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Topic Review
Vitamin D and Rheumatic Diseases
Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40–60 ng/mL (100–150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.
  • 638
  • 22 Nov 2021
Topic Review
Vitamin D and Preeclampsia
Preeclampsia (PE) is a set of clinical symptoms that appears after the 20th week of pregnancy. It is a multi-organ disease characterized by hypertension and proteinuria, and in the absence of proteinuria—an impairment of the functions of the internal organs. With regard to the multiple mechanisms of action of Vit D, its deficiency seems to be one of the possible factors conducive to PE development. It has been suggested that the consequence of low Vit D levels may be the appearance of an early, severe form of PE, and its supplementation may be a protective factor against its recurrence in subsequent pregnancies [232]. The relationship between Vit D and PE development may explain its impact on implantation, angiogenesis, and endothelial status, regulation of the immune response, effect on RAAS, and calcium metabolism. 
  • 572
  • 17 Nov 2021
Topic Review
Vitamin D and Non-Melanoma Skin Cancer
Non-melanoma skin cancers (NMSC) are the most common type of skin malignancies among humans (particularly fair-skinned populations of European descent) and its incidence rates have been on the rise globally for decades [1]. The best defined role of vitamin D in humans is in supporting the normal development and maintenance of bone tissues and in regulating calcium metabolism [7,8]. Furthermore, there is growing evidence that vitamin D plays a role in many fundamental biological processes (e.g., cell proliferation, angiogenesis, and modulation of the immune system) [9] implicated in carcinogenesis. 
  • 374
  • 26 Oct 2021
Topic Review
Vitamin D and Microbiota
Microbiome studies have already demonstrated unique microbial patterns in systemic autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus. Dysbiosis also seems to be associated with allergies, in particular asthma, atopic dermatitis, and food allergy.
  • 334
  • 28 Oct 2022
Topic Review
Vitamin D and Its Neuroimmunological Roles
Vitamin D consists of a group of structurally related secosteroids, including cholecalciferol, ergocalciferol, 25-hydroxyvitamin D (25(OH)D, calcidiol), and 1,25-dihydroxyvitamin D (1,25(OH)2D, calcitriol). Vitamin D, a fat-soluble neuroactive prohormone, is increasingly recognized as not only a marker of overall health but also a necessary neurosteroid and immunomodulator, exerting pleiotropic effects on the neurological system. 
  • 167
  • 15 Sep 2023
Topic Review
Vitamin D and Inflammation in Obesity
Obesity affects more than one billion people worldwide and often leads to cardiometabolic chronic comorbidities. It induces senescence-related alterations in adipose tissue, and senescence is closely linked to obesity. Fully elucidating the pathways through which vitamin D exerts anti-inflammatory effects may improve our understanding of local adipose tissue inflammation and the pathogenesis of metabolic disorders.
  • 187
  • 02 Jan 2024
Topic Review
Vitamin D and Infertility
Vitamin D plays a crucial role in calcium and phosphate homeostasis, by increasing intestinal calcium absorption and renal calcium reabsorption.  For vitamin D, accumulating evidence from observational human studies suggests a key role for both male and female fertility.
  • 496
  • 03 Sep 2021
Topic Review
Vitamin D and Infectious Diseases
It is now 2 years since we have seen the impact of the CoronaVirus Disease-19 (COVID-19) caused by Syndrome-Coronavirus-2 worldwide, affecting millions of people and rates of mortality close to 6 million. Although we are beginning to see the real benefit of vaccines, in terms of reduced mortality rates, many individuals still remain to be vaccinated or do not respond to them leaving a large number of patients still experiencing severe respiratory symptoms associated with COVID-19. In recent months, we have seen another surge in individuals infected with COVID-19 and mortality rates are also increasing. In the absence of effective therapies or vaccines, the medical and scientific community have extensively explored a range of current available therapeutic agents, mainly focused on targeting viral replication as well as managing severe respiratory symptoms associated with COVID-19.  Vitamin D has emerged as one such candidate due to its recognized immunomodulatory effects. In this regard, the activation of the vitamin D receptor (VDR) signaling pathway may generate beneficial effects in acute respiratory distress syndrome by decreasing the cytokine/chemokine storm, thus having an important immunomodulatory and anti-inflammatory role.
  • 528
  • 07 Feb 2022
Topic Review
Vitamin D and Glomerulonephritis
Vitamin D presents a plethora of different functions that go beyond its role in skeletal homeo-stasis. It is an efficient endocrine regulator of the Renin–Angiotensin–Aldosterone System (RAAS) and erythropoiesis, exerts immunomodulatory effects, reduces the cardiovascular events and all-cause mortality. In Chronic Kidney Disease (CKD) patients, Vitamin D function is im-paired; the renal hydrolyzation of its inactive form by the action of 1α-hydroxylase declines at the same pace of reduced nephron mass. Moreover, Vitamin D major carrier, the D-binding pro-tein (DBP), is less represented due to Nephrotic Syndrome (NS), proteinuria, and the alteration of the cubilin–megalin–amnionless receptor complex in the renal proximal tubule. In Glomeru-lonephritis (GN), Vitamin D supplementation demonstrated to significantly reduce proteinuria and to slow kidney disease progression. It also has potent antiproliferative and immunomodu-lating functions, contributing to the inhibitions of kidney inflammation. Vitamin D preserves the structural integrity of the slit diaphragm guaranteeing protective effects on podocytes. Acti-vated Vitamin D has been demonstrated to potentiate the antiproteinuric effect of RAAS inhibi-tors in IgA nephropathy and Lupus Nephritis, enforcing its role in the treatment of glomerulo-nephritis: calcitriol treatment, through Vitamin D receptor (VDR) action, can regulate the hepa-ranase promoter activity and modulate the urokinase receptor (uPAR), guaranteeing podocyte preservation. It also controls the podocyte distribution by modulating mRNA synthesis and protein expression of nephrin and podocin. Maxalcalcitol is another promising alternative: it has about 1/600 affinity to vitamin D binding protein (DBP), compared to Calcitriol, overcoming the risk of hypercalcemia, hyperphosphatemia and calcifications, and it circulates principally in un-bound form with easier availability for target tissues. Doxercalciferol, as well as paricalcitol, showed a lower incidence of hypercalcemia and hypercalciuria than Calcitriol. Paricalcitol demonstrated a significant role in suppressing RAAS genes expression: it significantly decreases angiotensinogen, renin, renin receptors, and vascular endothelial growth factor (VEGF) mRNA levels, thus reducing proteinuria and renal damage.
  • 747
  • 11 Oct 2021
Topic Review
Vitamin D and Endothelial Function
Vitamin D deficiency (VDD) and erectile dysfunction (ED) heavily burden the male population. The higher prevalence of both conditions in the elderly suggests a possible relationship between the two conditions. In addition, in vitro, animal, and human studies have revealed several mechanisms that may relate VDD to ED. The main mechanism by which vitamin D might exert its action on sexual function appears to be through the regulation of endothelial function. Indeed, VDD correlates with several markers of endothelial function. The action of vitamin D on the endothelium would be exercised both indirectly through its intervention in inflammatory processes and through the production of oxygen free radicals, and directly through the regulation of vascular stiffness, the production of nitric oxide, and the regulation of vessel permeability.
  • 343
  • 25 Jun 2023
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