Vitamin D refers to two compounds, vitamin D2 ergocalciferol and vitamin D3 cholecalciferol .  Vitamin D2 derives from irradiation of the plant sterol, ergosterol, and i ...

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Vitamin D refers to two compounds, vitamin D2 ergocalciferol and vitamin D3 cholecalciferol . 

Vitamin D2 derives from irradiation of the plant sterol, ergosterol, and is provided by the diet. Vitamin D3 originates from a cutaneous compound by endogenous synthesis. Vitamin D was initially described at the time of the industrial revolution, when England faced rickets; since then, the relation between vitamin D and calcium-phosphorus metabolism has never been discussed. However, over the last four decades, other activities of vitamin D have been highlighted. Actually, vitamin D is considered as a neurohormone that regulates cell growth and proliferation and immunomodulation (1).

Vitamin D and kidney

Calcium and phosphorus are essential minerals required for many critical biologic functions including cell signaling, energy metabolism, skeletal growth and integrity. Calcium and phosphate homeostasis are maintained primarily by regulation of epithelial calcium and phosphate cotransport in the kidney and intestine, processes that are tightly regulated by hormones including 1,25 dihydroxyvitamin D (1,25(OH)2D), fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). In patients with chronic kidney disease (CKD), as renal function declines, disruption of feedback loops between these hormones have adverse consequences on several organ systems, including the skeleton, heart and vascular system. CKD-associated mineral and bone disorder (CKD-MBD) is defined as a systemic disorder of mineral and bone metabolism due to CKD manifested by abnormalities of calcium, phosphorus, PTH or vitamin D metabolism, abnormalities of bone turnover, mineralization and volume, and ectopic soft tissue calcification. Complications of CKD-MBD include vascular calcification, stroke, skeletal fracture and increased risk of death. Increased FGF23 and PTH concentrations, and 1,25(OH)2D deficiency contribute to the pathogenesis of CKD-MBD. Therefore, treatment of patients with CKD-MBD is focused on restoring the feedback loops to maintain normal calcium and phosphate balance to prevent skeletal and cardiovascular complications (2).

Vitamin D, bones and muscle

Bone is not the only target of vitamin D. The review by Gunton and Girgis focuses on muscle (Gunton, n.d.). Muscle weakness is a well known symptom of vitamin D deficiency, but whether fully differentiated myocytes contain the vitamin D receptor, and so are direct targets of 1,25(OH)2D, remains controversial. However, this article provides evidence that it is. Moreover, this article provides a balanced and extensive review of the RCTs that have examined the impact of vitamin D supplementation on muscle function and falls as they reach the overall conclusion that although “vitamin D supplementation generally reduces the risk of falls in frail, older individuals (at doses > 700 IU d), dose-dependent effects have not been clearly established with the exception of a significantly higher risk of falls in subjects receiving single mega-doses”. Perwad focuses on the kidney with particular attention to the pathologic events disrupting bone and mineral homeostasis in patients with chronic kidney disease (CKD) (Perwad, n.d.). Although numerous disturbances to bone and mineral metabolism develop with the onset and progression of CKD, the roles of FGF23, PTH, and 1,25(OH)2D are high on the list. In this article Perwad reviews the key role that the kidney plays in vitamin D metabolism and calcium and phosphate handling, the regulation of such processes by PTH and FGF23, how CKD disrupts these processes leading to bone disease and vascular calcification, and the difficulties in managing such patients (3).

Vitamin D and cancer

The vitamin D receptor is expressed in most tissues of the body – and the cancers that arise from those tissues. The vitamin D signaling pathway is active in those tissues and cancers. This is at least consistent with the hypothesis that perturbing this signaling may have a favorable effect on the genesis and growth of cancers. Epidemiologic data indicate that vitamin D signaling may be important in the initiation and outcome of a number of types of cancer. Many studies have shown that calcitriol (1,25 dihydroxycholecalciferol) and other vitamin D compounds have antiproliferative, pro-apoptotic, anti-cell migration and antiangiogenic activity in a number of preclinical studies in many different cancer types. Unfortunately, the assessment of the activity of calcitriol or other vitamin D analogues in the treatment of cancer, as single agents or in combination with other anticancer agents has been stymied by the failure to adhere to commonly accepted principles of drug development and clinical trials conduct (4).

Other studies

Antimicrobial and Immune-Modulatory Effects of Vitamin D Provide Promising Antibiotics-Independent Approaches to Tackle Bacterial Infections - Lessons Learnt from a Literature Survey.  Golpour A, Bereswill S, Heimesaat MM.  Eur J Microbiol Immunol (Bp). 2019 Aug 13;9(3):80-87. doi: 10.1556/1886.2019.00014

Managing vitamin D deficiency in inflammatory bowel disease.  Nielsen OH, Hansen TI, Gubatan JM, Jensen KB, Rejnmark L.  Frontline Gastroenterol. 2019 Oct;10(4):394-400. doi: 10.1136/flgastro-2018-101055.

Vitamin D and the Intestine: Review and Update.  Christakos S, Li S, De La Cruz J, Shroyer NF, Criss ZK, Verzi MP, Fleet JC.  J Steroid Biochem Mol Biol. 2019 Oct 23:105501. doi: 10.1016/j.jsbmb.2019.105501.

Vitamin D as A Protector of Arterial Health: Potential Role in Peripheral Arterial Disease Formation.  Krishna SM.  Int J Mol Sci. 2019 Oct 3;20(19). pii: E4907. doi: 10.3390/ijms20194907

Molecular Formula : C₂₈H₄₄O 

Molecular Weight : 396.659

CAS :   8017-28-5

References_________________ 

(1) Vitamin D deficiency might pose a greater risk for ApoEɛ4 non-carrier Alzheimer's disease patients.
Dursun E, Alaylıoğlu M, Bilgiç B, Hanağası H, Lohmann E, Atasoy IL, Candaş E, Araz ÖS, Önal B, Gürvit H, Yılmazer S, Gezen-Ak D.
Neurol Sci. 2016 Jun 29.

(2) Vitamin D and kidney disease.
Keung L, Perwad F.
Bone Rep. 2018 Jul 25;9:93-100. doi: 10.1016/j.bonr.2018.07.002. 

(3) Vitamin D and bone and beyond.
Bikle DD, Bouillon R.
Bone Rep. 2018 Jul 4;9:120-121. doi: 10.1016/j.bonr.2018.07.003.

(4) Calcitriol and cancer therapy: A missed opportunity.
Trump DL.
Bone Rep. 2018 Jun 13;9:110-119. doi: 10.1016/j.bonr.2018.06.002.

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