Introduction

Vitamin D (1,25-dihydroxyvitamin D (1,25(OH)2D3)) is a pleotropic steroid with hormone-like activity. It is essential for calcium and bone homeostasis and has been recognized as a significant predictor of bone health. Vitamin D regulates more than 200 human genes in a wide variety of tissues [1]. Vitamin D deficiency continued to be an unrecognized epidemic among many populations with an estimated prevalence of over 1 billion people worldwide [2]. It has been reported in all age groups and genders. Vitamin D deficiency has been correlated with the increased risk of rickets and growth retardation in pediatric population, osteomalacia in adults, and hip fractures in the elderly [3]. Its deficiency has also been implicated in a number of systemic disorders including musculoskeletal system, colorectal cancer, breast cancer, autoimmune (e.g., IBD and IDDM), and cardiovascular diseases [4–8].

The clinical observation suggests that a significant number of Saudi populace has decreased levels of vitamin D in general. The objectives of this study was to determine the prevalence and significance of severe vitamin D deficiency ( 25(OH)D < 25 nmol/l) in Saudi population.

Patients and methods

This is a retrospective observational study to determine the trends and patterns of serum levels of vitamin D among Saudi population, using serum levels of 25-Hydroxy vitamin D [25(OH)D]. Data for 12,625 patients was collected in this study. However, data of 10,709 patients was analyzed. One thousand nine hundred sixteen patients were excluded from the final analysis for various reasons including lack of baseline vitamin D levels, already being on treatment for hypovitaminosis D, and incomplete data. The study population included all patients seen at the Department of Family Medicine and Polyclinic, King Faisal Specialist Hospital and Research Center (KFSH&RC) over 5 years from September 1, 2006 to March 6, 2011. The patients included the employees of the hospitals and their dependents of diverse nationalities and ethnic backgrounds. However, majority of the patients were Saudis from various parts of the kingdom (Table 1).

Table 1 Patient demographics and characteristics
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A baseline vitamin D screening test results encompassing D2, D3, and 25(OH)D levels, were collected for all patients. The data was collected from the hospital electronic medical information system (ICIS). Serum level of 25-hydroxy vitamin D was performed by high-performance liquid chromatography (HPLC) assay at the KFSH&RC Department of Pathology and Laboratory Medicine (DLPM). The study endpoints included determination of the prevalence and severity of vitamin D deficiency and its correlation with age, gender, and country of origin (Table 2). Additional variables included serum parathormone, calcium, phosphate, alkaline phosphatase, albumin levels, eGFR, and bone mineral density. Data was summarized either as percentage or mean ± standard deviation (SD). Vitamin D deficiency was defined as 25(OH)D levels below 75 nmol/l, severe deficiency as levels below 25 nmol/l, and optimum levels as 75–199 nmol/l [5]. The 25(OH)D levels between 50 and 75 nmol/l were considered to be mild deficiency of vitamin D.

Table 2 Patient characteristics stratified by vitamin D severity
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The statistical software SPSS (version 20 by IBM) was used for data analysis. Chi-square is carried out to compare relative distributions, frequency, and severity of hypovitaminosis D in each group stratified by age, gender, and nationality. Patients were substratified into different age groups for comparative analysis with 25(OH)D levels. Data was summarized either as percentage or mean ± standard deviation (SD). The level of significance for inclusion in this model was set at p < 0.05. Descriptive statistics were used to present the basic demographic data. Independent Student’s t test was used to compare the mean values of vitamin D of males and females. Univariate and multivariate logistic regression were used to confirm the association of vitamin D deficiency with age, gender and nationality.

Results

This is the largest community based study in Saudi Arabia. A total of 10,709 patients were enrolled in this comprehensive vitamin D registry over a period of 5 years. Comparison of key explanatory and outcomes variables was done using this large database of detailed clinical information. Population was distributed by gender, age, and nationality. The 25(OH)D levels were stratified into four age groups: children, adolescent, adults, and elderly. The level of vitamin D was determined using the HPLC assay technique and stratified by multiple variables for comparative analysis. A statistically significant difference was found in the mean levels of vitamin D when stratified by gender, using chi-square and independent Student’s t test. The mean levels of 25(OH)D in the overall study population was 44.58 nmol/l (range = 0–714 nmol/l and SD ±34.80 nmol/l). Additional subanalysis indicated that mean serum level of D2 was 17.72 nmol/l and D3 was 31.43 nmol/l. When further stratified by gender, the mean 25(OH)D levels among males was 50.49 nmol/l as compared to 41.88 nmol/l among females.

Substratification by gender, age, and nationality were significant in defining 25(OH)D deficiency, using chi-square and multivariate binary logistic regression analysis. Females had significantly higher prevalence of severe vitamin D deficiency (35.6 % [n = 2,618 of 7,346]) as compared to males (23.7 % [797 of 3,363]; p < 0.000) (Table 2; Fig. 1). When stratified by nationality, the prevalence of severe deficiency of 25(OH)D was significantly higher among Saudi females compared to Saudi males including all age groups (42.6 % [2,055 of 4,828] vs. 27 % [676 of 2,505]; p < 0.000). Only 10.9 % Saudi women had optimum levels of serum vitamin D compared to 18.9 % of men. (Fig. 2).

Fig. 1
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25(OH)D deficiency status by gender

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Fig. 2
figure 2

Levels of 25(OH)D in Saudi population. Severe vitamin D deficiency is more prevalent in Saudi women as compared to men (42.6 vs. 27 %). Only 10.9 % Saudi women have optimum serum levels of vitamin D compared to 18.9 % among men

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Comparative analysis by age group delineated vitamin D deficiency as markedly elevated among adolescents as compared to other age groups (49.2 % [294 of 597] vs. 30.9 % [3,121 of 10,113]; p < 0.000). When stratified by age groups adjusted by nationality, the Saudi adolescents had significantly higher prevalence of severe 25(OH)D deficiency as compared to all other age groups among Saudi population (52.1 % [248 of 476] vs. 36.2 % [2,483 of 6,857]; p < 0.000). Further substratification by gender and nationality indicated that Saudi female adolescents had markedly increased prevalence of vitamin D deficiency compared to their male counterparts (62.7 % [190 of 303] vs. 33.5 % [58 of 173]; p < 0.000) (Table 3; Fig. 3).

Table 3 Difference in vitamin D levels stratified by gender and age in the Saudi population
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Fig. 3
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Difference in vitamin D levels stratified by gender and age in the Saudi population

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When stratified by nationality, the prevalence of severe hypovitaminosis D was significantly higher among Saudis compared to non-Saudis (37.2 % [2,731 of 7,333] vs. 20.3 % [684 of 3,376]; p < 0.000). Severe 25(OH)D deficiency was found to be more prevalent in Saudi adult population as compared to other nationalities (48.3 % [1,947 of 4,028] vs. 21.6 % [563 of 2,602]; p < 0.000). This significant difference was also noticed in other age groups. In non-Saudi population, patients from Middle East region had significantly higher level of severe 25(OH)D deficiency compared to other nationalities (31.9 % [864 of 1,268] vs. 13.3 % [280 of 2,108]; p < 0.000).

Comparative analysis by regional distribution indicated no difference in severe 25(OH)D deficiency levels among the study population, when compared by the cities of Riyadh and Jeddah (33.9 % [3,215 of 9,482] vs. 31 % [326 of 1,053]; p < 0.08).

Discussion

Although Saudi Arabia is one of the sunniest countries, vitamin D deficiency has been prevalent among Saudi population. The kingdom has one of the lowest levels of vitamin D, worldwide, among all age groups, especially adolescent women, children, and elderly. Vitamin D deficiency continues to be prevalent in the kingdom [9, 10] and has also led to increased hospitalizations due to rickets [11, 12].

The prevalence of hypovitaminosis D is significantly higher among Saudi population [13–15]. Saudi women have the highest prevalence of severe vitamin D deficiency compared to men [16, 17]. In our study, 44.6 % of Saudi women were found to have severe vitamin D deficiency as compared to 28.3 % in men. Ardawi et al. [18] reported around 80 % prevalence of hypovitaminosis D among 1,172 Saudi women from the western region of Saudi Arabia, while Sadat-Ali et al. [19] found 28 and 37 % prevalence of hypovitaminosis among male patients 25–35 years and ≥50 years old, respectively. Vitamin D deficiency among Saudi females is prevalent throughout the year, during summer and winter months [20, 21]. A high prevalence of vitamin D deficiency has also been reported among children in Saudi Arabia [22].

Among women, the young adolescent females have the significantly higher risk of severe vitamin D deficiency [9, 23–26]. Consequently, vitamin D deficient adolescents in this phase of growth and development are at increased risk of metabolic bone disorders especially rickets. Since clinical symptoms of Rickets are nonspecific, therefore, it is often underdiagnosed or missed [27]. Maintaining adequate levels of vitamin D during the adolescents age years can improve long-term health outcomes [28].

Several factors have been postulated for the low vitamin D level among Saudi women including dietary habits, lack of sun exposure, traditional clothing [29, 30], dark skin pigmentation, pregnancy, protracted lactation without vitamin D supplementation [31, 32], very hot climate, restricted outdoor activities, obesity, and lack of government regulation for vitamin D fortification of food. Our study found significantly lower levels of serum vitamin D2 as compared to vitamin D3. Vitamin D2 is derived from the food and vitamin D3 from exposure to sun light. Vitamin D contents of the food products in Saudi Arabia are mostly lower than recommended by the United States Code of Federal Regulations. There is none to suboptimal vitamin D fortification of the most commonly consumed foods in Saudi Arabia compared to the USA [33].

Vitamin D deficiency is highly prevalent in Saudi population, in general. However, further subanalysis indicated that adolescent women are the most vulnerable group susceptible to severe vitamin D deficiency in the kingdom. The etiology of this significant finding is multifactorial, in spite of the fact that there is abundance of year-round sunshine. Some of the plausible reasons are sociocultural, lifestyle, and dietary lack of vitamin D fortification and supplementation. A multi-prong approach is warranted to effectively manage this emerging public health threat of epidemic proportions. Education and awareness of the health importance of maintaining optimal circulating 25(OH)D and potential strategies to increase vitamin D intake, early on, is required for primary prevention. Clinicians and educators are encouraged to promote improved vitamin D intake and status, particularly among the high-risk groups like young and adolescent women. Early screening, detection, and intervention can effectively reduce the substantial health care burden in the kingdom by significantly reducing the risk of multiple chronic diseases, such as osteoporosis, cardiovascular disease, diabetes, and some cancers. Loco-regional consensus, comprehensive policies, and guidelines need to be established by the health authorities in conjunction with subject matter experts, health care providers, and scientists. Fortification and supplementation with vitamin D is significantly cost effective as compared to treatment of these chronic diseases. The Ministry of Health and regulatory authorities (SFDA, etc.) need to implement the vitamin D food fortification and develop individual supplementation protocols as per the established international guidelines and standards.

Conclusion

The prevalence of hypovitaminosis D is significantly higher among Saudi population, especially among women. Despite ample sunshine, women are at an inordinate risk of hypovitaminosis D, most likely due to low ultraviolet B radiation exposure, increased skin pigmentation, cultural and lifestyle variations, dietary factors, and lack of supplementation and fortification. Additional longitudinal vitamin D supplementation studies with multiple noncalcemic endpoints are indicated to define the benefits of an optimal vitamin D status in order to establish national consensus guidelines. In addition to culturally sensitive education and awareness, lifestyle modifications, loco-regional screening, and treatment guidelines are needed. Vitamin D screening should be considered early on in children and young women, especially among pregnant or lactating. People at most risk for vitamin D deficiency should be advised to increase their dietary calcium and vitamin D supplements and increased exposure to sunlight. Saudi FDA may have to look into increasing the quantity of vitamin D fortification to reduce highly prevalent vitamin deficiency and reduce significant health care burden as a sequel of hypovitaminosis in the kingdom.