**5. Vitamin D receptor (VDR)**

VDR is a member of the nuclear hormone receptor superfamily and acts as a ligand-inducible transcription factor as well as its non-genomic actions outside of the nucleus [18, 20]. VDRs are present mostly in body organs such as the colon, small intestine, bone, breast, brain, pancreas, pituitary, and muscles [12].

The widespread distribution of VDRs and production of calcitriol may interpret the increasing number of diseases related to vitamin D deficiency [12]. Binding of calcitriol to VDR prompts the transcription of vitamin D-responsive genes (at least 913 genes) involved in cell proliferation, differentiation, function, and the reninangiotensin system [2, 21].

VDR forms a heterodimer complex with the retinoid X receptor (RXR) capable of binding to a vitamin D response element (VDRE) in the promoter region of a target gene and thereby regulates transcription of more than thousand genes [20].

#### **6. Factors affecting vitamin D synthesis**

Many factors affect vitamin D synthesis and its concentration [1, 3, 6, 11, 17, 19, 20]: aging (age decreases the capacity of the skin to produce vitamin D due to lower availability of 7-DHC), season of the year (autumn and winter), weather conditions (cloudiness), geographical locations (higher latitude), sun exposure, sunscreen (with a protection factor of 30 reduces above 95% of vitamin D synthesis in the skin), skin pigmentation (darker skin needs 3–5 times longer sun exposure to synthesize the same amount of vitamin D than light skin since melanin absorbs UVB radiation), genetic factors (SNPs and mutations), skin damage (burns decrease its production), adiposity (obesity has reduced vitamin D levels), workplace (indoor vs. outdoor), lifestyle, physical activity, clothing habits, air pollution, smoking, diet and calcium intake, vitamin D supplements, and individual height.

#### **7. Vitamin D status**

Vitamin D status is best determined by measuring serum 25-hydroxyvitamin D [25(OH)D]; a level higher than 50 nmol/L (30 ng/mL) contributes to the optimal calcium absorption, fall prevention, and prevention of the fracture [4, 22]. Below

**7**

mortality [10].

*Vitamin D and Its Deficiency in Saudi Arabia DOI: http://dx.doi.org/10.5772/intechopen.88745*

specific and cheap testing method [4].

**8. Vitamin D deficiency**

this level, PTH levels increase blood circulation, causing secondary hyperparathyroidism, and increase the risk of osteoporosis and fractures leading to bone loss. In addition, moderate increase of PTH may also enhance insulin resistance, weight gain, hypertension, left ventricular hypertrophy, and acute phase response, increas-

According to the Committee of the Institute of Medicine (IOM, USA) and the Endocrine Society [19, 23], vitamin D status defined the values lower than 50 nmol/L (20 ng/mL) as vitamin D deficiency (VDD), while values between 50 and 75 nmol/L are indicated to vitamin D insufficiency (VDI), and values equal or above 75 nmol/L (30 ng/mL) is described as adequate or sufficient vitamin D. The

Serum [25(OH)D] test is detected by using high-performance liquid chromatography/mass-spectrometry (LC/MS) methodology [4, 19] which is recommended by the National Diet and Nutrition Survey [19]. The high cost for vitamin D detection hampers the diagnosis of vitamin D deficiency. There is a great need to develop a

Most studies have identified the vitamin D insufficiency (VDI) at concentrations of [25(OH)D] less than 75 nmol/L (30 ng/mL) and vitamin D deficiency

Vitamin D deficiency is still a highly prevalent disorder. It is estimated that ~1 billion people are deficient or have insufficient levels of vitamin, in spite of foods

VDD is widespread in the whole world as well as predominant in Asia and in the Middle East (more than 50% of the population is VDD and about 75% is VDI) [4]. VDD is found in 30–50% of otherwise healthy middle-aged to elderly adults [11]. Deficiency of vitamin D can result from many reasons such as dietary inadequacy of vitamin D, poor absorption and use, increased requirement, increased excretion and catabolism, limited sunlight exposure, and inefficient production in the skin. Dietary deficiency of vitamin D is associated with milk allergy, lactose intolerance, ovo-vegetarianism, and veganism [1, 4]. In addition, various diseases affect the bioavailability of vitamin D, such as gastrointestinal disorders which limit its absorption; kidney and liver diseases can prevent the activation of the parenteral vitamin D or impair the conversion of vitamin D into its active metabolites [4]. Severe VDD in adults leads to osteomalacia while in children leads to rickets, defective bone mineralization, increased bone turnover, increased risk of fractures [4], impaired reproductive function, and production of gonadal hormone that may affect other organs, e.g., gastrointestinal and renal calcium handling, renal

In the critical care condition, VDD has been associated with adverse outcomes

A total of 132 articles studying the deficiency of vitamin D in Saudi Arabia were identified based on the initial PubMed search criteria. About 20 studies have investigated the vitamin D deficiency in healthy individuals living in Saudi Arabia during

such as infections, longer length of stay, acute kidney injury, and higher

(VDD) at concentrations below 50 nmol/L (20 ng/mL) [1, 4, 10, 17].

fortified with vitamin D and wide supplement intake [2].

CYP27B1 activity, and bone function [20].

**9. Vitamin D deficiency in Saudi Arabia**

ing the risk of ischemic arrhythmias and cardiovascular mortality [4].

IOM adds extra criterion which is severe VDD with 25 nmol/L (10 ng/mL).

*Vitamin D and Its Deficiency in Saudi Arabia DOI: http://dx.doi.org/10.5772/intechopen.88745*

*Vitamin D Deficiency*

VDR [20].

half-life of about 15 days [2].

**5. Vitamin D receptor (VDR)**

angiotensin system [2, 21].

and individual height.

**7. Vitamin D status**

**6. Factors affecting vitamin D synthesis**

[25(OH)D] is an inactive and the most abundant circulating form of vitamin D, and it is generally measured when assessing vitamin D status which has a circulating

Thirdly, 1,25-dihydroxyvitamin D [1,25(OH)2D], the biologically active form of vitamin D, is generated through second hydroxylation that takes place in the kidney [6] by the enzyme cytochrome P-450 (CYP27B1) monooxygenase 25(OH)D-1-αhydroxylase [13] [1,25(OH)2D], which serves as a hormone to regulate a variety of cellular functions in other organs or acts inside the kidneys in an autocrine and/or paracrine fashion [5]. Several factors regulate the levels of [1,25(OH)2D], 25(OH) D-1-α-hydroxylase (whose hydroxylation is activated by PTH), calcitonin (which is inhibited by serum levels of calcium), phosphorus, and [1,25(OH)2D] itself [19]. Finally, [1,25(OH)2D] enters the cell by diffusion and binds and activates the

VDR is a member of the nuclear hormone receptor superfamily and acts as a ligand-inducible transcription factor as well as its non-genomic actions outside of the nucleus [18, 20]. VDRs are present mostly in body organs such as the colon, small intestine, bone, breast, brain, pancreas, pituitary, and muscles [12].

The widespread distribution of VDRs and production of calcitriol may interpret the increasing number of diseases related to vitamin D deficiency [12]. Binding of calcitriol to VDR prompts the transcription of vitamin D-responsive genes (at least 913 genes) involved in cell proliferation, differentiation, function, and the renin-

VDR forms a heterodimer complex with the retinoid X receptor (RXR) capable of binding to a vitamin D response element (VDRE) in the promoter region of a target gene and thereby regulates transcription of more than thousand genes [20].

Many factors affect vitamin D synthesis and its concentration [1, 3, 6, 11, 17, 19, 20]: aging (age decreases the capacity of the skin to produce vitamin D due to lower availability of 7-DHC), season of the year (autumn and winter), weather conditions (cloudiness), geographical locations (higher latitude), sun exposure, sunscreen (with a protection factor of 30 reduces above 95% of vitamin D synthesis in the skin), skin pigmentation (darker skin needs 3–5 times longer sun exposure to synthesize the same amount of vitamin D than light skin since melanin absorbs UVB radiation), genetic factors (SNPs and mutations), skin damage (burns decrease its production), adiposity (obesity has reduced vitamin D levels), workplace (indoor vs. outdoor), lifestyle, physical activity, clothing habits, air pollution, smoking, diet and calcium intake, vitamin D supplements,

Vitamin D status is best determined by measuring serum 25-hydroxyvitamin D [25(OH)D]; a level higher than 50 nmol/L (30 ng/mL) contributes to the optimal calcium absorption, fall prevention, and prevention of the fracture [4, 22]. Below

**6**

this level, PTH levels increase blood circulation, causing secondary hyperparathyroidism, and increase the risk of osteoporosis and fractures leading to bone loss. In addition, moderate increase of PTH may also enhance insulin resistance, weight gain, hypertension, left ventricular hypertrophy, and acute phase response, increasing the risk of ischemic arrhythmias and cardiovascular mortality [4].

According to the Committee of the Institute of Medicine (IOM, USA) and the Endocrine Society [19, 23], vitamin D status defined the values lower than 50 nmol/L (20 ng/mL) as vitamin D deficiency (VDD), while values between 50 and 75 nmol/L are indicated to vitamin D insufficiency (VDI), and values equal or above 75 nmol/L (30 ng/mL) is described as adequate or sufficient vitamin D. The IOM adds extra criterion which is severe VDD with 25 nmol/L (10 ng/mL).

Serum [25(OH)D] test is detected by using high-performance liquid chromatography/mass-spectrometry (LC/MS) methodology [4, 19] which is recommended by the National Diet and Nutrition Survey [19]. The high cost for vitamin D detection hampers the diagnosis of vitamin D deficiency. There is a great need to develop a specific and cheap testing method [4].
