Vitamin A and D deficiencies in Tibetan vs. non-Tibetan children: roles of altitude, gender, and season in Sichuan Province

Abstract

Background

Vitamin deficiencies significantly impact children’s growth and development, particularly in high-altitude regions. This study investigated the prevalence and patterns of vitamin A and D deficiencies among children in Tibetan versus non-Tibetan regions of Sichuan Province, China, considering the influences of altitude, gender, and seasonal variations.

Methods

A case-control study was conducted comparing 995 Tibetan children from Garze Prefecture (altitude > 2000 m) with 995 age- and sex-matched non-Tibetan children from Luzhou City during 2017–2019. Vitamin A deficiency was defined as serum retinol < 0.70 µmol/L, and vitamin D deficiency as 25-hydroxyvitamin D < 50 nmol/L.

Results

Tibetan children showed significantly higher rates of vitamin A (47.7% vs. 21.0%) and D (19.8% vs. 10.7%) deficiency compared to non-Tibetan children. Vitamin A and Vitamin D deficiency were more frequent in higher altitudes, with vitamin A (OR 5.2, 95% CI 2.44–11.09) and D deficiency (OR 2.47, 95% CI 1.28–4.77). Female Tibetan children demonstrated higher vitamin D deficiency risk, while summer and autumn were associated with lower vitamin D deficiency risk (OR 0.43, 95% CI 0.29–0.65).

Conclusions

This study reveals substantial disparities in vitamin A and D status between Tibetan and non-Tibetan children, with altitude, gender, and seasonal factors playing crucial roles. These findings emphasize the need for targeted nutritional interventions considering multiple environmental and demographic factors in high-altitude regions.

Optimal micronutrient status during childhood is crucial for physical growth, cognitive development, and long-term health outcomes [1]. Vitamin D is particularly essential fat-soluble vitamins that play vital roles in immune function, vision, bone health, and antioxidant defense systems [2]. Vitamins A plays an essential role in human growth and development, immunity, and vision. Vitamin A deficiency (VAD) leads to a debilitating disease known as nyctalopia, which is still a major problem in many developing countries [3]. An estimated 250 000–500 000 children who are vitamin A-deficient become blind every year, and half of them die within 12 months of losing their sight [3]. Recent global estimates indicate that 29% of preschool-age children suffer from vitamin A deficiency in low-income and middle-income countries in 2013 [4], while vitamin D deficiency affects up to 1 billion people worldwide [5]. These deficiencies often coexist and demonstrate remarkable seasonal variations of vitamin D that being lowest during winter and early spring [6, 7]. In addition, there are varying vitamin A status corresponding to seasonal availability of carotenoid-rich foods during non-harvest months. For example, rainy season (June to November) is associated with a high risk of VAD for children living in west Africa and a possible explanation can be low food availability [8]. There are studies from high-altitude regions reporting significantly lower vitamin D levels [9].

In China, despite remarkable economic progress, significant disparities in children’s nutritional status persist across regions and ethnic groups, raising important questions about health equity [10]. The Tibetan Autonomous regions of Sichuan Province present unique geographical, cultural, and dietary characteristics that may influence children’s micronutrient status [11]. These areas are characterized by high altitude (ranging from 3000 to 4500 m), limited access to diverse food sources, and distinct dietary patterns shaped by traditional Tibetan culture [12]. Previous research has demonstrated that high-altitude residence can significantly impact vitamin D synthesis due to increased UV radiation exposure [5], while traditional Tibetan dietary practices may affect vitamin A intake patterns. The limited fresh vegetables due to harsh high-altitude environments and highland barley-based dietary pattern restricts access to vitamin A sources such as liver, eggs, fruits, and vegetables [13]. Some studies report decreased 25-OH-D levels in Tibetans at high altitude and Turkish pregnant women at moderate altitude, but without comparisons of the same area population at lower altitudes [14–16]. There is also research in Africa that significant seasonal variations in vitamin A status correlating with dietary changes [8]. However, comprehensive comparative research examining multiple vitamin deficiencies between Tibetan and non-Tibetan areas remains limited, particularly concerning seasonal variations and impact on children’s nutritional status.

Understanding these disparities is crucial for several reasons. First, the unique geographical and cultural context of Tibetan regions may reveal previously unknown interactions between altitude, ethnicity, and micronutrient metabolism. The Plateau’s extreme hypoxic, cold, and resource-scarce environment has driven genetic adaptations in Tibetans. Genomic studies have revealed divergent alleles in hypoxia-responsive pathways, demonstrating evolutionary selection distinct from lowland populations [17–18]. It may result in significant disparities in vitamin levels between Tibetan populations and lowland inhabitants. Second, summer vs. winter levels in these high-altitude areas may differently impact vitamin status compared to lower-altitude regions, necessitating season-specific intervention strategies. Third, the coexistence of multiple vitamin deficiencies may have synergistic effects on children’s health outcomes, particularly in ethnically diverse regions where traditional dietary practices interact with geographical constraints. Finally, addressing these nutritional disparities is essential for promoting health equity and ensuring that children in ethnic minority regions have equal opportunities for optimal growth and development.

Therefore, this study aims to investigate the prevalence and seasonal patterns of vitamin A, D deficiencies among children in Tibetan autonomous regions compared to non-Tibetan areas in Sichuan Province. This research will provide insights for developing targeted nutritional interventions and inform evidence-based policies to address health disparities in high-altitude regions of China.

Methods

Data sources and participants

This study utilized data from two sources in Sichuan Province, China. We obtained the first dataset from a 2017–2019 nutritional survey conducted in Tibetan autonomous regions (Two counties in Garze Prefecture, Sichuan Province, namely Xiangcheng County and Daocheng County. Xiangcheng County includes all 12 townships and Daocheng County includes all 14 townships, all at an altitude of over 2000 m above sea level), which included children aged 1–10 years old. All children were involved in a comprehensive health checkup. The laboratory data of serum samples were obtained from the medical examination center in Garzi Tibetan Autonomous Prefecture during the period 2017–2019. We obtained the general epidemiological data through a questionnaire survey on parents of children who visited the physical examination center. The following conditions were excluded: metabolic diseases (including diabetes, thyroid disorders, and inborn errors of metabolism), tuberculosis, kidney disease, liver disease and malabsorption syndromes. The second dataset was drawn from routine child health checkups performed in Luzhou City, a non-Tibetan region of Sichuan Province, which consisted of Han Chinese, during the same time period. All guardians signed informed consent forms, and this study was approved by the Ethics Committee of Luzhou People’s Hospital (approval number: 20171103). A case-control study design was employed, matching Tibetan children 1:1 with non-Tibetan children from Luzhou by age and sex. This resulted in a final sample of 995 Tibetan children and 995 non-Tibetan children (Fig. 1). The geographical locations of Garze (Tibetan Plateau) and Luzhou (Sichuan Basin) was demarcated in Fig. 2.

Fig. 1.

Flowchart

Fig. 2.

Geographical distribution of the study areas

The following potential confounding factors were systematically analyzed in both datasets:

1. Demographic characteristics: Age, sex, and residential altitude.

2. Health-related covariates: Vitamin A deficiency; Vitamin D deficiency; Seasonal blood sample collection.

For cross-sectional studies, the sample size calculation method was as follows:

n: Sample size per group; δ = 0.1; p = 0.8.

The theoretical minimum sample size required was 62 per group. However, to enhance statistical power and improve the robustness of our findings, we pragmatically increased the sample size.

Measures

Vitamin A deficiency was defined as serum retinol concentration < 0.70 µmol/L, as per the World Health Organization (WHO) criteria. Vitamin D deficiency was classified as serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/L, according to the Endocrine Society clinical practice guidelines (Holick et al., 2011).

Statistical Analysis.

Data was analyzed using SPSS Statistics 26.0. All sociodemographic characteristics were categorical and were expressed as frequencies (and percentages). Descriptive statistics were calculated to summarize the prevalence of vitamin A and D deficiencies in different groups. A multivariate stepwise logistic regression model was constructed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for vitamin deficiencies, adjusting for potential confounders. Subgroup analyses were performed to examine seasonal variations in vitamin status between the two groups. All tests were two-tailed and statistical significance was considered for p values < 0.05.

Result

Sociodemographic characteristics

The study included a total of 1,990 children, evenly divided into Tibetan (n = 995) and non-Tibetan (n = 995) groups. The demographic characteristics were well-matched, with a mean age of 3.10 years and a nearly balanced gender distribution (Tibetan: 46.4% male, 53.6% female; non-Tibetan: 46.4% male, 53.6% female) (Table 1).

Table 1.

Sociodemographic characteristics of Tibetan and Non-Tibetan children

	Tibetan (N = 995)	Non-Tibetan (N = 995)	p value
	n (%)	n (%)
Child age	3.10 ± 1.92 (Mean ± SD)	3.10 ± 1.92 (Mean ± SD)	1.000
Child sex
Male	462 (46.4)	462 (46.4)	1.000
Female	533 (53.6)	533 (53.6)
Seasonal blood sample collection			< 0.001
Spring	48(4.8)	206 (20.7)
Summer	792 (79.6)	210 (21.1)
Autumn	59 (5.9)	330 (33.2)
Winter	96 (9.6)	249 (25.0)

Abbreviations: N, Number; SD, Standard Deviation

Notably, significant differences were observed in seasonal blood sample collection between the two groups (p < 0.001). While summer was the predominant sampling season for Tibetan children (79.6%), non-Tibetan children were more evenly distributed across seasons, with 20.7% in spring, 21.1% in summer, 33.2% in autumn, and 25.0% in winter.

Vitamin deficiency status

Comparative analysis revealed substantial disparities in vitamin A and D deficiency rates between Tibetan and non-Tibetan children (Table 2). For Vitamin A Deficiency, Tibetan children showed significantly higher deficiency rates compared to non-Tibetan children (47.7% vs. 21.0%, p < 0.001). For Vitamin D Deficiency, Tibetan children demonstrated higher vitamin D deficiency rates (19.8% vs. 10.7%, p < 0.001).

Table 2.

Vitamin A\D’ s status

Variables	Vitamin A n (%)			Vitamin D n (%)
	Deficiency (< 0.7)	Normal(≥ 0.7)	p value	Deficiency (< 50)	Normal(≥ 50)	p value
District
Tibetan	475 (47.7)	520 (52.3)	< 0.001	197 (19.8)	798 (80.2)	< 0.001
Non-Tibetan	209 (21.0)	786 (79.0)		106 (10.7)	889 (89.3)
Child sex
Male	394 (37.0)	634 (68.6)	0.005	132 (12.4)	934 (87.6)	< 0.001
Female	290 (31.4)	634 (68.6)		171 (18.5)	753 (81.5)
Age group
1–3	401 (32.0)	853 (68.0)	0.014	25 (2.0)	1229 (98.0)	0.379
4–6	237 (38.6)	377 (61.4)		8 (1.3)	606 (98.7)
7–9	46 (37.7)	76 (62.3)		1 (0.8)	121 (99.2)
Seasonal blood sample collection
Spring	40 (15.7)	214 (84.3)	< 0.001	52 (20.5)	202 (79.5)	< 0.001
Summer	486 (48.5)	516 (51.5)		175 (17.5)	827 (82.5)
Autumn	84 (21.6)	305 (78.4)		28 (7.2)	361 (92.8)
Winter	74 (21.4)	271 (78.6)		48 (13.9)	297 (86.1)
	684 (34.4)	1306 (65.6)		303 (15.2)	1687 (84.8)

Multivariate analysis of Tibetan children revealed several significant associations (Table 3). For Vitamin A Deficiency, children living at 3000–4000 m and 4000–5000 m altitudes had significantly higher risks of vitamin A deficiency (OR 1.83, 95% CI 1.35–2.38; OR 5.21, 95% CI 2.44–11.09, respectively). For Vitamin D Deficiency, female was associated with increased vitamin D deficiency risk (OR 1.81, 95% CI 1.31–2.50). Children aged 4–6 years showed higher vitamin D deficiency (OR 1.45, 95% CI 1.01–2.09). Higher altitudes (4000–5000 m) significantly increased vitamin D deficiency risk (OR 2.47, 95% CI 1.28–4.77).

Table 3.

Vitamin A\D’ s status in Tibetan

	Vitamin A deficiency		Vitamin D deficiency
Variable	OR	95CI	OR	95CI
Child sex
Male	1
Female	0.922	0.70–1.21	1.81	1.31–2.50
Age group
1–3	1		1
4–6	1.22	0.89–1.62	1.45	1.01–2.09
7–9	1.51	0.82–2.72	0.87	0.40–1.88
Seasonal blood sample collection
Winter/Spring	1
Summer/Autumn	0.27	0.18–0.42	1.21	0.77–1.90
Altitude
2000–3000	1		1
3000–4000	1.83	1.35–2.38	0.72	0.51–1.01
4000–5000	5.21	2.44–11.09	2.47	1.28–4.77

For non-Tibetan children, the patterns differed (Table 4). Female children demonstrated a lower risk of vitamin A deficiency (OR 0.62, 95% CI 0.45–0.85). Female children showed a trend towards higher vitamin D deficiency (OR 1.37, 95% CI 0.91–2.06). Summer and autumn seasons were associated with lower vitamin D deficiency risk (OR 0.43, 95% CI 0.29–0.65).

Table 4.

Vitamin A\D’ s status in Non-Tibetan

	Vitamin A deficiency		Vitamin D deficiency
Variable	OR	95CI	OR	95CI
Child sex
Male	1
Female	0.62	0.45–0.85	1.37	0.91–2.06
Age group
1–3	1		1
4–6	1	0.72–1.40	0.81	0.51–1.27
7–9	0.79	0.40–1.57	0.83	0.32–2.17
Seasonal blood sample collection
Winter/Spring	1
Summer/Autumn	1.07	0.78–1.46	0.43	0.29–0.65

Discussion

This study reveals significant disparities in vitamin A, and D nutritional status between Tibetan and non-Tibetan children, providing critical insights into micronutrient metabolism in highland regions. The unique geographical environment, complex ecosystem, and distinctive lifestyle of the plateau collectively shape children’s nutritional metabolism, a complexity that far exceeds our previous understanding.

It reveals higher prevalence rates of vitamin A and D deficiencies among Tibetan children compared to non-Tibetan children. Specifically, 47.7% of Tibetan children were vitamin A deficient, more than twice the rate observed in non-Tibetan children (21.0%). Similarly, vitamin D deficiency affected 19.8% of Tibetan children, higher than the 10.7% found in non-Tibetan children. These findings notably exceed the vitamin A deficiency in 9.23% of children aged under 5 years [19], and vitamin D deficiency in 14% of children aged under 7 years [20] in China.

Multiple factors may contribute to these elevated deficiency rates. The high-altitude environment of the Tibetan Plateau, while characterized by intense UV radiation, paradoxically may not protect against vitamin D deficiency. A previous study has reported higher prevalence of vitamin D deficiency among children in low sunlight exposure regions [21], but our findings show inconsistency with this observation. The traditional attire for Tibetan, including hats, Tibetan robes and boots, may significantly reduce direct skin exposure to sunlight [22]. Our finding aligns with previous studies in high-altitude regions of Nepal, where similar vitamin D deficiency patterns were observed despite abundant sunlight exposure [23]. Additionally, the relative geographic isolation and economic constraints of Tibet may limit access to vitamin-rich food sources. The dietary intake of aquatic products, vegetables, and fruits among the Tibetan population exhibit severe deficiencies, with consumption levels falling 95%, 70%, and 52.5% below recommended values, respectively [12].The harsh plateau climate limits local cultivation of vegetables and fruits, while extremely low aquatic product consumption is primarily attributed to religious and cultural reasons [24].The traditional Tibetan diet, predominantly based on barley, yak meat, while culturally significant, may not provide adequate micronutrient diversity. Given the relatively lower socioeconomic status (SES) in Tibetan regions, the population may face increased nutritional vulnerability due to limited access to diverse food sources. Regarding SES and vitamin intake, studies have shown that SES was the strongest predictor of vitamin D status, with disadvantaged individuals having 2.18 times higher odds of deficiency compared to affluent individuals [25]. Similar results have been identified in other countries [26–28]. Vitamin D intake is lower among children from low-income families, likely due to reduced consumption of vitamin D-rich foods such as fish, meat, and fortified products [28]. While we discuss the potential impact of SES, this factor is not quantitatively measured or adjusted for in analyses. It likely interacts with altitude and ethnicity in complex ways that merit further investigation. The healthcare conditions in Tibetan areas have also contributed to the relative underdevelopment in accessing nutritional supplements and nutritional knowledge among local residents [29].

The relationship with altitude on vitamin metabolism emerges as one the most striking finding of our research. As altitude progressively increased, the risk of vitamin A deficiency demonstrate a significant gradient increase, particularly in high-altitude regions between 4000 and 5000 m above sea level, where the risk of vitamin A deficiency is 5.21 times higher compared to lower-altitude areas. In addition, in high-altitude regions between 4000 and 5000 m above sea level, the risk of vitamin D deficiency is 2.47 times higher compared to lower-altitude areas. Those children are at particularly high risk of vitamin D deficiency because the mountainous topography results in a cool climate that may lead to less ultra violet B skin exposure [30]. The contradictory findings on Vitamin D deficiency at different altitudes highlight the complexity of this relationship, where factors such as local climate, cultural practices, and behavioral patterns may have a greater influence than altitude alone, as evidenced by high deficiency rates in high-altitude Indian population [31] and Argentinean [32], but increased deficiency in lower-altitude Saudi populations [33]. Limited research exists on vitamin A deficiencies at high altitudes, where reduced accessibility to fresh fruits and vegetables due to geographical constraints. This finding transcends mere numerical variation, revealing the profound influence of highland environments on human micronutrient absorption and metabolism. While previous studies primarily focus on highland environments, our research is the first to systematically quantify the differential relationship with altitude gradients on children’s vitamin status, providing a more precise theoretical foundation for nutritional interventions in highland regions.

Gender factors present remarkably differentiated patterns of vitamin deficiency. Among Tibetan children, female children exhibit a higher risk of vitamin D deficiency, potentially related to their daily activity patterns. Boys are naturally active, participate in physical exercise for a longer period of time and have higher physical activity levels and chance to sunlight [34]. Research among Irish children reveal that females are 1.57 times more likely to be vitamin deficient compared to males [25]. Female children typically have lower vitamin D status, attributable to reduced consumption of both vitamin D-fortified foods and overall dietary vitamin D intake [35]. In contrast, non-Tibetan children show females having a lower risk of vitamin A deficiency. These differences are unlikely to be mere statistical coincidences but may instead reflect the distinctive nutritional metabolism, genetic backgrounds, and environmental adaptability of different populations. Globally, research found that men have higher intake inadequacies than women for vitamin A [36].

Seasonal variations similarly exerted a non-negligible influence on vitamin status. Summer and autumn seasons significantly reduce vitamin D deficiency risks among non-Tibetan children, potentially associated with seasonal sunlight exposure, increased outdoor activities, and seasonal dietary structure variations. Studies also demonstrate increased probability of vitamin D deficiency during winter months [25, 37]. While non-Tibetan areas demonstrate the typically expected seasonal variation in vitamin D status, this seasonal trend is notably absent in Tibetan regions. The environmental advantage appears to be offset by traditional Tibetan clothing practices and year-round dietary patterns, as evidenced by the consistently higher vitamin D deficiency rates throughout the year in Tibetan children.

Our study reveals a seasonal pattern in vitamin A deficiency among Tibetan children, with lower prevalence rates during summer and autumn compared to winter and spring months. This seasonal variation is not observed in non-Tibetan regions. Research has consistently shown higher prevalence of vitamin A deficiency during winter months compared to summer [38]. This seasonal pattern may be attributed to variations in the availability and consumption of vitamin A-rich foods across seasons. Traditional Tibetan practices of vegetable preservation for winter consumption might not adequately maintain vitamin A content, leading to higher deficiency rates in winter and spring. Additionally, the summer grazing patterns of yak and cattle in highland pastures may result in higher vitamin A content in dairy products during these seasons [39], as fresh grass contains more β-carotene compared to dried winter fodder. The absence of such seasonal variation in non-Tibetan regions may be explained by their more stable year-round access to diverse food sources and modern food preservation methods. This finding surpasses traditional nutritional research perspectives, offering novel research insights into how seasonal factors impact micronutrient elements.

The results extend beyond descriptive analysis, carrying significant practical guidance implications. Nutritional interventions for children in highland regions should not adopt a one-size-fits-all approach but rather develop personalized nutritional strategies based on multidimensional factors including altitude, gender, and season. For instance, 4-6-year-old Tibetan girls might require more precise and intensive vitamin D supplementation protocols. Moreover, this study provides more refined stratification bases for future nutritional intervention research.

Despite providing crucial insights into the nutritional status of highland children, the study is not without limitations. First, the cross-sectional study design restricts our tracking of dynamic nutritional changes and prevents establishing causality. Future longitudinal studies would better capture seasonal and developmental trends in vitamin status among these populations. Second, the geographical sample range remains relatively limited. It focuses on specific counties in Garze Prefecture and Luzhou City, which may not fully represent the broader Tibetan and non-Tibetan populations in Sichuan Province due to geographic and cultural heterogeneity within these groups. Third, our study lacks detailed dietary intake and lifestyle metrics (e.g., sun exposure, clothing habits, food availability). These data will provide valuable insights into the mechanisms behind the observed vitamin deficiencies and will be incorporated in future research. Fourth, non-homogenous season distribution is a limitation. We acknowledge the seasonal sampling imbalance between populations, with Tibetan children predominantly sampled in summer (79.6%) while non-Tibetan children have more balanced seasonal sampling. This imbalance may affect seasonal comparisons and will be addressed in future studies through more balanced sampling designs. Fifth, our study did not investigate potential genetic differences in vitamin metabolism between ethnic groups, which could influence deficiency rates independent of environmental factors. Future studies incorporating genetic analyses will provide valuable insights into potential adaptive mechanisms. Sixth, while higher vitamin D deficiency despite increased UV radiation at high altitudes, our study did not directly measure behavioral factors (e.g., traditional clothing practices) that might explain this paradox. These factors represent important areas for future research.

In conclusion, through multidimensional analysis, this research comprehensively reveals the complex ecological landscape of vitamin nutrition in highland children. The research findings will provide more precise and personalized scientific bases for nutritional interventions for children in highland regions, bearing significant practical importance for improving children’s health. The results underscore the urgent need for targeted nutritional interventions in Tibetan regions, suggesting that comprehensive approaches including nutrition education, food accessibility improvements, and appropriate supplementation strategies should be implemented.

Micronutrient supplementation in high-altitude communities may improve vitamin status in children. The dietary diversification strategies incorporating local traditional foods combined with fortified products will be promising in addressing multiple micronutrient deficiencies. From a research perspective, systematic analysis of dietary patterns through advanced nutritional epidemiology methods is recommended to better understand complex food component interactions and their health implications. Future public health initiatives should prioritize implementing robust nutritional surveillance programs targeting vulnerable populations and developing micronutrient deficiency prevention frameworks.

Author contributions

PH, YZ, DW, and XL contributed to the study conception and design, as well as material preparation and data collection and commented on previous versions of the manuscript. Data analysis was performed by YZ and YH. The first draft of the manuscript was written by YZ, HC and XZ. All authors read and approved the final manuscript.

Funding

This study was supported by the Sichuan Provincial Health Commission (17PJ276) & Luzhou Science and Technology Program (2022-SYF-66).

Data availability

The data that support the findings of this study are available on request from the corresponding author, XL, upon reasonable request.

Declarations

Ethics approval and consent to participate

The study involving human participants was carried out by the Helsinki Declaration was approved by the Ethics Committee of Luzhou People’s Hospital (approval number: 20171103). Patients/participants provided written informed consent to participate in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.