Abstract
Objective
This study aims to investigate the prevalence of serum vitamin D deficiency in the Xining, Qinghai Province (elevation 2260 m, oxygen partial pressure 16.10 kPa, 36°13’–37°28’N) and to explore the correlation between 25-hydroxyvitamin D [25(OH)D] levels and inflammatory markers.
Methods
A total of 2,080 subjects were enrolled, serum 25(OH)D, and inflammatory markers—including procalcitonin (PCT), interleukin 6 (IL-6), and C reactive protein (CRP) —were measured. According to serum 25(OH)D concentrations, participants were divided into three groups: vitamin D sufficiency (> 30 ng/mL), insufficiency (20–30 ng/mL), and deficiency (< 20 ng/mL). Spearman correlation analysis, partial correlation analysis and Logistic regression analysis were performed.
Results
The mean 25(OH)D concentration was 13.99 ± 7.20 ng/mL, with the proportions of vitamin D deficiency, insufficiency and sufficiency being 83.65%, 13.65% and 2.70%, respectively. The levels of PCT, IL-6 and CRP in the deficiency group were significantly higher than those in the other two groups (P < 0.05). The vitamin D deficiency was higher in females than in males (87.95% vs. 77.47%, P < 0.05). The 25(OH)D level peaked in summer and reached the lowest level in winter (P < 0.05), while no significant intergroup difference was observed across different age groups. PCT, IL-6 and CRP were significantly negatively correlated with 25(OH)D (r=-0.674, -0.533, -0.292, P < 0.01), and these correlations remained significant after adjustment for confounding factors (P < 0.01). Logistic regression analysis revealed that female gender (OR = 4.043), PCT (OR = 2491.808), IL-6 (OR = 1.903) and CRP (OR = 1.608) were independent risk factors for vitamin D deficiency (P < 0.01).
Conclusion
Residents in high-altitude Xining suffer from severe vitamin D deficiency correlated with heightened inflammation. Female sex and elevated inflammatory biomarkers independently increase deficiency risk, and seasonal sunlight regulates 25(OH)D levels. Gender- and season-specific vitamin D supplementation could mitigate inflammatory load in highland residents.
Keywords: Vitamin D, 25(OH)D, High altitude, Hypoxia, Deficiency, Inflammatory markers
Introduction
Vitamin D is an essential fat-soluble vitamin that plays a pivotal role in regulating calcium and phosphorus metabolism, maintaining bone health, and modulating immune function [1–3]. Vitamin D deficiency (VDD) has become a global public health concern, affecting populations across different age groups, regions, and ethnicities, with prevalence varying significantly due to geographical, environmental, dietary, and lifestyle factors [4–8].
The plateau is characterized by harsh environmental conditions, such as hypoxia, strong ultraviolet radiation, low temperatures, and a limited variety of food [9]. These factors collectively pose potential challenges to the nutritional status and physiological homeostasis of residents and long-term inhabitants in these regions [9, 10]. Ultraviolet B (UVB) radiation is the primary source of endogenous vitamin D synthesis in the human body, as it triggers the conversion of 7-dehydrocholesterol in the skin to pre-vitamin D₃, which is further isomerized to the active form of vitamin D [11]. However, despite the high UVB radiation levels in high-altitude areas, several confounding factors may counteract its beneficial effect on vitamin D synthesis—including prolonged indoor stay due to harsh weather, heavy clothing coverage to protect against cold and UV damage, and potential changes in skin pigmentation among long-term high-altitude dwellers, which may reduce UV penetration [12]. Low oxygen tension is a core feature of high-altitude environments. Research have shown that hypoxia can modulate inflammatory responses [13]. Individuals living at high altitudes present elevated pro-inflammatory cytokines (e.g., tumor necrosis factor-α TNF-α, interleukin-6 IL-6, C-reactive protein CRP), which may be associated with cellular stress and immune system activation triggered by tissue hypoxia [14–17]. Both vitamin D deficiency and high-altitude hypoxia can independently trigger inflammatory disorders. Therefore, it is reasonable to hypothesize that the two factors may exert a synergistic effect among people living at high altitudes, further elevating the risk of chronic diseases.
To date, there is a lack of systematic research on the correlation between vitamin D deficiency and inflammatory markers in high-altitude populations, and the internal mechanism by which high-altitude hypoxia affects this correlation remains unclear. This study selected the widely recognized standardized inflammatory markers IL-6, CRP, and procalcitonin (PCT) to conduct a correlation analysis with vitamin D levels. As a key pro-inflammatory factor in the early stages of the inflammatory response, IL-6 can induce the production of acute-phase proteins such as CRP, and its levels can objectively reflect the severity of inflammation and the body’s inflammatory activation status; CRP testing is convenient, stable and widely used; its rise occurs later than that of IL-6 and persists for a longer duration, making the two markers highly complementary. Furthermore, CRP provides a good indicator of non-infectious inflammation, such as aseptic and autoimmune inflammation; PCT, on the other hand, is highly infection-specific, with extremely low levels in healthy individuals, rising significantly only in cases of severe bacterial infection or sepsis. The combined use of these three markers provides comprehensive coverage of the entire process of inflammation—from onset and progression to resolution—and facilitates the assessment of non-specific inflammation, bacterial infections and systemic inflammatory responses.
Given the growing population residing in or migrating to high-altitude areas for work, residence, or tourism, clarifying the prevalence of VDD and its association with inflammatory markers in this unique population is of great public health and clinical significance. It can provide evidence-based support for the development of targeted vitamin D supplementation strategies and inflammatory disease prevention measures for high-altitude dwellers. Therefore, this study aims to investigate the prevalence of VDD in high-altitude, hypoxic areas, and to explore its correlation with key inflammatory markers, thereby filling the research gap in this field and providing new insights into the nutritional and inflammatory health management of high-altitude populations.
Methods
Study population
This study adopted consecutive sampling method, enrolled all healthy subjects who underwent 25-hydroxyvitamin D [25(OH)D] testing during routine annual physical examinations at the Health Screening Center of Qinghai Provincial People’s Hospital from January 2022 to December 2024. Exclusion Criteria: (1) Chronic wasting diseases; intestinal malabsorption syndrome; patients with severe hepatic impairment; estimated glomerular filtration rate (eGFR) < 60 mL/min; (2) Use within the past year of medications affecting bone metabolism, including glucocorticoids, anticonvulsants, anticoagulants, calcitonin, vitamin D preparations, vitamin D analogues, bisphosphonates, etc.; (3) History of fractures, bone metastases from tumors, or malignant tumors such as prostate cancer; (4) Pregnant women, hypertension, diabetes or a BMI ≥ 28; (5) Participants with incomplete key indicators such as 25(OH)D and PCT.
The center serves residents from surrounding villages and towns, including individual attendees, community groups and institutional staff. The geographic and environmental parameters of Xining are as follows: longitude 100°52′–101°54′ E, latitude 36°13′–37°28′ N, altitude 2,260 m, atmospheric pressure 77.35 kPa, partial pressure of oxygen 16.10 kPa, annual mean temperature 5.5 °C, and annual average ultraviolet irradiance 250–300 W/m².
Data collection procedures
All subjects underwent standardized medical history interviews conducted by dedicated personnel, and fasting venous blood samples (after an 8-hour fast) were collected, along with uniform measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), uric acid (UA), serum creatinine (CRE), glucose (GLU), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum calcium (Ca), serum phosphorus (P), serum magnesium (Mg). C-reactive protein (CRP) was measured using an automatic biochemical analyzer (AU5831, Beckman Coulter, United). Interleukin-6 (IL-6) and procalcitonin (PCT) levels were measured using a Roche Cobas e 602 automatic chemiluminescence immunoassay analyzer.
Serum 25(OH)D was measured using chemiluminescence (Roche Modular E170 fully automated immunoassay analyzer, Switzerland, measurement range from 3 to 400 ng/ml), sensitivity and specificity were 95% and 99%, respectively). The inter- and intra-assay coefficients of variation for the 25(OH)D measurements were 5.5% and 4.4%. This laboratory’s 25(OH)D testing has undergone comprehensive methodological validation. We regularly participate in national proficiency testing and interlaboratory quality assessment schemes, adhere to national standards and aligns its QC system with DEQAS, and implement dual internal and external quality control measures. We use a standardized testing platform, reagents and calibrators, and establish high, medium and low concentration internal quality controls. Samples are tested in batches according to enrolment date to avoid confounding seasonal effects with testing batches; Proficiency testing results remain stable throughout the year, with complete instrument maintenance and reagent stability records. There is no detection drift or methodological bias, ensuring that seasonal fluctuations accurately reflect natural variations in population indicators.
Assessment of Vitamin D nutritional status
25(OH)D) is the primary form of vitamin D found in the human body. It is stable (with a half-life of 2 weeks), and its levels accurately reflect the total amount of vitamin D obtained from dietary intake and endogenous synthesis; it is therefore widely recognized as the optimal biomarker for assessing vitamin D nutritional status in humans [1, 4]. Accordingly, serum 25(OH)D was selected as the indicator to reflect vitamin D status in the present study, serum 25(OH)D grouping criteria follow the “Clinical Application Consensus on Vitamin D and Its Analogues” published by the Chinese Medical Association’s Osteoporosis and Bone Mineral Diseases Branch in February 2025: serum 25(OH)D > 30 ng/mL indicates adequate vitamin D status, 20–30 ng/mL indicates suboptimal vitamin D status, < 20 ng/mL indicates VDD [18].
Statistical methods
Statistical analysis was performed using SPSS 25.0 software. Quantitative data that follow a normal distribution are expressed as the mean ± standard deviation, comparisons among multiple groups were conducted using one-way analysis of variance (ANOVA), followed by pairwise post-hoc tests (LSD-t test). Qualitative data are expressed as number (percentage) and were compared between groups using the chi-square (χ²) test. Quantitative data from non-normal distributions were described using the median (interquartile range), with comparisons between two groups performed using the Wilcoxon rank-sum test and comparisons among multiple groups using the Kruskal-Wallis H rank-sum test. Spearman’s rank correlation analysis was used to assess the crude correlation between vitamin D levels and inflammatory indicators. Subsequently, partial Pearson correlation analysis was performed to evaluate their independent correlation while adjusting for confounding factors including age, gender, height, weight, BMI, current smoking, current alcohol drinking, and season. Analyze the risk factors for vitamin D deficiency using the binary logistic regression model. A significance level of α = 0.05 was adopted, with P < 0.05 considered statistically significant.
Results
Clinical characteristics
A total of 2,080 subjects were enrolled, with an average 25(OH)D level of 13.99 ng/mL. The highest recorded 25(OH)D level was 66.70 ng/mL, while the lowest was < 3 ng/mL. The proportions of subjects with VDD, insufficiency, and sufficiency were 83.65%, 13.65%, and 2.89%, respectively (Table 1).
Table 1.
Baseline characteristics
| Characteristics | Data |
|---|---|
| Age (mean ± SD. years) | 48.80 ± 13.82 |
| Sex, female [n (%)] | 1228 (59.04) |
| 25(OH)D (mean ± SD, ng/mL) | 13.99 ± 7.20 |
| Deficient [n (%)] | 1740 (83.65) |
| Insufficiency [n (%)] | 284 (13.65) |
| sufficiency [n (%)] | 56 (2.70) |
| PCT (mean ± SD, ng/mL) | 0.59 ± 0.22 |
| IL-6 (mean ± SD. pg/mL) | 15.68 ± 5.11 |
| CRP (mean ± SD, mg/L) | 7.30 ± 1.67 |
n = 2080
Abbreviations: CRP C reactive protein, IL-6 Interleukin-6 and PCT Procalcitonin
Biological indicators differences
There were no significant differences in biological indicators such as ALT, AST, and BUN among the three groups (P > 0.05, Table 2).
Table 2.
Biological Indicators Difference in different groups
| Groups | Deficient (n = 1740) |
Insufficient (n = 284) |
Sufficient (n = 56) |
P |
|---|---|---|---|---|
| Age (years) | 49.38 ± 13.87 | 49.93 ± 13.47 | 51.05 ± 14.00 | 0.365 |
| ALT (U/L) | 31.60 ± 26.31 | 35.34 ± 31.05 | 35.19 ± 25.50 | 0.224 |
| AST (U/L) | 24.36 ± 13.52 | 26.34 ± 23.55 | 24.97 ± 11.64 | 0.197 |
| BUN (mmol/L) | 5.42 ± 1.54 | 5.75 ± 1.37 | 5.63 ± 2.30 | 0.062 |
| UA (umol/L) | 321.33 ± 105.96 | 335.91 ± 100.43 | 336.78 ± 99.84 | 0.830 |
| CRE (µmol/L) | 77.41 ± 14.18 | 86.56 ± 11.86 | 90.00 ± 16.05 | 0.107 |
| GLU (mmol/L) | 4.90 ± 1.33 | 4.93 ± 1.42 | 5.23 ± 2.14 | 0.059 |
| HbA1c (%) | 5.97 ± 0.94 | 6.00 ± 0.97 | 6.09 ± 1.32 | 0.525 |
| TC (mmol/L) | 4.67 ± 0.97 | 4.70 ± 0.94 | 5.13 ± 1.13 | 0.393 |
| TG (mmol/L) | 1.40 ± 1.33 | 1.32 ± 0.89 | 1.59 ± 1.21 | 0.633 |
| HDL-C (mmol/L) | 1.28 ± 0.29 | 1.25 ± 0.25 | 1.30 ± 0.27 | 0.252 |
| LDL-C (mmol/L) | 3.02 ± 0.84 | 3.12 ± 0.79 | 3.35 ± 0.98 | 0.445 |
| Ca (mmol/L) | 2.20 ± 0.15 | 2.22 ± 0.13 | 2.20 ± 0.13 | 0.873 |
| P (mmol/L) | 0.98 ± 0.22 | 1.04 ± 0.20 | 0.99 ± 0.24 | 0.823 |
| Mg (mmol/L) | 0.81 ± 0.10 | 0.79 ± 0.11 | 0.84 ± 0.10 | 0.762 |
Values are given as mean ± SD
Abbreviations: ALT Alanine aminotransferase, AST Aspartate aminotransferase, BUN Blood urea nitrogen, UA Uric acid, CRE Serum creatinine, GLU Glucose, glycated hemoglobin, HbA1c glycated hemoglobin, TC Total cholesterol, TG Triglycerides, HDL-C High-density lipoprotein cholesterol, LDL-C Low-density lipoprotein cholesterol, Ca serum calcium, P serum phosphorus, Mg serum magnesium
Significant differences in PCT, IL, and CRP levels were observed among the deficient, insufficient, and sufficient groups, exhibiting a progressively decreasing trend (P < 0.05, Table 3).
Table 3.
25(OH)D and inflammatory markers Difference in different groups
| Groups | Deficient (n = 1740) |
Insufficient (n = 284) |
Sufficient (n = 56) |
|---|---|---|---|
| 25(OH)D (ng/mL) * | 11.56 (8.11, 15.05) c | 23.00 (21.20, 25.14) b | 35.45 (32.75, 42.34) a |
| PCT (ng/mL) # | 1.33 ± 0.28 a | 0.17 ± 0.05 b | 0.07 ± 0.02 c |
| IL-6 (pg/mL) # | 15.65 ± 1.92 a | 13.99 ± 1.05 b | 7.75 ± 1.93 c |
| CRP (mg/L) # | 7.69 ± 2.01 a | 6.04 ± 1.89 b | 4.54 ± 1.54 c |
* M (P25, P75); # mean ± SD. In each row, distinct superscript letters represent statistically significant differences in pairwise comparisons (P < 0.05)
Abbreviations: PCT Procalcitonin, IL-6 Interleukin-6, and CRP C reactive protein
Compare 25(OH)D levels across different ages and genders
Among different age groups, there were no statistically significant differences in serum 25(OH)D levels. There were no statistically significant differences in the prevalence of vitamin D deficiency, and insufficiency + sufficiency across the various age groups (P > 0.05, Table 4).
Table 4.
25(OH)D levels in different age groups
| Age, years | n | 25(OH)D (ng/mL) * | Deficient# | Insufficient+ Sufficient # |
|---|---|---|---|---|
| 18–45 (young adults) | 290 | 12.43 (9.28, 16.95) | 248 (85.52) a | 42 (14.48) b |
| 46–60 (middle-aged subjects) | 782 | 13.09 (8.99, 18.30) | 632 (80.82) a | 150 (19.18) a |
| 61–75 (elderly subjects) | 656 | 12.70 (8.16, 17.13) | 558 (85.06) b | 98 (14.94) b |
| >75 (subjects of advanced age) | 352 | 12.47 (8.85 ,17.33) | 302 (85.80) a | 50 (14.21) b |
* M (P25, P75), χ2 2.323, P 0.508; # [n (%)], χ2 9.951, P 0.019, in the same column, distinct superscript letters mean significant pairwise differences (P < 0.05)
Among different genders, males exhibited higher serum 25(OH)D levels than females (P < 0.05). The VDD rate was higher in the female population than in the male population, with statistically significant differences (P < 0.05, Table 5).
Table 5.
25(OH)D levels in different sexes
| Sexes | n | 25(OH)D (ng/mL) * | Deficient # | Insufficient+ Sufficient # |
|---|---|---|---|---|
| Male | 852 | 14.75 (10.90, 19.32) | 660 (77.47) | 192 (22.53) |
| Female | 1228 | 11.35 (7.89, 16.23) | 1080 (87.95) | 148 (12.05) |
* M (P25, P75), Z -7.507, P 0.000; # [n (%)], χ2 40.425, P 0.000
25(OH)D levels across different seasons
Serum 25(OH)D levels exhibited statistically significant differences across seasons (P < 0.05). Pairwise comparisons revealed no statistically significant difference between winter and spring (P > 0.05), while all other pairwise comparisons showed statistically significant differences (P < 0.05). 25(OH)D levels were highest in summer, followed by autumn, and lowest in winter (Fig. 1).
Fig. 1.
25(OH)D levels in different seasons. Note: In the current study, seasonal grouping was predefined: spring comprises December, January and February; summer comprises March, April and May; autumn comprises June, July and August; winter comprises September, October and November
Analysis of correlation between inflammatory factors and 25(OH)D
Spearman correlation analysis showed that the levels of PCT, IL-6, and CRP were negatively correlated with the 25(OH)D (Table 6, P < 0.05). After adjusting for confounding factors including age, gender, height, weight, current smoking status, current alcohol drinking status, and season, the results of partial correlation analysis revealed that 25(OH)D was negatively correlated with PCT, IL and CRP (Table 6, P < 0.01).
Table 6.
Correlation analysis between inflammatory factors and 25(OH)D
| Indicators | Unadjusted rs | P | Adjusted r | P |
|---|---|---|---|---|
| PCT (ng/mL) | –0.674 | 0.000** | –0.513 | 0.000** |
| IL-6 (pg/mL) | –0.533 | 0.000** | –0.380 | 0.000** |
| CRP (mg/mL) | –0.292 | 0.000** | –0.264 | 0.000** |
**P < 0.01
Abbreviations: CRP C reactive protein, IL-6 Interleukin-6, and PCT Procalcitonin
Logistic regression analysis of factors influencing vitamin D deficiency
Binary logistic regression analysis was used to screen the risk factors for vitamin D deficiency, and the results showed that Gender, PCT, IL-6, and CRP were risk factors for vitamin D deficiency (Table 7).
Table 7.
Logistic regression analysis of factors influencing vitamin D deficiency
| Indicators | B | S.E. | Wald | OR (95%CI) | P |
|---|---|---|---|---|---|
| Age | 0.007 | 0.011 | 0.335 | 1.007 (0.985–1.029) | 0.551 |
| Gender | 1.397 | 0.449 | 9.701 | 4.043 (1.679–9.739) | 0.002** |
| Current smoking† | 0.300 | 0.463 | 0.419 | 1.349 (0.545–3.343) | 0.518 |
| Current alcohol drinking‡ | -0.267 | 0.424 | 0.397 | 0.765 (0.333–1.758) | 0.529 |
| Height (m) | 0.024 | 0.028 | 0.714 | 1.024 (0.969–1.803) | 0.398 |
| Weight (kg) | -0.016 | 0.016 | 1.055 | 0.984 (0.953–1.015) | 0.304 |
| BMI (kg/m2) | 0.000 | 0.026 | 0.000 | 1.000 (0.950–1.053) | 0.999 |
| PCT (ng/mL) | 7.821 | 0.435 | 322.948 | 2491.808 (1061.884-5847.257) | 0.000** |
| IL-6 (pg/mL) | 0.643 | 0.106 | 36.961 | 1.903 (1.546–2.341) | 0.000** |
| CRP (mg/mL) | 0.475 | 0.081 | 34.343 | 1.608 (1.372–1.885) | 0.000** |
**P < 0.01. †Current smoking was defined as smoking cessation for less than 6 months and continuous or cumulative smoking for 6 months or more; ‡Current alcohol drinking was defined as having consumed wine at least once in the past week with a volume of alcohol exceeding 50 ml
Abbreviations: CRP C reactive protein, IL-6 Interleukin-6, and PCT Procalcitonin
Discussion
This study systematically analyzed the distribution characteristics of serum 25(OH)D levels and their correlations with multiple biomarkers, inflammatory factors, age, gender, seasons and other factors based on data in 2,080 subjects from high-altitude, hypoxic areas. The research results revealed that vitamin D deficiency (VDD) was extremely prevalent (83.65%) in this population, with the average 25(OH)D level reaching only 13.99 ng/mL, indicating that the overall population suffered from insufficient vitamin D status (Table 1). This finding is somewhat comparable to the results of studies conducted in other countries or regions [5], yet the VDD rate is relatively high, which may be attributed to geographical location, sunshine duration, dietary habits, lifestyle and other relevant factors.
In terms of inflammatory factors, significant differences were observed in the levels of PCT, IL-6 and CRP across the vitamin D deficient group, insufficient group and sufficient group; these inflammatory markers showed a gradual declining trend as 25(OH)D levels increased (Table 3). Further correlation analyses demonstrated that PCT, IL-6 and CRP were significantly negatively correlated with 25(OH)D, and such correlations remained statistically significant even after adjusting for confounding factors including age, gender, body weight, smoking, alcohol consumption and seasons (Table 6). Studies have confirmed that VDD disrupts the balance between pro-inflammatory and anti-inflammatory factors, and is involved in the onset and progression of chronic inflammatory diseases, autoimmune disorders and metabolic syndrome [19–21], vitamin D deficiency or insufficiency is associated with elevated inflammatory markers and increased oxidative stress in children and adolescents [22]. Studies have shown that low vitamin D levels increase the risk of acute respiratory tract infections, COVID-19-related illnesses, inflammatory bowel disease, systemic lupus erythematosus and other autoimmune diseases. Findings from observational studies suggest that vitamin D supplementation inhibits the production and expression of cytokines such as IL-6, IL-8, TNF-α, CRP, and γ-interferon [23–25], which helps prevent a variety of infectious and autoimmune disorders [26, 27]. Our findings support the hypothesis that vitamin D may play a vital role in regulating inflammatory responses, which is consistent with the previous viewpoint that vitamin D exerts immunomodulatory functions.
Logistic regression analysis further confirmed that gender, PCT, IL-6 and CRP were independent risk factors for vitamin D deficiency (Table 7). Among them, females had a significantly higher risk of vitamin D deficiency than males (OR = 4.043). In addition, the OR value of PCT was extremely high (2491.808), indicating that it might have strong predictive value for vitamin D deficiency; nevertheless, cautious interpretation was required due to its wide confidence interval, which could be affected by sample distribution or extreme values.
Regarding population differences, age and gender were identified as significant influencing factors of VDD prevalence [28]. In the age and gender stratified analysis (Tables 4 and 5), there was no significant difference in 25(OH)D levels across different age groups, whereas a notable gender difference was observed. Males exhibited higher 25(OH)D levels than females, and the prevalence of vitamin D deficiency (VDD) was higher in females (87.95% vs. 77.47%). Similarly, residents in Jinzhong City, China, commonly suffer from vitamin D deficiency in winter; women are more likely to have insufficient vitamin D levels compared with men [29]. Such gender differences are probably ascribed to varied daily routines. Lower outdoor exposure, clothing styles blocking ultraviolet radiation, use UV sunscreen, and hormonal variations jointly affect vitamin D synthesis and metabolism in women [30, 31]. It is thus recommended that female populations receive priority in vitamin D deficiency screening and intervention programs.
Seasonal variation exerted a statistically significant effect on 25(OH)D levels, which peaked in summer and reached the trough in winter (Fig. 1). This finding is consistent with the established seasonal pattern linking sunlight exposure to vitamin D synthesis [32]. Although the difference between spring and winter was non-significant, the overall trend was in line with expectations, implying that vitamin D supplementation strategies should be intensified during winter and spring.
Notably, no significant intergroup differences were detected between vitamin D levels and indicators including liver function (ALT, AST), renal function (BUN, CRE), blood lipids (TC, TG, HDL-C, LDL-C) and minerals (Ca, P, Mg) (Table 2). This indicates that vitamin D deficiency may not directly affect these metabolic indicators, or its effect size was weak in the current study sample.
In conclusions, analysis of data from 2,080 subjects in this study reveals that vitamin D deficiency is extremely prevalent in this population, with a deficiency rate reaching 83.65% and a mean serum 25(OH)D concentration of merely 13.99 ng/mL. Vitamin D deficiency is significantly correlated with elevated levels of inflammatory markers including PCT, IL-6 and CRP, and these inflammatory factors act as independent risk factors for vitamin D deficiency. Female gender, as well as winter and spring seasons, are also important contributing factors to low vitamin D levels. No significant differences in vitamin D levels are observed across different age groups, whereas a notable gender disparity exists, with females facing a substantially higher risk of vitamin D deficiency than males. In summary, vitamin D deficiency exhibits a high prevalence in the studied population and is closely associated with systemic inflammatory status. It is recommended that enhanced screening and regular monitoring of vitamin D levels be implemented for high-risk groups, particularly females and individuals assessed during winter and spring, alongside timely intervention through vitamin D supplementation. Future studies could further investigate the intervention efficacy of vitamin D supplementation on inflammatory levels and related diseases, as well as explore its heterogeneous impacts across distinct subgroups.
Limitations
Several limitations are inherent to this study. First, the study sample was recruited from a single region and a specific population, restricting the generalizability of the findings. Second, key factors capable of influencing 25(OH)D concentrations, such as sunlight exposure duration, frequency of outdoor activities and sun protection practices, were not measured, leading to residual confounding bias. Third, biomarkers that may modulate the association between vitamin D and inflammation, including parathyroid hormone (PTH) and vitamin D binding protein (DBP), were not tested, which limits the in-depth exploration of underlying mechanisms. Fourth, the odds ratio (OR) of PCT derived from the Logistic regression analysis is extremely high accompanied by a wide confidence interval, calling for cautious interpretation. Finally, the P-values of some biochemical indicators (e.g., GLU, BUN) are close to the critical threshold of 0.05, which may indicate potential trends that warrant further verification via larger sample sizes in future research. Prospective cohort studies or randomized controlled trials can be conducted subsequently to further validate the causal effect of vitamin D supplementation on reducing inflammatory levels and improving clinical outcomes.
Acknowledgements
Authors special thanks go to all participants in this study.
Abbreviations
- VDD
Vitamin D deficiency
- UVB
Ultraviolet B
- CRP
C reactive protein
- IL-6
Interleukin-6
- PCT
Procalcitonin
Authors’ contributions
Qiong Ye and Jimei Li contributed to data curation, formal analysis, investigation, and writing—original draft. Jimei Li was responsible for funding acquisition, investigation, and writing—review & editing. Qiong Ye, Jimei Li, and Ying Ju participated in the investigation.
Funding
This work was supported by “Kunlun Talents, High-End Innovation, and Entrepreneurship Project.” of 2023 in Qinghai Province (Grant number 2305999903 − 0102).
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Declarations
Ethical approval and consent to participate
This study was approved by the Ethics Committee of Qinghai Provincial People’s Hospital (Approval No. 2023-036). The research protocol complies with the Declaration of Helsinki, and all participants signed informed consent forms.
Consent for publication
Written informed consent has been obtained from the patients to publish this paper.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Qiong Ye and Jimei Li contributed equally to this work.
References
- 1.Holick M F. Vitamin D deficiency[J]. N Engl J Med. 2007;357(3):266–81. [DOI] [PubMed] [Google Scholar]
- 2.Holick M F, Binkley N C, Bischoff-Ferrari H A, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline[J]. J Clin Endocrinol Metab. 2011;96(7):1911–30. [DOI] [PubMed] [Google Scholar]
- 3.Zou Y, MU M, Zhang S, et al. Vitamin D3 suppresses astrocyte activation and ameliorates coal dust-induced mood disorders in mice[J]. J Affect Disord. 2022;303:138–47. [DOI] [PubMed] [Google Scholar]
- 4.Cui A, Zhang T, Xiao P, et al. Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants[J]. Front Nutr. 2023;10:1070808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Cashman K D. Global differences in vitamin D status and dietary intake: a review of the data[J]. Endocr connections. 2022;11(1):e210282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.de Cureau F V Oliveiracl, Cople-Rodrigues C D S, et al. Prevalence and factors associated with hypovitaminosis D in adolescents from a sunny country: Findings from the ERICA survey[J]. J Steroid Biochem Mol Biol. 2020;199:105609. [DOI] [PubMed] [Google Scholar]
- 7.Rucker D, Allan J A, Fick G H, et al. Vitamin D insufficiency in a population of healthy western Canadians[J]. Volume 166. CMAJ: Canadian Medical Association journal = journal de l’Association medicale canadienne; 2002. pp. 1517–24. 12. [PMC free article] [PubMed] [Google Scholar]
- 8.Subramanian A, Burrowes H B, Rumph J T, et al. Vitamin D Levels in the United States: Temporal Trends (2011–2018) and Contemporary Associations with Sociodemographic Characteristics (2017–2018)[J]. Nutrients. 2024;16(19):3414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.WU T. The Qinghai-Tibetan plateau: how high do Tibetans live?[J]. High Alt Med Biol, 2001,2(4): 489–99. [DOI] [PubMed]
- 10.Moore LG. Measuring high-altitude adaptation[J]. J Appl Physiol (Bethesda Md : 1985). 2017;123(5):1371–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hossein-Nezhad A, Holick M F. Vitamin D for health: a global perspective[J]. Mayo Clinic proceedings, 2013,88(7): 720–755. [DOI] [PMC free article] [PubMed]
- 12.Huang P, KE G, Lin X, et al. Correlation analysis between vitamin A, D, and E status with altitude, seasonal variation, and other factors, among children aged 0–6 years in a Chinese population living in the Tibetan plateau of Ganzi prefecture[J]. J Clin Lab Anal. 2022;36(9):e24620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Eltzschig H K Carmelietp. Hypoxia and inflammation[J]. N Engl J Med. 2011;364(7):656–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.EL Amine B, Fournier J. Cerebral oxidative stress, inflammation and apoptosis induced by intermittent hypoxia: a systematic review and meta-analysis of rodent data[J]. Eur respiratory review: official J Eur Respiratory Soc. 2024;33(174):240162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Boira I. Sleep and Respiratory Infections[J]. Semin Respir Crit Care Med. 2025;46(2):170–8. [DOI] [PubMed] [Google Scholar]
- 16.LI C, Shi S. Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances[J]. Front Endocrinol. 2024;14:1224396. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Hartmann G, Tschöp M, Fischer R, et al. High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein[J]. Cytokine. 2000;12(3):246–52. [DOI] [PubMed] [Google Scholar]
- 18.Chinese Society of Osteoporosis and Bone Mineral Research, Chinese Medical Association. Consensus on Clinical Application of Vitamin D and Its Analogs (2025 Edition)[J]. Chin J Osteoporos Bone Mineral Res. 2025;18(05):497–517. [Google Scholar]
- 19.Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system[J]. Nat Clin Pract Rheumatol. 2008;4(8):404–12. [DOI] [PubMed] [Google Scholar]
- 20.Barrea L, Muscogiuri G, Laudisio D, et al. Influence of the Mediterranean Diet on 25- Hydroxyvitamin D Levels in Adults[J]. Nutrients. 2020;12(5):1439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Zuk A M, Liberda E N, Tsuji L J. Examining chronic inflammatory markers on blood pressure measures in the presence of vitamin D insufficiency among indigenous cree adults: results from the cross-sectional Multi-Community Environment-and-Health Study in Eeyou Istchee, Quebec, Canada[J]. BMJ open. 2021;11(1):e043166. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Filgueiras M S, Rocha N P, Novaes J F, et al. Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review[J]. Crit Rev Food Sci Nutr. 2020;60(4):660–9. [DOI] [PubMed] [Google Scholar]
- 23.Evans K N Nguyenl, Chan J, et al. Effects of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on cytokine production by human decidual cells[J]. Biol Reprod. 2006;75(6):816–22. [DOI] [PubMed] [Google Scholar]
- 24.Díaz L, Noyola-Martínez N, Barrera D, et al. Calcitriol inhibits TNF-alpha-induced inflammatory cytokines in human trophoblasts[J]. J Reprod Immunol. 2009;81(1):17–24. [DOI] [PubMed] [Google Scholar]
- 25.Alkharfy K M, AL-Daghri N M Yakoutsm, et al. Calcitriol attenuates weight-related systemic inflammation and ultrastructural changes in the liver in a rodent model[J]. Volume 112. Basic & clinical pharmacology & toxicology; 2013. pp. 42–9. 1. [DOI] [PubMed]
- 26.Johnson C R, Thacher T D. Vitamin D. immune function, inflammation, infections and auto-immunity[J]. Paediatrics Int child health. 2023;43(4):29–39. [DOI] [PubMed] [Google Scholar]
- 27.Ganmaa D, Enkhmaa D. Vitamin D, respiratory infections, and chronic disease: Review of meta-analyses and randomized clinical trials[J]. J Intern Med. 2022;291(2):141–64. [DOI] [PubMed] [Google Scholar]
- 28.Sanghera D K, Sapkota B R, Aston C E, et al. Vitamin D Status, Gender Differences, and Cardiometabolic Health Disparities[J]. Ann Nutr Metab. 2017;70(2):79–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Yan X, Zhang N, Cheng S, et al. Gender Differences in Vitamin D Status in China[J]. Med Sci monitor: Int Med J experimental Clin Res. 2019;25:7094–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Wierzbicka A, Oczkowicz M. Sex differences in vitamin D metabolism, serum levels and action[J]. Br J Nutr. 2022;128(11):2115–30. [DOI] [PubMed] [Google Scholar]
- 31.Rapuri P B, Gallagher JC. Effect of vitamins D2 and D3 supplement use on serum 25OHD concentration in elderly women in summer and winter[J]. Calcif Tissue Int. 2004;74(2):150–6. [DOI] [PubMed] [Google Scholar]
- 32.Won J W, Jung S K, Jung I A, et al. Seasonal Changes in Vitamin D Levels of Healthy Children in Mid-Latitude, Asian Urban Area[J]. Volume 24. Pediatric gastroenterology, hepatology & nutrition; 2021. pp. 207–17. 2. [DOI] [PMC free article] [PubMed]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.