostasis, bone formation/mineralisation, and bone resorption. Skeletal conditions associated with vitamin D deficiency include rickets in children and osteomalacia in adults, which result in brittle bones due to defective bone mineralisation. Vitamin D deficiency may also be seen in individuals with osteoporosis, although this is mostly associated with calcium deficiency, inactivity/disuse, old age, endocrine imbalances, or alcoholism, which cause reduced bone mass overall with normal mineralisation. Recent research also suggests that vitamin D plays a role in skeletal muscle metabolism and function, especially through improved protein synthesis, muscle cell proliferation and differentiation, and oxygen consumption. Individuals with low levels of vitamin D may experience muscle atrophy, pain, and weakness, with an increased risk of sarcopenia and falls.
Infections and Autoimmune/Inflammatory Diseases
Vitamin D deficiency has been associated with numerous chronic conditions related to increased inflammation and immune dysregulation including autoimmune diseases, diabetes, cardiovascular disease, and asthma. Deficiency may also increase an individual’s susceptibility to infection. VDR expression is seen in majority of immune cells of both the innate and adaptive immune systems, including B lymphocytes, T lymphocytes, monocytes, macrophages, and dendritic cells.
Through its ability to modulate the innate and adaptive immune systems, vitamin D may assist in the prevention and treatment of infections via its ability to influence the production of endogenous antimicrobial compounds and regulate the inflammatory cascade. Research suggests that vitamin D deficiency has been associated with an increased severity and risk of acquiring an infection, especially within the respiratory tract.
Sufficient vitamin D levels have been associated with controlling the level of inflammation seen in autoimmune diseases, especially Rheumatoid Arthritis, Systemic Sclerosis, Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathies, Inflammatory Bowel Disease, Multiple Sclerosis, and Type 1 Diabetes. Current evidence suggests vitamin D may inhibit the pro-inflammatory activity and proliferation of T-Helper 1 cells, whilst promoting the responses of T-Helper 2 cells. An imbalance in the TH1 and TH2 cell cytokine profile has been associated with the development and progression of autoimmune conditions.
Vitamin D deficiency may play a role in the progression of Type 2 Diabetes due to the downregulation of VDRs in the pancreatic β-cells and thus, may contribute to dysfunctional insulin secretion. Deficiency has also been linked to numerous cardiovascular risk factors including through the development of insulin resistance and metabolic syndrome, an abnormal lipid profile, hypertension, and compromised endothelial integrity. Finally, vitamin D deficiency has been associated with increased inflammation and exacerbations, decreased lung function, and poorer health outcomes in individuals with asthma. By binding to the VDR, Vitamin D may decrease asthma-associated inflammation, and reduce the proliferation of airway smooth muscle cells, the production of proinflammatory cytokines, and the secretion of mucous.
Vitamin D has been shown to play roles in supporting both male and female fertility. VDRs have been found in various cells of the male reproductive tract, as well as in tissues of the female reproductive tract including the ovaries, endometrium, and placenta. Some evidence suggests that adequate levels of vitamin D may support testicular function, sperm motility, and spermatogenesis. In the female reproductive tract, vitamin D plays a major role in the production and regulation of hormones via the VDR. In women with Polycystic Ovarian Syndrome, vitamin D deficiency may exacerbate the condition. Adequate levels of vitamin D may be positively associated with enhanced progesterone production.
Vitamin D deficiency may be a risk factor for the development of depression. This is thought to be via its ability to alter neurotransmitters within the brain, especially as VDRs are found to be expressed in neurotransmitter pathways affecting the synthesis of serotonin and dopamine. Consequently, this may lead to a disruption in pathways involved with motivation, pleasure, and reward. In addition to this, it is proposed that depression may be associated with the upregulation of inflammation, which can result in a decreased production of neurotransmitters including serotonin, the neurotransmitter that when depleted, is thought to contribute to a low mood. Vitamin D may express neuroprotective qualities via its anti-inflammatory effects.
The Bottom Line
Being synthesised from a cholesterol precursor in the skin, vitamin D synthesis involves 3 stages that require adequate functioning of the liver and kidneys. In the diet, it is found in animal foods, irradiated mushrooms, and fortified foods and still requires 2 more steps to reach its active form. Vitamin D plays roles in multiple systems across the body, including the musculoskeletal, integumentary, gastrointestinal, immune, nervous, reproductive, and endocrine systems. Deficiency of this hormone may be implicated in conditions including bone health, muscle health, autoimmune diseases, type 2 diabetes, cardiovascular disease, asthma, infections, fertility, PCOS, and depression. The only way to assess your current levels is via a blood test. From here, if your levels are inadequate, you can work with your health practitioner to consider a supplementation regime that’s right for you.
Ali, N. S., & Nanji, K. (2017). A Review on the Role of Vitamin D in Asthma. Cureus. doi: 10.7759/cureus.1288
Aranow, C. (2011). Vitamin D and the Immune System. Journal of Investigative Medicine, 59(6), 881–886. doi: 10.2310/jim.0b013e31821b8755
Bretscher, P. (2019). On Analyzing How the Th1/Th2 Phenotype of an Immune Response Is Determined: Classical Observations Must Not Be Ignored. Frontiers in Immunology, 10. doi: 10.3389/fimmu.2019.01234
Cuomo, A., Giordano, N., Goracci, A., & Fagiolini, A. (2017). Depression and Vitamin D Deficiency: Causality, Assessment, and Clinical Practice Implications. Neuropsychiatry, 07(05). doi: 10.4172/neuropsychiatry.1000255
Danik, J. S., & Manson, J. E. (2012). Vitamin D and Cardiovascular Disease. Current Treatment Options in Cardiovascular Medicine, 14(4), 414–424. doi: 10.1007/s11936-012-0183-8
Dankers, W., Colin, E. M., Hamburg, J. P. V., & Lubberts, E. (2017). Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Frontiers in Immunology, 7. doi: 10.3389/fimmu.2016.00697
Gunville, C., Mourani, P., & Ginde, A. (2013). The Role of Vitamin D in Prevention and Treatment of Infection. Inflammation & Allergy-Drug Targets, 12(4), 239–245. doi: 10.2174/18715281113129990046
Hall, S. C., & Agrawal, D. K. (2017). Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years. Clinical Therapeutics, 39(5), 917–929. doi: 10.1016/j.clinthera.2017.04.002
Jolliffe, D. A., Greenberg, L., Hooper, R. L., Griffiths, C. J., Camargo, C. A., Kerley, C. P., … Martineau, A. R. (2017). Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. The Lancet Respiratory Medicine, 5(11), 881–890. doi: 10.1016/s2213-2600(17)30306-5
Keane, K. N., Cruzat, V. F., Calton, E. K., Hart, P. H., Soares, M. J., Newsholme, P., & Yovich, J. L. (2017). Molecular actions of vitamin D in reproductive cell biology. Reproduction, 153(1). doi: 10.1530/rep-16-0386
Kheiri, B., Abdalla, A., Osman, M., Ahmed, S., Hassan, M., & Bachuwa, G. (2018). Vitamin D deficiency and risk of cardiovascular diseases: a narrative review. Clinical Hypertension, 24(1). doi: 10.1186/s40885-018-0094-4
Kriegel, M. A., Manson, J. E., & Costenbader, K. H. (2011). Does Vitamin D Affect Risk of Developing Autoimmune Disease?: A Systematic Review. Seminars in Arthritis and Rheumatism, 40(6). doi: 10.1016/j.semarthrit.2010.07.009
Lappe, J. M. (2011). The Role of Vitamin D in Human Health: A Paradigm Shift. Journal of Evidence-Based Complementary & Alternative Medicine, 16(1), 58–72. doi: 10.1177/1533210110392952
Liu, J., Dong, Y.-Q., Yin, J., Yao, J., Shen, J., Sheng, G.-J., … Wu, W.-F. (2019). Meta-analysis of vitamin D and lung function in patients with asthma. Respiratory Research, 20(1). doi: 10.1186/s12931-019-1072-4
Martineau, A., Takeda, A., Nurmatov, U., Sheikh, A., & Griffiths, C. J. (2015). Vitamin D for the management of asthma. Cochrane Database of Systematic Reviews. doi: 10.1002/14651858.cd011511
Menon, B., Nima, G., Dogra, V., & Kaur, C. (2014). Low level of Vitamin D is associated with poor asthma control: a randomized control trial of Vitamin D supplementation in Asthma. Research, 1. doi: 10.13070/rs.en.1.1088
Montenegro, K. R., Carlessi, R., Cruzat, V., & Newsholme, P. (2019). Effects of vitamin D on primary human skeletal muscle cell proliferation, differentiation, protein synthesis and bioenergetics. The Journal of Steroid Biochemistry and Molecular Biology, 193, 105423. doi: 10.1016/j.jsbmb.2019.105423
Montenegro, K. R., Cruzat, V., Carlessi, R., & Newsholme, P. (2019). Mechanisms of vitamin D action in skeletal muscle. Nutrition Research Reviews, 32(2), 192–204. doi: 10.1017/s0954422419000064
Nair, S. (2010). Vitamin D Deficiency and Liver Disease. Gatroenterology & Hepatology , 6(8), 491–493. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950664/
Nakashima, A., Yokoyama, K., Yokoo, T., & Urashima, M. (2016). Role of vitamin D in diabetes mellitus and chronic kidney disease. World Journal of Diabetes, 7(5), 89. doi: 10.4239/wjd.v7.i5.89
Pike, J. W., Meyer, M. B., Lee, S.-M., Onal, M., & Benkusky, N. A. (2017). The vitamin D receptor: contemporary genomic approaches reveal new basic and translational insights. Journal of Clinical Investigation, 127(4), 1146–1154. doi: 10.1172/jci88887
Sassi, F., Tamone, C., & D’Amelio, P. (2018). Vitamin D: Nutrient, Hormone, and Immunomodulator. Nutrients, 10(11), 1656. doi: 10.3390/nu10111656
Schaad, K. A., Bukhari, A. S., Brooks, D. I., Kocher, J. D., & Barringer, N. D. (2019). The relationship between vitamin D status and depression in a tactical athlete population. Journal of the International Society of Sports Nutrition, 16(1). doi: 10.1186/s12970-019-0308-5
Trombetta, A. C., Paolino, S., & Cutolo, M. (2018). Vitamin D, Inflammation and Immunity: Review of Literature and Considerations on Recent Translational and Clinical Research Developments. The Open Rheumatology Journal, 12(1), 201–213. doi: 10.2174/1874312901812010201
Verduijn, J., Milaneschi, Y., Schoevers, R. A., Hemert, A. M. V., Beekman, A. T. F., & Penninx, B. W. J. H. (2015). Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression. Translational Psychiatry, 5(9). doi: 10.1038/tp.2015.137
Yang, C.-Y., Leung, P. S. C., Adamopoulos, I. E., & Gershwin, M. E. (2013). The Implication of Vitamin D and Autoimmunity: a Comprehensive Review. Clinical Reviews in Allergy & Immunology, 45(2), 217–226. doi: 10.1007/s12016-013-8361-3