Vitamin D Levels and Prevalence of Vitamin D Deficiency in Turkish Women According to Regions and Age Groups

Introduction

Vitamin D is a hormone essential for calcium and phosphate homeostasis, bone mineralization, and musculoskeletal health [1]. The human body acquires vitamin D primarily through dermal synthesis triggered by ultraviolet B (UVB) radiation exposure and, to a lesser extent, through dietary intake of foods such as oily fish and fortified products [2]. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D, is synthesized in the kidneys following hepatic conversion of vitamin D to 25-hydroxyvitamin D [25(OH)D], the primary circulating form used to assess vitamin D status [3]. Therefore, serum 25(OH)D is considered the best indicator of vitamin D status in clinical and epidemiological studies.

Beyond its established role in bone health, vitamin D deficiency (VDD) is also associated with a wide range of adverse health outcomes, including muscle weakness, osteomalacia, osteoporosis, type 1 and type 2 diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, coronary artery disease, depression, tuberculosis, various types of cancer, and pregnancy-related complications such as preeclampsia, gestational diabetes, increased risk of caesarean delivery, and low birth weight [3–6].

High rates of VDD have been reported even in sunny regions such as South Asia and the Middle East, where cultural clothing, urbanization, indoor lifestyles, and limited dietary sources hinder effective vitamin D synthesis [2,5,7]. Studies have documented VDD prevalences as high as 90.1% in Pakistan, 79.7% in Saudi Arabia, and 95.7% in Jordan [8]. In a longitudinal cohort study in the United Kingdom, 95–96% of South Asian women of childbearing age were found to have year-round VDD, a finding attributed to low UVB exposure due to cultural practices and skin pigmentation [5]. Similarly, despite its favorable latitude, Turkey has consistently reported high rates of VDD, particularly among younger women [9–11].

Globally, the most commonly used classifications for evaluation of vitamin D status are those of the Endocrine Society, the Institute of Medicine (IOM), and the National Health and Nutrition Examination Survey (NHANES) [3,12,13]. Serum 25(OH)D levels below 20 ng/mL are considered deficient, while levels of 20–29 ng/mL indicate insufficiency, and levels ≥30 ng/mL are accepted as sufficient according to the recommendations of the Endocrine Society [3]. Also according to the NHANES, serum 25(OH)D levels of 0–11 ng/mL, 12–19 ng/mL, 20–49 ng/mL, and 50–70 ng/mL are classified as: at risk of vitamin D deficiency, at risk of vitamin D inadequacy, sufficient in vitamin D, and possibly harmful vitamin D levels, respectively [12]. According to the Institute of Medicine (IOM), individuals are considered at risk of vitamin D deficiency when serum 25(OH)D levels are below 12 ng/mL, and at risk of inadequacy when levels are 12–20 ng/mL. A serum 25(OH)D concentration of at least 20 ng/mL is generally considered sufficient. However, levels exceeding 30 ng/mL have not been consistently linked to additional health benefits, and concentrations above 50 ng/mL may raise safety concerns [13].

Although Turkey receives abundant sunlight, multiple studies have paradoxically reported high rates of vitamin D deficiency, especially among women. In a nationwide population-based study by Yeşiltepe-Mutlu et al, widespread deficiency and insufficiency were found among women and younger adults aged 18–35 years, with considerable regional variation [9–11,14–16]. To date, no large-scale study has evaluated vitamin D deficiency stratified by both age and region specifically in women residing in major metropolitan areas of Turkey.

While a limited number of studies have explored regional differences in vitamin D status, most have focused on individual cities or mixed-sex populations. Moreover, no prior research has specifically examined age-related and regional variation in serum 25(OH)D levels among women residing in Turkey’s major metropolitan cities. Therefore, this retrospective study evaluated the association between serum 25(OH)D levels, age, and region in 44 592 women living in Istanbul, Ankara, Antalya, Kayseri, and Diyarbakır between 2011 and 2017.

Material and Methods

ETHICS APPROVAL:

This study was approved by the Ethics Committee of Memorial Hospital (approval no. 2024/13). All data were collected and analyzed in accordance with the ethical standards of the institutional and national research committee, and with the 1964 Helsinki Declaration and its later amendments.

STUDY POPULATION AND DATA COLLECTION:

This retrospective study included 44 592 women aged 18–65 years who resided in and were admitted to hospitals in the cities of İstanbul (Marmara region, latitude 41°N), Ankara (Central Anatolia region, latitude 40°N), Antalya (Mediterranean region, latitude 36.9°N), Kayseri (Central Anatolia region, latitude 38.7°N), and Diyarbakır (Southeast Anatolia region, latitude 37.9°N) between January 2011 and December 2017. The data were obtained from the electronic medical records and laboratory information system of the Memorial Hospital Group, a nationwide, internationally accredited institution in Turkey.

Exclusion criteria included a diagnosis of hyperparathyroidism or hypoparathyroidism, pregnancy, lactation, malignancy, current use of vitamin D supplements, or abnormal liver, renal, or thyroid function tests based on the clinical database.

MEASUREMENT OF SERUM 25-HYDROXYVITAMIN D LEVELS:

Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in a central biochemistry laboratory using a chemiluminescent microparticle immunoassay (CMIA) on the Abbott Architect i2000 system (Abbott Diagnostics, Lake Forest, IL, USA). This method quantitatively detects both 25(OH)D2 and 25(OH)D3 using a delayed one-step competitive immunoassay with flexible assay protocols. The chemiflex technique utilizes microparticles coated with anti-vitamin D IgG antibodies and a biotinylated anti-biotin acridinium-labelled conjugate to form a measurable complex.

Vitamin D status was classified based on the guidelines of the Endocrine Society as follows: deficiency as <20 ng/mL, insufficiency as 20–29 ng/mL, and sufficiency as ≥30 ng/mL [7]. Severe vitamin D deficiency, commonly defined as serum 25(OH)D levels below 10 ng/mL, was based on the threshold of <25 nmol/L traditionally used in Europe to identify the risk of metabolic bone disease [17].

GROUPING AND VARIABLES:

Participants were grouped based on age (18–35, 36–50, and 51–65 years), calendar year (2011–2017), and geographic region (Istanbul, Ankara, Antalya, Kayseri, and Diyarbakır). The primary associations evaluated were between serum 25(OH)D levels and (1) age group, (2) geographic region, and (3) calendar year. These groupings allowed for comparative analysis of vitamin D status across different age ranges, cities, and over time. Vitamin D status categories (severe deficiency, deficiency, insufficiency, and sufficiency) were also compared across these groups.

STATISTICAL ANALYSIS:

All statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics are expressed as mean, standard deviation, median, minimum, maximum, frequency, and percentage. The normality of the data distribution was assessed using the Shapiro-Wilk test, and homogeneity of variances was evaluated using Levene’s test.

Comparative analyses were conducted to evaluate the associations between serum 25(OH)D levels and age groups, geographic regions, and calendar years. For continuous variables such as serum 25(OH)D levels, comparisons between 2 independent groups were performed using the t test for normally distributed data, and the Mann-Whitney U test for non-normally distributed data. For comparisons involving 3 or more groups (eg, age groups or cities), one-way ANOVA or Kruskal-Wallis tests were used, depending on the distribution.

Categorical variables, including vitamin D status categories (severe deficiency, deficiency, insufficiency, sufficiency), were compared across regions and age groups using the chi-square test or Fisher’s exact test, as appropriate. In cases where expected frequencies in contingency tables were less than 20%, the Monte Carlo simulation method was applied. Trends over calendar years were evaluated using appropriate non-parametric tests. A P value of <0.05 or <0.01 was considered statistically significant.

Results

BASELINE CHARACTERISTICS:

The age of participants ranged from 18 to 65 years (mean: 39.5±11.3), and serum 25(OH)D levels ranged from 0.8 to 120.4 ng/mL, with a mean of 20.1±13.7 ng/mL (Table 1). Based on Endocrine Society classifications, 57.7% of participants were vitamin D deficient (<20 ng/mL), 22.4% were insufficient (20–29 ng/mL), and 19.9% had sufficient levels (≥30 ng/mL) (Table 2).

VITAMIN D LEVELS BY AGE GROUP:

When serum 25(OH)D levels were analyzed by age group, VDD prevalence was found to be 59.8% in women aged 18–35 years, 54.6% in the 36–50 age group, and 59.2% in the 51–65 age group. A statistically significant difference was observed between age groups and mean 25(OH)D levels (P<0.05) (Table 3). Post hoc analysis revealed that this difference was primarily due to higher mean vitamin D levels in the 36–50 age group (20.99±13.88 ng/mL) compared to both the 18–35 age group (19.38±12.59 ng/mL) and the 51–65 age group (20.17±15.28 ng/mL) (P<0.001). No significant difference was detected between the 18–35 and 51–65 age groups. These age brackets were selected to represent distinct physiological stages: early reproductive, perimenopausal, and pre-senior age groups.

VITAMIN D LEVELS BY YEAR:

Serum 25(OH)D levels showed fluctuations over the years 2011 to 2017 (Table 4), highlighting the temporal variability of vitamin D status over time. A progressive and statistically significant increase was observed between 2014 (17.72±12.86 ng/mL) and 2017 (22.40±13.91 ng/mL), which may reflect increased public awareness, seasonal effects, or wider supplement use during this period. Seasonal variation in vitamin D synthesis and medication use (such as corticosteroids or anticonvulsants) could also have contributed to the observed fluctuations. Despite this, there were no significant differences between the levels in 2011 and 2017, or between those in 2013 and 2015, suggesting that year-to-year changes were not uniform across the entire period. The annual prevalence of vitamin D deficiency for each year is presented in Table 5.

VITAMIN D LEVELS BY CITY:

The average serum 25(OH)D levels were compared across 5 cities (Table 6). The highest mean level was recorded in İstanbul (22.07±13.56 ng/mL), whereas the lowest was observed in Diyarbakır (14.28±12.35 ng/mL). These differences may be attributed to regional variations in sunlight exposure, lifestyle factors, and access to health services.

OVERALL DISTRIBUTION OF VITAMIN D STATUS:

Across the entire cohort, the distribution of vitamin D status was as follows: severe deficiency (<10 ng/mL) in 25.3% of participants, deficiency (10–19 ng/mL) in 57.7%, insufficiency (20–29 ng/mL) in 22.4%, and sufficiency (≥30 ng/mL) in 19.9%. This distribution reflects the high prevalence of VDD and insufficiency in the cohort, with severe deficiency observed in over one-quarter of participants.

Although the study included a large dataset, it did not capture certain potential confounding factors such as season of blood sampling, dietary patterns, supplementation use, or medications affecting vitamin D metabolism. These limitations may have influenced intergroup differences and temporal trends.

Discussion

This large-scale retrospective study revealed a 57.7% prevalence of vitamin D deficiency among women in 5 major Turkish cities, with significant regional and age-related differences. Mean serum 25(OH)D level was 20.1±13.7 ng/mL. The highest deficiency rate was observed in Diyarbakır, while İstanbul had the highest mean vitamin D level. Women aged 36–50 had significantly higher levels compared to other age groups.

VDD has been reported as a widely prevalent condition affecting global public health, with prevalence rates varying significantly across countries and populations, ranging from 25% in Canada to 36–41% in the United States, 45–52% in New Zealand, and 47–65% in Korea [18]. In a large meta-analysis by Hilger et al, which included data from over 168 000 individuals across 44 countries, the global prevalence of VDD was estimated to be 37.3% [8]. Markedly higher prevalence rates have been observed in the Middle East and South Asia, including 52–64% in Iran, 79.7% in Saudi Arabia, 90.1% in Pakistan, and 95.7% in Jordan [19–22]. Our study found that, similar to the European country’s studies, the prevalence of VDD in Turkish women was 57.7%. However, it is challenging to compare the findings of these studies due to the differences in age, body mass index, latitude, ethnicity, dietary intake of vitamin D, food fortification policies, supplements taken, sun exposure time, skin type, sun protection behavior, seasonal changes, different laboratory techniques, and cut-off levels [18,23].

Latitude is an important factor for endogenous vitamin D production as vitamin D status mainly depends on the production of vitamin D3 in the skin under the influence of sunlight [24]. Latitudes closer to the equator and below 35° latitude are exposed to abundant sunshine [25]. No cutaneous vitamin D production occurs at 51° latitude during some periods of the year, while at 70° latitude vitamin D synthesis can be absent for 5 months [26]. However, VDD is highly prevalent even in the sunniest areas of the world, including Middle East countries, Saudi Arabia, Qatar, United Arab Emirates, India, and Iran (probably because of low exposure to sunlight due to lifestyle and other factors) [27,28]. VDD rates were reported to be 30–90% in the Middle East and North Africa, despite abundant sunlight [29]. Inour study, the cities with the lowest and highest latitude were Antalya and Istanbul respectively, but unexpectedly, VDD prevalence was higher in Antalya (65.7%, mean vitamin D=18.23±13.49 ng/ml) than in Istanbul (50.5%, mean vitamin D=22.07±13.56 ng/ml) (P<0.001). The mean vitamin D serum level was lowest in Diyarbakır (mean vitamin D=14.28±12.35 ng/ml), which has a lower latitude than İstanbul, Ankara, and Kayseri. Turkey, geographically situated between Europe and the Middle East, lies between the 36° and 42°N latitudes and receives abundant sunshine most of the year. Despite this advantage, the prevalence of VDD among women was high (57.7%) in our study, which indicates that measures concerning vitamin D supplementation should be taken as soon as possible.

Among the age groups studied, women aged 36–50 years had significantly higher serum 25(OH)D levels than younger (18–35) and older (51–65) women. There was no significant difference between the younger and older groups. While previous studies suggest a decline in vitamin D with advancing age due to reduced dermal synthesis, our findings indicate that younger women may also be at risk. Potential contributing factors may include limited sun exposure, increased electronic screen time, and dietary patterns low in vitamin D-rich foods, particularly among younger women [25].

Several studies conducted in different regions of Turkey have consistently demonstrated a high prevalence of VDD among women. For example, in Konya, the mean serum vitamin D level was 14.5 ng/mL in a study involving over 28 000 female patients, while in Manisa and İzmir, mean levels were reported as 15.2 ng/mL and 44.6% prevalence in pregnant women, respectively [9,10,14]. Similar patterns were observed in Istanbul (17.3 ng/mL, 66.3% prevalence) and Ankara (54.1% prevalence in elderly women) [15,16]. However, these studies often involved smaller samples or specific subgroups, limiting their generalizability. By including data from 44 592 women across 5 major cities, our study offers a broader representation of vitamin D status in Turkish women.

When compared to the large-scale study by Yeşiltepe-Mutlu et al, our findings show both similarities and notable differences. While the national average reported by Yeşiltepe-Mutlu was 21.0 ng/mL for women, our study found a slightly lower mean of 20.1 ng/mL. At the regional level, discrepancies were more pronounced. For instance, our observed level in Diyarbakır (14.28 ng/mL) was considerably lower than the southeastern Anatolia average of 19.4 ng/mL reported in their study. These differences likely reflect how factors such as urban lifestyle, dietary habits, cultural practices, and socioeconomic conditions vary from city to city, rather than being solely due to differences in laboratory methods [11].

The overall prevalence of VDD and insufficiency in our cohort was 80.1%, highlighting a widespread public health issue among Turkish women. These findings support the consideration of nationwide interventions, including food fortification programs, targeted supplementation strategies, and public awareness campaigns promoting safe sun exposure and vitamin D-rich diets. Special attention should be given to at-risk regions such as southeastern Anatolia, where cultural, economic, and dietary barriers may hinder natural vitamin D synthesis. Region-specific policies that address both behavioral and structural determinants of vitamin D status could play a key role in addressing this widespread public health issue.

One notable finding of our study was that the highest prevalence of VDD was observed in Diyarbakır, despite its location in the sunny southeastern Anatolia region (latitude 37.9°N). Possible contributing factors include lower socioeconomic status, limited seafood consumption due to regional dietary habits, and reduced sun exposure among women related to cultural clothing practices. These findings indicate that geographic sunlight availability alone is not sufficient to ensure adequate vitamin D levels without supportive lifestyle and dietary factors.

Several limitations should be acknowledged in interpreting the findings of this study. Although the sample size of 44 592 women provides strong statistical power, seasonal variations in serum 25(OH)D measurements were not accounted for, which may have influenced the observed levels. Additionally, although patients with documented use of vitamin D supplements were excluded from the study, information on potential confounding factors – such as undocumented supplement use or medications that could affect vitamin D absorption (eg, corticosteroids, anticonvulsants) – was not fully available and therefore not included in the analysis. In addition to the limitations related to study design and data availability, methodological factors related to vitamin D measurement techniques should also be considered. Despite their practical advantages, immunoanalytical techniques, which are often preferred for vitamin D measurement, have some important drawbacks. The limited specificity of the antibodies used in these methods and their susceptibility to interference from various compounds can affect the accuracy of the measurements. In addition, the vitamin D binding protein (DBP) used in some assay systems has different binding affinities for different vitamin D metabolites, which introduces additional variability into the results and can affect the reliability of the measurement.

Conclusions

This large-scale study provides an up-to-date and comprehensive assessment of vitamin D status among women across 5 major Turkish cities over a 6-year period. The findings confirm that VDD is still a widespread issue, with 25.3% of women showing severe deficiency. The differences observed between regions and age groups highlight the need for targeted approaches to reduce this burden. Public health efforts such as raising awareness, promoting supplementation, and evaluating food fortification strategies may help improve vitamin D status and support overall health in this population.