Abstract

The pleiotropic effects of vitamin D on the various metabolic, anticancer, and immunomodulatory functions of the body based on the presence of vitamin D receptors (VDR) on various cell types has been recognized worldwide now. Of few understood mechanisms of immunomodulatory actions of vitamin D are the suppressive action on the maturation of antigen-presenting cells and decrease in the levels of pro-inflammatory cytokines. Vitamin D deficiency has been implicated in the immune diseases like rheumatic diseases, asthma, psoriasis, and multiple sclerosis. Vitamin D deficiency has been associated with increased frequency and severity of disease flares in rheumatic diseases like lupus and rheumatoid arthritis. Other studies have shown higher prevalence of persistence and evolution in to more definite rheumatic disorder in undifferentiated arthritis and undifferentiated connective tissue disorder patients with vitamin D deficiency. Multiple factors like avoidance of sunlight, the use of corticosteroids and hydroxychloroquine, skin pigmentation, etc. should be considered when evaluating vitamin D levels in these patients, needless to say the consideration of higher-dose supplement for these patients. It is thus prudent that all patients with established or undifferentiated rheumatic diseases are evaluated for vitamin D status and an adequate supplementation is recommended to prevent the associated consequences.

Keywords: vitamin D, vitamin D deficiency, immunomodulation, rheumatic diseases, inflammation

### 1. Introduction

Vitamin D has two bioequivalent forms, D2 (ergocalciferol) and D3 (cholecalciferol). It is synthesized mainly from 7-dehydrocholesterol in keratinocytes of the skin stimulated by UVB of sunlight and metabolized in the liver to 25(OH)D and subsequently converted to its active form 1,25(OH)2D in the kidney [1, 2]. It maintains calcium and phosphorus homeostasis, optimizes bone health and muscle function and immunomodulation, has antiproliferative effect on keratinocytes, and suppresses cytokine production [3, 4]. Serum 25(OH)D3 level of at least 50 nmol/l is considered to be optimal for bone health and extra skeletal effects [5]. The term hypovitaminosis D includes vitamin D insufficiency and deficiency. Vitamin D insufficiency is defined as a serum 25(OH)D concentration of 21– 29 ng/ml (50–75 nmol/L), whereas deficiency means serum 25(OH)D level of <20 ng/ml (<50 nmol/L) [6].

Vitamin D is also known as the sunshine vitamin. The importance of sunlight for human health came into light with the industrial revolution in Northern Europe [7]. Sniadecki first published an article in 1822 about high prevalence of rickets in children who lived in the inner city in comparison to those who lived in the rural areas [8]. Many observations regarding the sun exposure and rickets have been published in the course of time. Studies have also revealed the high prevalence of vitamin D deficiency in general population, mostly owing to lack of sun exposure.

bed radiation is effective in increasing blood concentrations of vitamin D3 and 25-hydroxyvitamin D3 [25(OH)D3]. One minimal erythemal dose (MED) is equivalent to 10–50 times the recommended intakes [3]. Oily fishlike salmon, mackerel, sardines, and cod liver oil are also considered good sources of vitamin D [13].

There are numerous causes of vitamin D deficiency. Decreased synthesis from the skin is one of the main causes. Less exposure to sunlight, lifestyle, skin pigmentation, abundant use of sunscreen lotion, and geographical variation owe to less dermal synthesis. Decreased bioavailability due to malabsorption, decreased synthesis of active form of vitamin D due to liver or renal failure, or increased catabolism with the use of various medications like glucocorticoids and anticonvulsants also cause deficiency. VDD is also seen in diseases like rickets, osteomalacia, hyper-

The daily recommended allowance of vitamin D is 400–600 IU in children and

homeostasis and optimizes bone health and muscle function [4]. Adequate vitamin D is necessary to prevent rickets and osteomalacia [3]. Though still controversial, it is reported that calcium and vitamin D supplementation prevents fall risk and also decreases the osteoporotic fracture in older adults [15]. Vitamin D supplementation of 700–800 IU per day reduces falls and

2.PTH and vitamin D: There is an inverse relationship between circulating 25

relationship between vitamin D and muscle function. Though improvement of muscle strength with supplementation of vitamin D has been observed in few

4. Skin and vitamin D: 1,25(OH)2D analogs calcipotriol and maxacalcitol can be used for the treatment of the hyperproliferative skin diseases like psoriasis

5.Cancer and vitamin D: Vitamin D deficiency has been associated with cancers, especially colorectal [21, 22]. Calcium and 1,25(OH)2D3 participate in the regulation of keratinocyte proliferation and differentiation and may prevent the development of skin cancer [20]. Observational studies have shown the relationship between vitamin D deficiency and carcinoma of the breast, colon,

3.Muscle function and vitamin D: There are several studies that suggest a

trials [17, 18], the causal relation has not been established yet.

(OH)D levels and parathyroid hormone (PTH) [1].

[3, 19] and non-melanoma skin cancer [20].

and thyroid [3], but the results are not consistent.

1.Bone and vitamin D: Vitamin D maintains calcium and phosphorus

4. Causes of vitamin D deficiency

DOI: http://dx.doi.org/10.5772/intechopen.88677

parathyroidism, and granulomatous disorders [14].

Vitamin D in Rheumatic Diseases: Interpretation and Significance

5. Daily recommended dose of vitamin D

adults and 800 IU in adults >70 years [9].

fractures in older adults [16].

6. Clinical applications

85

### 2. Vitamin D structure, synthesis, and metabolism

Vitamin D is a fat-soluble seco-steroid made from four cholesterol rings IOM (Institute of Medicine) [9]. It has two bioequivalent forms, D2 (ergocalciferol) and D3 (cholecalciferol). Vitamin D2 is derived from the plant sterol ergosterol [1, 9]. Vitamin D from the diet or dermal synthesis is biologically inactive [10]. Vitamin D3 is synthesized mainly from 7-dehydrocholesterol in keratinocytes of the skin stimulated by UVB of sunlight [3]. Under the influence of sunlight (ultraviolet radiation, action spectrum 280–320 nM, or UVB), 7-dehydrocholesterol in the epidermis is converted to vitamin D (Figure 1). Keratinocytes express the vitamin D receptor (VDR) due to which they are capable of responding to the 1,25(OH)2D produced [11]. Both UVB intensity and skin pigmentation level contribute to the rate of D3 formation [12]. D3 is converted to 25(OH)D (calcidiol) in the liver by a number of enzymes. 25-Hydroxyvitamins D2 and D3 produced by the liver enter the circulation and the kidney bound to vitamin D-binding protein. The kidney metabolizes 25(OH)D to the active metabolite 1,25(OH)2D3.

Figure 1.

Overview of vitamin D, UpToDate 2019.
