Two-phase linear relationship and threshold effects between Vitamin E and Vitamin A levels in children aged 0-14 years: a cross-sectional study

Two-phase linear relationship and threshold effects between Vitamin E and Vitamin A levels in children aged 0-14 years: a cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Two-phase linear relationship and threshold effects between Vitamin E and Vitamin A levels in children aged 0-14 years: a cross-sectional study Wenyuan Liu, Qiao Wang, Zhuoling Li, Jishan Zheng, Changshui Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6707714/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Nov, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Background Vitamins E and A are essential fat-soluble micronutrients critical for immune regulation, bone metabolism, and cellular homeostasis. Current evidence highlights significant gaps in understanding their interdependent relationships and the modulatory effects of age, environmental exposures, and physiological status on their systemic bioavailability. Objective To investigate the relationship between Vitamin E and Vitamin A levels in children aged 0–14 years and identify any critical thresholds. Methods This cross-sectional study was conducted from 2018 to 2021 in Ningbo, Zhejiang, China. It involved children aged 0–14 years who attended community health service centers for routine health check-ups. To evaluate the relationship between serum Vitamin E and Vitamin A levels, we performed a multivariate linear regression analysis. Furthermore, a smooth curve fitting approach was employed to investigate the dose-response relationship between Vitamin E and Vitamin A. Results The study included a total of 4,752 participants. Significant variations in baseline Vitamin E and Vitamin A levels were observed across different deficiency categories. The mean Vitamin E level was lowest in the deficiency group (2.4 ± 0.5 µg/mL) and highest in the excess group (7.0 ± 1.6 µg/mL). Similarly, the mean Vitamin A level was lowest in the deficiency group (236.9 ± 60.4 ng/mL) and highest in the excess group (292.4 ± 72.3 ng/mL). A two-phase linear relationship was identified, with a significant threshold effect at a Vitamin E level of 3.579 µg/mL. Below this threshold, the association between Vitamin E and Vitamin A was robust ( β = 35.829, 95% CI: 30.217, 41.441), while above the threshold, the association weakened significantly ( β = 9.828, 95% CI: 8.250, 11.406). The likelihood ratio test confirmed the significance of this threshold effect ( p < 0.001). Conclusions The study identified a significant threshold at 3.579 µg/mL for Vitamin E, beyond which the association with Vitamin A levels stabilizes. This threshold highlights the importance of maintaining optimal Vitamin E levels to support Vitamin A status, particularly in high-risk groups such as older children and those with limited access to Vitamin E-rich foods. Future longitudinal studies are needed to further validate these findings and explore their implications for public health interventions. Health sciences/Diseases Health sciences/Health care Vitamin E Vitamin A Children Micronutrients Threshold Effect Public Health Intervention Figures Figure 1 Background As critical micronutrients, vitamin A (retinoids) and vitamin E (tocopherols) demonstrate pleiotropic biological functions, particularly in immunomodulation, skeletal system homeostasis maintenance, and regulation of cellular proliferation and differentiation processes (1,2,3,4). Their deficiencies are associated with a range of health issues, particularly in children, where growth and development are most critical (5). Despite their importance, the relationship between these two vitamins and the influence of demographic, environmental, and physiological factors on their levels remain complex and not fully understood. Vitamin E, a potent antioxidant, is crucial for protecting cell membranes, supporting immune function, and maintaining neurological health. It is primarily obtained through diet, with vegetable oils, nuts, and green leafy vegetables being rich sources (6). Vitamin E deficiency can lead to neurological disorders, anemia, and increased susceptibility to infections (7). Vitamin A, on the other hand, is vital for vision, immune function, and reproductive health. It is obtained through dietary sources such as liver, fish oils, and dairy products, or synthesized from provitamin A carotenoids found in fruits and vegetables (8,9). Deficiency in Vitamin A is a leading cause of preventable blindness in children and can also result in increased susceptibility to infections and other health complications (10). The metabolism and function of Vitamin E and Vitamin A are closely interrelated. Both vitamins are fat-soluble and share common transport mechanisms in the body. Recent studies have suggested that there may be synergistic effects between these two vitamins, particularly in terms of their antioxidant functions and their roles in immune modulation (11,12). However, the exact nature of their interaction and the potential threshold effects in children have not been adequately explored. Understanding this relationship is crucial for developing effective public health interventions aimed at addressing micronutrient deficiencies in pediatric populations. Globally, micronutrient deficiencies are a significant public health concern, particularly in low- and middle-income countries where access to diverse diets and supplements may be limited (13). In children, these deficiencies can have long-term consequences on growth, development, and overall health outcomes. Previous research has examined the individual roles of Vitamin E and Vitamin A, but there is a paucity of studies investigating their combined effects and potential threshold interactions in children. Identifying such thresholds could have substantial implications for optimizing the status of these vitamins through targeted interventions. This cross-sectional investigation employs population-stratified sampling to elucidate the biphasic dose-response correlation between Vitamin E and Vitamin A concentrations in pediatric cohorts. We postulate a critical serum threshold beyond which retinol homeostasis demonstrates stabilization, as quantified through segmented regression modeling. The dual focus on deficiency epidemiology and micronutrient interaction dynamics aims to advance nutritional biomarker interpretation frameworks, with potential applications in: (1) refining dietary reference intake algorithms, (2) optimizing combined supplementation protocols, and (3) developing age-specific deficiency risk stratification matrices. Methods Study design This cross-sectional study set out to explore the relationship between Vitamin E and Vitamin A levels in children aged 0–14 years (Clinical trial number: not applicable). The sample size was determined to ensure sufficient statistical power for identifying significant associations, thereby underpinning the reliability of the results. Participant recruitment took place from January 1, 2018, to December 31, 2021. This timeframe allowed for a comprehensive capture of the participants' health status at a specific moment, facilitating an accurate analysis of Vitamin E prevalence and its relationship with Vitamin A levels. The study obtained ethical approval from the Ethics Committee of the Affiliated Women and Children’s Hospital of Ningbo University (No:20131220). All participants and their parents or legal guardians provided signed, informed consent. Children found to have risk levels of Vitamin E or Vitamin A were referred for further medical evaluation and appropriate interventions. Study population The study enlisted children aged 0–14 years who routinely visited community health service centers for health check-ups in Ningbo, Zhejiang, China. Participants were selected from those actively participating in the community health service centers' regular health check-up programs. This cohort was particularly relevant for assessing the prevalence and impact of Vitamin A and E statuses in children. Eligibility criteria included children present at the health service centers on the examination day, with no known chronic conditions that might affect Vitamin A or Vitamin E status. To ensure the study's validity, certain exclusions applied. Children exposed to recognized environmental contaminants were excluded to focus on the effects of Vitamins A and E. Also excluded were children on medications affecting bone metabolism and those with conditions impacting Vitamin E absorption or metabolism. This recruitment strategy aimed to reflect the general pediatric population's Vitamin A and E statuses accurately. It enabled a practical examination of the relationship between these micronutrients and health outcomes, offering insights beneficial for public health and clinical practice. Measurement of Vitamin D and Vitamin A During the physical examination, blood samples were obtained from participants, immediately stored at -20°C, and subsequently transported to a central laboratory for detailed analysis. The serum concentrations of Vitamin E and Vitamin A were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), specifically with the AB SCIEX Triple Quad 4500MD Analyzer (Sciex, part of Danaher Corporation, located in Framingham, Massachusetts, USA). To ensure the accuracy and reliability of the measurements, stringent daily quality control protocols were implemented, utilizing control materials supplied by Hehe (Hefei Hehe Medical Technology Co., Ltd., Anhui, China). The results for each vitamin were evaluated using age-specific reference intervals. For Vitamin A, levels below the lower limit of the reference interval were classified as "Deficiency," those within the interval were considered "Normal," and levels above the upper limit were labeled as "Excess." The specific reference intervals for Vitamin A are as follows: 0–6 years: 113.00-647.00 ng/mL 7–12 years: 128.00-812.00 ng/mL 13–17 years: 144.00-977.00 ng/mL ≥ 18 years: 325.00-780.00 ng/mL Similarly, Vitamin E levels were categorized based on the same criteria of "Deficiency," "Normal," and "Excess" relative to the reference intervals: 0–1 years: 1.00–5.00 µg/mL 2–12 years: 3.00–9.00 µg/mL 13–19 years: 6.00–10.00 µg/mL >19 years: 5.00–18.00 µg/mL These reference intervals were determined through extensive evaluation of serum vitamin levels in a diverse and representative sample of healthy individuals, ensuring their applicability to the general population. The laboratory's quality control measures, which include the use of control materials and regular calibration, play a crucial role in maintaining the accuracy and reliability of these reference intervals. Statistical analysis For the statistical analysis, continuous variables were represented as mean ± standard deviation (SD), while categorical variables were presented as frequencies or percentages. Intergroup differences were assessed using the Student t -test or one-way ANOVA for continuous variables, and the Chi-square ( χ² ) test or Fisher’s exact test for categorical variables, as appropriate. To investigate the relationship between Vitamin E and Vitamin A levels, smooth curve fitting was employed, followed by multivariate linear regression analyses. These analyses included both unadjusted and multivariate-adjusted models to evaluate the stability of the relationship. In Model 2, adjustments were made for age and gender, while Model 3 further accounted for seasonal variations. The findings are reported as beta coefficients ( β ) with corresponding 95% confidence intervals (CIs). To evaluate the threshold effect, two-piecewise regression models were utilized to examine the dose-response relationship between Vitamin E and Vitamin A levels, with the likelihood ratio test validating the threshold effect’s significance. All statistical analyses were executed using the R statistical software ( http://www.R-project.org , The R Foundation) and Free Statistics software (version 2.1.1, Beijing Free Clinical Medical Technology Co., Ltd.). A p -value of less than 0.05 (two-tailed) was considered statistically significant. Results Baseline Characteristics The baseline characteristics of the study participants stratified by Vitamin E status categories are presented in Table 1 . Among the total of 4,752 participants, 88 were categorized as having Vitamin E deficiency, 3,950 had normal levels, and 714 were classified as having excess Vitamin E. Significant variations were observed in the median age across the Vitamin E status categories, with the deficiency group showing a higher median age (1.5 years) compared to the normal and excess groups (0.7 and 0.6 years respectively; p < 0.001). Seasonal distribution also exhibited significant differences, with the highest proportion of participants in the summer season (35.2% in the deficiency group) and the lowest in the winter season (13.6% in the deficiency group; p < 0.001). Mean Vitamin E levels were significantly different across the categories, with the lowest mean level recorded in the deficiency group (2.4 ± 0.5 µg/mL) and the highest in the excess group (7.0 ± 1.6 µg/mL; p < 0.001). Similarly, mean Vitamin A levels showed significant variation, with the deficiency group having the lowest mean Vitamin A level (236.9 ± 60.4 ng/mL) and the excess group the highest (292.4 ± 72.3 ng/mL; p < 0.001). Gender distribution revealed a significant difference across the Vitamin E status categories ( p < 0.001), with a slightly higher proportion of males in the deficiency and normal groups (53.4% and 53.5% respectively) compared to the excess group (45.9%). Conversely, females constituted a higher proportion in the excess group (54.1%) than in the deficiency and normal groups (46.6% and 46.5% respectively). Table 1 Descriptive Characteristics of Participants by Vitamin E Status Categories Variables Total (n = 4752) Deficiency (n = 88) Normal (n = 3950) Excess (n = 714) p Gender, n (%) < 0.001 b Male 2490 (52.4) 47 (53.4) 2115 (53.5) 328 (45.9) Female 2262 (47.6) 41 (46.6) 1835 (46.5) 386 (54.1) Age, years, Median (IQR) 0.7 (0.5, 2.0) 1.5 (1.5, 3.0) 0.7 (0.5, 2.1) 0.6 (0.5, 1.0) < 0.001 a Season, n (%) < 0.001 a Spring 24 (27.3) 1059 (26.8) 241 (33.8) 1102 (26.2) Summer 31 (35.2) 1365 (34.6) 163 (22.8) 1358 (32.3) Autumn 21 (23.9) 946 (23.9) 157 (22) 1065 (25.4) Winter 12 (13.6) 580 (14.7) 153 (21.4) 676 (16.1) Vitamin E, µg/mL, Mean ± SD 4.6 ± 1.9 2.4 ± 0.5 4.2 ± 1.7 7.0 ± 1.6 < 0.001 a Vitamin A, ng/mL, Mean ± SD 259.7 ± 74.1 236.9 ± 60.4 254.3 ± 73.2 292.4 ± 72.3 < 0.001 a “a” refers to the one-way ANOVA test; “b” refers to the Chi-square test. The descriptive characteristics of participants by Vitamin A status categories are delineated in Table 2 . Among the total of 4,752 participants, 40 were identified as having Vitamin A deficiency, 4,710 had normal levels, and 2 were classified as excess. Owing to the limited number of participants in the excess group, the normal and excess groups were combined for the subsequent analysis. A statistically significant variation in gender distribution was observed across the Vitamin A status categories, with a markedly higher proportion of females in the deficiency group relative to males (70.0% females versus 30.0% males in the deficiency group, p = 0.004). Notably, there was a statistically significant difference in the median age of participants across the Vitamin A status categories ( p < 0.001). The median age was 0.5 years (IQR: 0.5–0.7) in the deficiency group and 0.7 years (IQR: 0.5–2.0) in the combined normal and excess group. In terms of seasonal distribution, a significant difference was evident, with the deficiency group exhibiting a greater proportion of participants during the summer and autumn seasons ( p = 0.006). Furthermore, Vitamin E levels were found to be significantly lower in the deficiency group when compared to the normal and excess groups ( p < 0.001). The mean Vitamin A level was considerably lower in the deficiency group at 98.4 ± 15.1 ng/mL, in contrast to the normal or excess group, where it was recorded at 261.1 ± 72.9 ng/mL, underscoring a statistically significant difference across the categories ( p < 0.001). Table 2 Descriptive Characteristics of Participants by Vitamin A Status Categories Variables Total (n = 4752) Deficiency (n = 40) Normal or Excess (n = 4712) p Gender, n (%) 0.004 b Male 2490 (52.4) 12 (30.0) 2478 (52.6) Female 2262 (47.6) 28 (70.0) 2234 (47.4) Age, years, Median(IQR) 0.7 (0.5, 2.0) 0.5 (0.5, 0.7) 0.7 (0.5, 2.0) < 0.001 a Season, n (%) 0.006 c Spring 1324 (27.9) 8 (20.0) 1316 (27.9) Summer 1559 (32.8) 16 (40.0) 1543 (32.7) Autumn 1124 (23.7) 16 (40.0) 1108 (23.5) Winter 745 (15.7) 0 (0) 745 (15.8) Vitamin E, µg/mL, Mean ± SD 4.6 ± 1.9 2.7 ± 1.3 4.6 ± 1.9 < 0.001 a Vitamin A, ng/mL, Mean ± SD 259.7 ± 74.1 98.4 ± 15.1 261.1 ± 72.9 < 0.001 a “a” refers to the Student t test; “b” refers to the Chi-square test; “c” refers to the Fisher’s exact test. Association between Vitamin D and Vitamin A Table 3 presents the regression outcomes assessing the relationship between serum vitamin E and vitamin A concentrations. Three hierarchical models were implemented with incremental covariate adjustment to evaluate this association. Model 1 demonstrated a significant positive association between serum Vitamin E and Vitamin A concentrations, with each 1 µg/mL increment in Vitamin E corresponding to a β -coefficient of 14.47 (95% CI:13.47–15.47) for Vitamin A. This association persisted in Model 2 following covariate adjustment for sex and age ( β = 14.4, 95% CI:13.35–15.46). Additional adjustment incorporating seasonal variation in Model 3 showed negligible impact on effect estimates ( β = 14.5, 95% CI:13.45–15.56). Stratified analysis by Vitamin E quintiles revealed dose-dependent increases in serum Vitamin A concentrations. Relative to the lowest Quintile (Q1: <3.15 µg/mL), covariate-adjusted models demonstrated progressive elevations: Q2 (3.15–4.18 µg/mL) β = 38.36 (95%CI:32.85–43.87); Q3 (4.18–5.82 µg/mL) β = 54.94 (49.43–60.44); Q4 (≥ 5.82 µg/mL) β = 77.94 (72.44–83.45). Significant linear trends persisted across all analytical models ( p for trend < 0.001). Gender-stratified analyses revealed statistically significant positive correlations in both sexes, demonstrating elevated β coefficients in fully adjusted models. Age-stratified evaluations maintained significance across all subgroups, with peak effect magnitudes observed in children aged 6–14 years. Significant seasonal variation was evident, with maximal β values recorded during summer and autumn meteorological periods. Table 3 Association between vitamin E and vitamin A Variable Model 1, β (95% CI) Model 2, β (95% CI) Model 3, β (95% CI) Vitamin E, µg/mL 14.47 (13.47,15.47) < 0.001 14.4 (13.35 ~ 15.46) < 0.001 14.5 (13.45 ~ 15.56) < 0.001 Quintiles Q1(<3.15µg/mL) 0 (Ref) 0 (Ref) 0 (Ref) Quintiles Q2(≥3.15, < 4.18µg/mL) 38.36 (32.85 ~ 43.87)) < 0.001 38.43 (32.89 ~ 43.97) < 0.001 38.61 (33.09 ~ 44.12) < 0.001 Quintiles Q3(≥4.18, < 5.82µg/mL) 54.94 (49.43 ~ 60.44) < 0.001 55.13 (49.45 ~ 60.82) < 0.001 55.23 (49.55 ~ 60.91) < 0.001 Quintiles Q4(≥5.82µg/mL) 77.94 (72.44 ~ 83.45) < 0.001 78.2 (72.41 ~ 83.98) < 0.001 78.7 (72.91 ~ 84.48) < 0.001 p for trend < 0.001 < 0.001 < 0.001 Gender Male 14.8 (13.42 ~ 16.17) < 0.001 14.74 (13.28 ~ 16.2) < 0.001 14.81 (13.35 ~ 16.27) < 0.001 Female 14.1 (12.64 ~ 15.57) < 0.001 14.03 (12.51 ~ 15.56) < 0.001 14.17 (12.65 ~ 15.7) < 0.001 Age group 0ཞ≤6 months 36.76 (22.22 ~ 51.30) < 0.001 47.58 (30.24 ~ 64.93) < 0.001 49.82 (28.38 ~ 71.26) < 0.001 6ཞ≤12 months 17.69 (16.13 ~ 19.26) < 0.001 17.68 (16.13 ~ 19.23) < 0.001 17.48 (15.93 ~ 19.04) < 0.001 1ཞ≤3 years 7.82 (6.01 ~ 9.63) < 0.001 7.76 (5.92 ~ 9.59) < 0.001 8.01 (6.19 ~ 9.83) < 0.001 3ཞ≤6 years 10.63 (7.92 ~ 13.34) < 0.001 10.52 (7.79 ~ 13.24) < 0.001 10.72 (7.99 ~ 13.46) < 0.001 6ཞ≤14 years 20.1 (10.74 ~ 29.45) < 0.001 22.99 (13.96 ~ 32.03) < 0.001 23.05 (13.62 ~ 32.48) < 0.001 Season Spring Summer Autumn 10.92 (9.11 ~ 12.73) < 0.001 16.49 (14.77 ~ 18.21) < 0.001 16.42 (14.29 ~ 18.54) < 0.001 10.66 (8.75 ~ 12.56) < 0.001 16.73 (14.88 ~ 18.58) < 0.001 15.97 (13.73 ~ 18.21) < 0.001 10.66 (8.75 ~ 12.56) < 0.001 16.73 (14.88 ~ 18.58) < 0.001 15.97 (13.73 ~ 18.21) < 0.001 Winter 15.19 (12.52 ~ 17.86) < 0.001 15.38 (12.64 ~ 18.12) < 0.001 15.38 (12.64 ~ 18.12) < 0.001 Model 1: No covariates were adjusted. Model 2: Gender and age were adjusted. Model 3: Gender, age and season were adjusted. Figures 1 and Table 4 showcase the findings from the analysis of the relationship between Vitamin E and Vitamin A levels, particularly emphasizing the threshold effect. Table 4 Threshold effect analysis of the relationship of Vitamin E and Vitamin A. Adjusted for gender, age and season. Vitamin E β (95% CI) p value < 3.579 µg/mL 35.829 (30.217, 41.441) < 0.001 ≥ 3.579 µg/mL 9.828 (8.250, 11.406) < 0.001 Likelihood Ratio test - < 0.001 CI, confidence interval. Adjusted for gender, age and season. In the restricted cubic spline model (Fig. 1 ), the correlation between Vitamin E levels and Vitamin A was linear ( p < 0.001). The two-piecewise regression models identified a significant threshold effect in their relationship. As shown in Table 4 , after adjusting for gender, age, and season, the threshold effect analysis indicates a critical threshold at a Vitamin E level of 3.579 µg/mL. Below this threshold, there is a robust correlation between Vitamin E and Vitamin A levels, with a beta coefficient ( β ) of 35.829 (95% CI: 30.217, 41.441). However, once Vitamin E levels reach or exceed this threshold, the beta coefficient drops substantially to 9.828 (95% CI: 8.250, 11.406), indicating a weaker association. The likelihood ratio test also confirms the significance of this threshold effect ( p < 0.001), further supporting the two-phase linear relationship between Vitamin E and Vitamin A levels. Discussion Our study offers an extensive analysis of the relationship between Vitamin E and Vitamin A levels in children aged 0–14 years, revealing a two-phase linear pattern with a critical threshold in Vitamin E levels where the correlation with Vitamin A stabilizes. This threshold is highly relevant for public health strategies aiming to enhance the status of these vitamins in children. The baseline characteristics in Table 1 show significant variations in Vitamin E and Vitamin A levels across different deficiency categories. The differences in these vitamins' mean levels by gender, age, and season highlight the impact of demographic and environmental factors on micronutrient status. The elevated mean age in the severe deficiency group and seasonal fluctuations suggest a complex interplay between Vitamin E synthesis, dietary intake, and other environmental factors that merits further exploration. Older children might have lower Vitamin E levels due to accelerated growth and increased demand for skeletal and muscular development, which could deplete body stores of Vitamin E (14,15). The observed seasonal variations align with findings that UVB radiation and dietary patterns vary with seasons, influencing Vitamin E status (16,17). Gender differences in Vitamin E levels could be influenced by variations in metabolic rates, body composition, and dietary habits. This balance is crucial as excessive intake of Vitamin E can have pro-oxidant effects, while insufficient intake leads to inadequate Vitamin E status, underscoring the need for public health strategies that optimize Vitamin E intake while avoiding excessive supplementation (18,19). Association analysis reveals a strong link between Vitamin E and Vitamin A levels, even after controlling for multiple covariates. The progressively increasing beta coefficients across the three models indicate that higher Vitamin E levels are positively correlated with higher Vitamin A levels. This relationship may be explained by several potential mechanisms. Both Vitamin E and Vitamin A are fat-soluble antioxidants that work synergistically to protect cell membranes and reduce oxidative damage (20). Their absorption, transport, and storage rely on lipid metabolic pathways, which means their levels in the body are often influenced by similar factors (21). A deficiency in either vitamin can impair antioxidant defenses, increasing the risk of cellular damage and disease (22). The positive association observed in this study may reflect a shared mechanism where both vitamins contribute to critical physiological processes such as antioxidant function and cell membrane stability. Future research should further explore these interactions to better understand their implications for health and disease prevention. Our study detected a threshold phenomenon, with a significant inflection point at 3.579 µg/mL of Vitamin E. This implies the Vitamin E-Vitamin A relationship varies with Vitamin E concentrations. When Vitamin E levels are below this point, the two vitamins' association strengthens considerably. It hints that Vitamin E might be more crucial in regulating Vitamin A levels under low - concentration conditions. Multiple biological mechanisms can clarify this. As a potent antioxidant (23), Vitamin E protects cell membranes and averts Vitamin A oxidation. Vitamin E deficiency can escalate oxidative stress, indirectly impacting Vitamin A status by changing key enzymes in Vitamin A metabolism. Vitamin E's impact on immunity is well - established (24). It modulates cytokine expression, influencing Vitamin A metabolism and retinoid signaling. In infection or inflammation, the Vitamin E-Vitamin A interaction is more vital at low Vitamin E levels. Genetic factors also matter. For instance, α - tocopherol transfer protein gene variants can alter Vitamin E metabolism (25). Genetic elements affecting Vitamin E absorption and transport can influence its levels and subsequent Vitamin A interactions (26). Vitamin E synthesis and distribution depend on dietary intake (27). In regions with sparse Vitamin E - rich food access, Vitamin E deficiency is more common, intensifying the Vitamin E-Vitamin A interaction (28). Environmental factors like cooking and food processing also affect Vitamin E and Vitamin A (29). These factors may contribute to the threshold effect by influencing the balance between Vitamin E intake and metabolic demands. The identification of a nonlinear correlation and a threshold point in children's Vitamin E levels in our study carries substantial clinical weight. This highlights the critical nature of preserving Vitamin E within an optimal bandwidth to bolster children's health, particularly among high - risk cohorts, such as older children and those with restricted access to Vitamin E - laden foods. Our data supply a definitive threshold, aiding clinical observation and intervention. This enables healthcare providers to direct Vitamin E supplementation and dietary guidance, guaranteeing children's Vitamin E levels are appropriately balanced. Public health initiatives ought to advocate for adequate Vitamin E consumption via diet while curbing the perils of over - supplementation. Personalized interventions should cater to children with Vitamin E deficiency, taking into account the interplay with Vitamin A. The threshold point represents a pivotal juncture where Vitamin E's influence on health outcomes plateaus, presenting a focal point for clinical action. This understanding can underpin targeted efforts to optimize Vitamin E status, possibly enhancing pediatric health outcomes. Our study provides novel insights into the dynamic between Vitamin E and Vitamin A levels, yet several constraints must be acknowledged. The cross - sectional nature of the study implies that data collection occurred at a solitary time point. This restricts our capacity to deduce causation or track the temporal evolution of these micronutrients. Moreover, our sample was restricted to children in Ningbo, Zhejiang, an area with unique climatic and dietary characteristics. This may circumscribe the applicability of our findings to regions with disparate climates, latitudes, or eating patterns. Lastly, despite excluding children with chronic conditions or specific medications, unmeasured confounders like genetic diversity, socioeconomic standing, or micronutrient supplementation habits might still skew the observed relationships. Future research should aim to overcome these limitations by employing longitudinal methodologies and factoring in a wider array of potential confounders. Conclusions Our research solidifies the understanding of the significant interplay between Vitamin E and Vitamin A in children, pinpointing a pivotal threshold at 3.579 µg/mL for Vitamin E, after which its linkage to Vitamin A levels stabilizes. This threshold accentuates the necessity of adequate Vitamin E levels for maintaining proper Vitamin A status, especially in vulnerable groups like older children or those with limited access to Vitamin E-rich foods. While our study lays a foundational understanding, there's a clear need for future longitudinal research. Such studies could validate our findings and delve into whether changes in Vitamin E levels can forecast Vitamin A deficiencies or other health-related issues over time. This line of inquiry has the potential to clarify the cause-and-effect relationships involved and to guide the development of more precise and effective interventions for children at risk. Our work, therefore, not only contributes to the current knowledge base but also opens avenues for more detailed and mechanistic explorations into how these essential micronutrients interact and influence each other. Declarations Ethics approval and consent to participate This study is part of a research project approved by the Ningbo University Ethics Committee. (Approval Code: NBU-2024-096). All procedures involving human participants adhered to the ethical guidelines established by the institutional and/or national research committee, as well as the 1964 Helsinki Declaration and its subsequent revisions or analogous ethical frameworks. Additionally, all study participants provided written informed consent prior to their involvement in the study. Supporting information S1 raw data Funding This study was supported by National Natural Science Foundation of China (NO. U24A20638), Ningbo Key Laboratory for the Prevention and Treatment of Embryo Original Diseases by Ningbo Science and Technology Bureau, Key Technology Breakthrough Program of 'Ningbo Sci-Tech Innovation YONGJIANG 2035 by Ningbo Science and Technology Bureau (No.2024Z222). Author Contribution WYL, QW, ZLL: Writing – original draft, JSZ, CSC: Writing – review & editing. All authors reviewed the manuscript. Acknowledgement Our heartfelt thanks go to the healthcare professionals who played a role in recruiting children for health check-ups. Their devotion and enthusiasm for pediatric welfare were key to this study's success. We especially appreciate their professional knowledge, diligent efforts, and the empathetic care they offered to participants and their families. Data Availability The dataset supporting the conclusions of this article is included within the article as additional files. Additional datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. References Lee, G., & Han, S. The Role of Vitamin E in Immunity. Nutrients. 2018; 10. https://doi.org/10.3390/nu10111614. Huang, Z., Liu, Y., Qi, G., Brand, D., & Zheng, S. Role of Vitamin A in the Immune System. 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Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2020 https://doi.org/10.1016/j.soard.2020.10.029. Shastak, Y., & Pelletier, W. Review of Liquid Vitamin A and E Formulations in Veterinary and Livestock Production: Applications and Perspectives. Veterinary Sciences. 2024; 11. https://doi.org/10.3390/vetsci11090421. Chen, G., Weiskirchen, S., & Weiskirchen, R. Vitamin A: too good to be bad?. Frontiers in Pharmacology. 2023; 14. https://doi.org/10.3389/fphar.2023.1186336. Wiseman, E., Dadon, B., & Reifen, R. The vicious cycle of vitamin a deficiency: A review. Critical Reviews in Food Science and Nutrition. 2017; 57. https://doi.org/10.1080/10408398.2016.1160362. Ungurianu, A., Zanfirescu, A., Nitulescu, G., & Margină, D. Vitamin E beyond Its Antioxidant Label. Antioxidants. 2021; 10. https://doi.org/10.3390/antiox10050634. Talib, W., Jum’AH, D., Attallah, Z., Jallad, M., Kury, L., Hadi, R., & Mahmod, A. Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action. Frontiers in Nutrition. 2024; 10. https://doi.org/10.3389/fnut.2023.1281879. Lowe, N. The global challenge of hidden hunger: perspectives from the field. Proceedings of the Nutrition Society. 2021; 80. https://doi.org/10.1017/S0029665121000902. Cui, A., Xiao, P., Fan, Z., Zeng, Y., Wang, H., & Zhuang, Y. Associations between vitamin E status and bone mineral density in children and adolescents aged 8–19 years: Evidence based on NHANES 2005–2006, 2017–2018. PLOS ONE. 2023; 18. https://doi.org/10.1371/journal.pone.0283127. Meacci, E., Chirco, A., & Garcia-Gil, M. Potential Vitamin E Signaling Mediators in Skeletal Muscle. Antioxidants. 2024; 13. https://doi.org/10.3390/antiox13111383. Grant, W., & Boucher, B. An Exploration of How Solar Radiation Affects the Seasonal Variation of Human Mortality Rates and the Seasonal Variation in Some Other Common Disorders. Nutrients. 2022; 14. https://doi.org/10.3390/nu14122519. Khanna, T., Shraim, R., Žarković, M., Van Weele, M., Van Geffen, J., & Zgaga, L. Comprehensive Analysis of Seasonal and Geographical Variation in UVB Radiation Relevant for Vitamin D Production in Europe. Nutrients. 2022; 14. https://doi.org/10.3390/nu14235189. Bi, X., Forde, C., Goh, A., & Henry, C. Basal Metabolic Rate and Body Composition Predict Habitual Food and Macronutrient Intakes: Gender Differences. Nutrients. 2019; 11. https://doi.org/10.3390/nu11112653. Szewczyk, K., Bryś, J., Brzezińska, R., & Górnicka, M. Nutritional Status of Vitamin E and Its Association with Metabolic Health in Adults. Nutrients. 2025; 17. https://doi.org/10.3390/nu17030408. 20., X., Guo, Y., Li, P., Xu, J., Gao, Y., Ren, X., Van Halm-Lutterodt, N., & Yuan, L. Association between ApoE status, circulating vitamin A and vitamin E levels with dyslipidemia in aging Chinese adults.. Archives of medical research. 2021 https://doi.org/10.1016/j.arcmed.2021.04.007. Yang, G., Wang, N., Liu, H., Si, L., & Zhao, Y. The association between umbilical cord blood fat-soluble vitamin concentrations and infant birth weight. Frontiers in Endocrinology. 2023; 14. https://doi.org/10.3389/fendo.2023.1048615. Yang, G., Wang, N., Liu, H., Si, L., & Zhao, Y. The association between umbilical cord blood fat-soluble vitamin concentrations and infant birth weight. Frontiers in Endocrinology. 2023; 14. https://doi.org/10.3389/fendo.2023.1048615. Blaner, W., Shmarakov, I., & Traber, M. Vitamin A and Vitamin E: Will the Real Antioxidant Please Stand Up?. Annual review of nutrition. 2021 https://doi.org/10.1146/annurev-nutr-082018-124228. Adly, A., Ismail, E., Ibrahim, F., Atef, M., Sayed, K., & Aly, N. A 6-month randomized controlled trial for vitamin E supplementation in pediatric patients with Gaucher disease: Effect on oxidative stress, disease severity and hepatic complications.. Journal of inherited metabolic disease. 2024 https://doi.org/10.1002/jimd.12792. Bösch, E., Spörri, J., & Scherr, J. Vitamin Metabolism and Its Dependency on Genetic Variations Among Healthy Adults: A Systematic Review for Precision Nutrition Strategies. Nutrients. 2025; 17. https://doi.org/10.3390/nu17020242. Liao, S., Omage, S., Börmel, L., Kluge, S., Schubert, M., Wallert, M., & Lorkowski, S. Vitamin E and Metabolic Health: Relevance of Interactions with Other Micronutrients. Antioxidants. 2022; 11. https://doi.org/10.3390/antiox11091785. Flory, S., Birringer, M., & Frank, J. Bioavailability and Metabolism of Vitamin E. Vitamin E in Human Health. 2019 https://doi.org/10.1007/978-3-030-05315-4_4. Scorletti, E., Creasy, K., Vujković, M., Vell, M., Zandvakili, I., Rader, D., Schneider, K., & Schneider, C. Dietary Vitamin E Intake Is Associated With a Reduced Risk of Developing Digestive Diseases and Nonalcoholic Fatty Liver Disease. The American Journal of Gastroenterology. 2022; 117. https://doi.org/10.14309/ajg.0000000000001726. Garg, M., Sharma, A., Vats, S., Tiwari, V., Kumari, A., Mishra, V., & Krishania, M. Vitamins in Cereals: A Critical Review of Content, Health Effects, Processing Losses, Bioaccessibility, Fortification, and Biofortification Strategies for Their Improvement. Frontiers in Nutrition. 2021; 8. https://doi.org/10.3389/fnut.2021.586815. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6707714","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":466438099,"identity":"1e4b278c-f7ca-4c31-8e47-7d74b2540942","order_by":0,"name":"Wenyuan Liu","email":"","orcid":"","institution":"The Affiliated Women and Children's Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Wenyuan","middleName":"","lastName":"Liu","suffix":""},{"id":466438100,"identity":"be754f6d-8c02-4e24-8231-08ebc8ac406a","order_by":1,"name":"Qiao Wang","email":"","orcid":"","institution":"Qiu'ga Central Health Clinic","correspondingAuthor":false,"prefix":"","firstName":"Qiao","middleName":"","lastName":"Wang","suffix":""},{"id":466438101,"identity":"163bf687-5811-4601-af56-7588aa650278","order_by":2,"name":"Zhuoling Li","email":"","orcid":"","institution":"The Affiliated Women and Children's Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Zhuoling","middleName":"","lastName":"Li","suffix":""},{"id":466438102,"identity":"f12605c6-2a3b-4634-932b-e63124843d37","order_by":3,"name":"Jishan Zheng","email":"","orcid":"","institution":"The Affiliated Women and Children's Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Jishan","middleName":"","lastName":"Zheng","suffix":""},{"id":466438103,"identity":"ba833ea1-b183-4086-b7de-b5e0f6f75529","order_by":4,"name":"Changshui Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqUlEQVRIiWNgGAWjYDACCTBpwyPP3kCaljQZw54DpGk5bMNwI4FIHfyzm489+PHnPA/jjATGDx9ziLHkzrF0w9622zzsPA+YJWduI0KLgUSOmTRjw20exvYENmZe4rTkf5Nm+HOOh+EA8Vpy2KQZ2A7wMJwgVovEjTQzyd62ZB7DnoPNxPmFf0byM4kff+zs5dmbD374SIwWJMDYQJr6UTAKRsEoGAW4AQD0dzHRHMVcQQAAAABJRU5ErkJggg==","orcid":"","institution":"The Affiliated Women and Children's Hospital of Ningbo University","correspondingAuthor":true,"prefix":"","firstName":"Changshui","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-05-20 12:23:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6707714/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6707714/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-22785-7","type":"published","date":"2025-11-06T15:57:25+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84218864,"identity":"25b951ba-55d2-46f7-8399-18e69c88ef1c","added_by":"auto","created_at":"2025-06-09 11:19:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":40760,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRelationship between Vitamin E and Vitamin A. \u003c/strong\u003eSolid and dashed lines represent the predicted value and 95% confidence intervals. They were adjusted for gender, age and season.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6707714/v1/03c28197481048aec020c6d4.png"},{"id":95563997,"identity":"9921cbcb-625f-4fa5-b6f3-4a34ec7afe6d","added_by":"auto","created_at":"2025-11-10 16:06:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":808951,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6707714/v1/153968b8-89f8-4d03-bc8d-ec59b4b5deab.pdf"},{"id":84218866,"identity":"18201bd8-748e-4aca-8991-17e26b289ce7","added_by":"auto","created_at":"2025-06-09 11:19:49","extension":"csv","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":101968,"visible":true,"origin":"","legend":"\u003cp\u003eS1 raw data\u003c/p\u003e","description":"","filename":"S1rawdata.csv","url":"https://assets-eu.researchsquare.com/files/rs-6707714/v1/e9c2bebf4387ff20031add65.csv"}],"financialInterests":"No competing interests reported.","formattedTitle":"Two-phase linear relationship and threshold effects between Vitamin E and Vitamin A levels in children aged 0-14 years: a cross-sectional study","fulltext":[{"header":"Background","content":"\u003cp\u003eAs critical micronutrients, vitamin A (retinoids) and vitamin E (tocopherols) demonstrate pleiotropic biological functions, particularly in immunomodulation, skeletal system homeostasis maintenance, and regulation of cellular proliferation and differentiation processes (1,2,3,4). Their deficiencies are associated with a range of health issues, particularly in children, where growth and development are most critical (5). Despite their importance, the relationship between these two vitamins and the influence of demographic, environmental, and physiological factors on their levels remain complex and not fully understood.\u003c/p\u003e \u003cp\u003eVitamin E, a potent antioxidant, is crucial for protecting cell membranes, supporting immune function, and maintaining neurological health. It is primarily obtained through diet, with vegetable oils, nuts, and green leafy vegetables being rich sources (6). Vitamin E deficiency can lead to neurological disorders, anemia, and increased susceptibility to infections (7). Vitamin A, on the other hand, is vital for vision, immune function, and reproductive health. It is obtained through dietary sources such as liver, fish oils, and dairy products, or synthesized from provitamin A carotenoids found in fruits and vegetables (8,9). Deficiency in Vitamin A is a leading cause of preventable blindness in children and can also result in increased susceptibility to infections and other health complications (10).\u003c/p\u003e \u003cp\u003eThe metabolism and function of Vitamin E and Vitamin A are closely interrelated. Both vitamins are fat-soluble and share common transport mechanisms in the body. Recent studies have suggested that there may be synergistic effects between these two vitamins, particularly in terms of their antioxidant functions and their roles in immune modulation (11,12). However, the exact nature of their interaction and the potential threshold effects in children have not been adequately explored. Understanding this relationship is crucial for developing effective public health interventions aimed at addressing micronutrient deficiencies in pediatric populations.\u003c/p\u003e \u003cp\u003eGlobally, micronutrient deficiencies are a significant public health concern, particularly in low- and middle-income countries where access to diverse diets and supplements may be limited (13). In children, these deficiencies can have long-term consequences on growth, development, and overall health outcomes. Previous research has examined the individual roles of Vitamin E and Vitamin A, but there is a paucity of studies investigating their combined effects and potential threshold interactions in children. Identifying such thresholds could have substantial implications for optimizing the status of these vitamins through targeted interventions.\u003c/p\u003e \u003cp\u003eThis cross-sectional investigation employs population-stratified sampling to elucidate the biphasic dose-response correlation between Vitamin E and Vitamin A concentrations in pediatric cohorts. We postulate a critical serum threshold beyond which retinol homeostasis demonstrates stabilization, as quantified through segmented regression modeling. The dual focus on deficiency epidemiology and micronutrient interaction dynamics aims to advance nutritional biomarker interpretation frameworks, with potential applications in: (1) refining dietary reference intake algorithms, (2) optimizing combined supplementation protocols, and (3) developing age-specific deficiency risk stratification matrices.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis cross-sectional study set out to explore the relationship between Vitamin E and Vitamin A levels in children aged 0\u0026ndash;14 years (Clinical trial number: not applicable). The sample size was determined to ensure sufficient statistical power for identifying significant associations, thereby underpinning the reliability of the results. Participant recruitment took place from January 1, 2018, to December 31, 2021. This timeframe allowed for a comprehensive capture of the participants' health status at a specific moment, facilitating an accurate analysis of Vitamin E prevalence and its relationship with Vitamin A levels. The study obtained ethical approval from the Ethics Committee of the Affiliated Women and Children\u0026rsquo;s Hospital of Ningbo University (No:20131220). All participants and their parents or legal guardians provided signed, informed consent. Children found to have risk levels of Vitamin E or Vitamin A were referred for further medical evaluation and appropriate interventions.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003eThe study enlisted children aged 0\u0026ndash;14 years who routinely visited community health service centers for health check-ups in Ningbo, Zhejiang, China. Participants were selected from those actively participating in the community health service centers' regular health check-up programs. This cohort was particularly relevant for assessing the prevalence and impact of Vitamin A and E statuses in children. Eligibility criteria included children present at the health service centers on the examination day, with no known chronic conditions that might affect Vitamin A or Vitamin E status. To ensure the study's validity, certain exclusions applied. Children exposed to recognized environmental contaminants were excluded to focus on the effects of Vitamins A and E. Also excluded were children on medications affecting bone metabolism and those with conditions impacting Vitamin E absorption or metabolism. This recruitment strategy aimed to reflect the general pediatric population's Vitamin A and E statuses accurately. It enabled a practical examination of the relationship between these micronutrients and health outcomes, offering insights beneficial for public health and clinical practice.\u003c/p\u003e\n\u003ch3\u003eMeasurement of Vitamin D and Vitamin A\u003c/h3\u003e\n\u003cp\u003eDuring the physical examination, blood samples were obtained from participants, immediately stored at -20\u0026deg;C, and subsequently transported to a central laboratory for detailed analysis. The serum concentrations of Vitamin E and Vitamin A were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), specifically with the AB SCIEX Triple Quad 4500MD Analyzer (Sciex, part of Danaher Corporation, located in Framingham, Massachusetts, USA). To ensure the accuracy and reliability of the measurements, stringent daily quality control protocols were implemented, utilizing control materials supplied by Hehe (Hefei Hehe Medical Technology Co., Ltd., Anhui, China).\u003c/p\u003e \u003cp\u003eThe results for each vitamin were evaluated using age-specific reference intervals. For Vitamin A, levels below the lower limit of the reference interval were classified as \"Deficiency,\" those within the interval were considered \"Normal,\" and levels above the upper limit were labeled as \"Excess.\" The specific reference intervals for Vitamin A are as follows:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e0\u0026ndash;6 years: 113.00-647.00 ng/mL\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e7\u0026ndash;12 years: 128.00-812.00 ng/mL\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e13\u0026ndash;17 years: 144.00-977.00 ng/mL\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026ge;\u0026thinsp;18 years: 325.00-780.00 ng/mL\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eSimilarly, Vitamin E levels were categorized based on the same criteria of \"Deficiency,\" \"Normal,\" and \"Excess\" relative to the reference intervals:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e0\u0026ndash;1 years: 1.00\u0026ndash;5.00 \u0026micro;g/mL\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e2\u0026ndash;12 years: 3.00\u0026ndash;9.00 \u0026micro;g/mL\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e13\u0026ndash;19 years: 6.00\u0026ndash;10.00 \u0026micro;g/mL\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026gt;19 years: 5.00\u0026ndash;18.00 \u0026micro;g/mL\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThese reference intervals were determined through extensive evaluation of serum vitamin levels in a diverse and representative sample of healthy individuals, ensuring their applicability to the general population. The laboratory's quality control measures, which include the use of control materials and regular calibration, play a crucial role in maintaining the accuracy and reliability of these reference intervals.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor the statistical analysis, continuous variables were represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), while categorical variables were presented as frequencies or percentages. Intergroup differences were assessed using the Student \u003cem\u003et\u003c/em\u003e-test or one-way ANOVA for continuous variables, and the Chi-square (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e) test or Fisher\u0026rsquo;s exact test for categorical variables, as appropriate. To investigate the relationship between Vitamin E and Vitamin A levels, smooth curve fitting was employed, followed by multivariate linear regression analyses. These analyses included both unadjusted and multivariate-adjusted models to evaluate the stability of the relationship. In Model 2, adjustments were made for age and gender, while Model 3 further accounted for seasonal variations. The findings are reported as beta coefficients (\u003cem\u003eβ\u003c/em\u003e) with corresponding 95% confidence intervals (CIs). To evaluate the threshold effect, two-piecewise regression models were utilized to examine the dose-response relationship between Vitamin E and Vitamin A levels, with the likelihood ratio test validating the threshold effect\u0026rsquo;s significance.\u003c/p\u003e \u003cp\u003eAll statistical analyses were executed using the R statistical software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org\u003c/span\u003e\u003cspan address=\"http://www.R-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, The R Foundation) and Free Statistics software (version 2.1.1, Beijing Free Clinical Medical Technology Co., Ltd.). A \u003cem\u003ep\u003c/em\u003e-value of less than 0.05 (two-tailed) was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Characteristics\u003c/h2\u003e \u003cp\u003eThe baseline characteristics of the study participants stratified by Vitamin E status categories are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among the total of 4,752 participants, 88 were categorized as having Vitamin E deficiency, 3,950 had normal levels, and 714 were classified as having excess Vitamin E. Significant variations were observed in the median age across the Vitamin E status categories, with the deficiency group showing a higher median age (1.5 years) compared to the normal and excess groups (0.7 and 0.6 years respectively; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Seasonal distribution also exhibited significant differences, with the highest proportion of participants in the summer season (35.2% in the deficiency group) and the lowest in the winter season (13.6% in the deficiency group; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eMean Vitamin E levels were significantly different across the categories, with the lowest mean level recorded in the deficiency group (2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 \u0026micro;g/mL) and the highest in the excess group (7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 \u0026micro;g/mL; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, mean Vitamin A levels showed significant variation, with the deficiency group having the lowest mean Vitamin A level (236.9\u0026thinsp;\u0026plusmn;\u0026thinsp;60.4 ng/mL) and the excess group the highest (292.4\u0026thinsp;\u0026plusmn;\u0026thinsp;72.3 ng/mL; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Gender distribution revealed a significant difference across the Vitamin E status categories (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with a slightly higher proportion of males in the deficiency and normal groups (53.4% and 53.5% respectively) compared to the excess group (45.9%). Conversely, females constituted a higher proportion in the excess group (54.1%) than in the deficiency and normal groups (46.6% and 46.5% respectively).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescriptive Characteristics of Participants by Vitamin E Status Categories\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;4752)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDeficiency (n\u0026thinsp;=\u0026thinsp;88)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNormal (n\u0026thinsp;=\u0026thinsp;3950)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eExcess (n\u0026thinsp;=\u0026thinsp;714)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2490 (52.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47 (53.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2115 (53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e328 (45.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2262 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1835 (46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e386 (54.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.7 (0.5, 2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.5 (1.5, 3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7 (0.5, 2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.6 (0.5, 1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeason, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpring\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1059 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e241 (33.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1102 (26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSummer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31 (35.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1365 (34.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e163 (22.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1358 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutumn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21 (23.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e946 (23.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e157 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1065 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWinter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e580 (14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e153 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e676 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin E, \u0026micro;g/mL, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin A, ng/mL, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e259.7\u0026thinsp;\u0026plusmn;\u0026thinsp;74.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e236.9\u0026thinsp;\u0026plusmn;\u0026thinsp;60.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e254.3\u0026thinsp;\u0026plusmn;\u0026thinsp;73.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e292.4\u0026thinsp;\u0026plusmn;\u0026thinsp;72.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u0026ldquo;a\u0026rdquo; refers to the one-way ANOVA test; \u0026ldquo;b\u0026rdquo; refers to the Chi-square test.\u003c/p\u003e \u003cp\u003eThe descriptive characteristics of participants by Vitamin A status categories are delineated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the total of 4,752 participants, 40 were identified as having Vitamin A deficiency, 4,710 had normal levels, and 2 were classified as excess. Owing to the limited number of participants in the excess group, the normal and excess groups were combined for the subsequent analysis. A statistically significant variation in gender distribution was observed across the Vitamin A status categories, with a markedly higher proportion of females in the deficiency group relative to males (70.0% females versus 30.0% males in the deficiency group, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). Notably, there was a statistically significant difference in the median age of participants across the Vitamin A status categories (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The median age was 0.5 years (IQR: 0.5\u0026ndash;0.7) in the deficiency group and 0.7 years (IQR: 0.5\u0026ndash;2.0) in the combined normal and excess group. In terms of seasonal distribution, a significant difference was evident, with the deficiency group exhibiting a greater proportion of participants during the summer and autumn seasons (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006). Furthermore, Vitamin E levels were found to be significantly lower in the deficiency group when compared to the normal and excess groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean Vitamin A level was considerably lower in the deficiency group at 98.4\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1 ng/mL, in contrast to the normal or excess group, where it was recorded at 261.1\u0026thinsp;\u0026plusmn;\u0026thinsp;72.9 ng/mL, underscoring a statistically significant difference across the categories (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescriptive Characteristics of Participants by Vitamin A Status Categories\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;4752)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDeficiency (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNormal or Excess (n\u0026thinsp;=\u0026thinsp;4712)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2490 (52.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2478 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2262 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2234 (47.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, Median(IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.7 (0.5, 2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.5, 0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7 (0.5, 2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeason, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpring\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1324 (27.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1316 (27.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSummer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1559 (32.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1543 (32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutumn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1124 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1108 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWinter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e745 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e745 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin E, \u0026micro;g/mL, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin A, ng/mL, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e259.7\u0026thinsp;\u0026plusmn;\u0026thinsp;74.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.4\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e261.1\u0026thinsp;\u0026plusmn;\u0026thinsp;72.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u0026ldquo;a\u0026rdquo; refers to the Student \u003cem\u003et\u003c/em\u003e test; \u0026ldquo;b\u0026rdquo; refers to the Chi-square test; \u0026ldquo;c\u0026rdquo; refers to the Fisher\u0026rsquo;s exact test.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAssociation between Vitamin D and Vitamin A\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the regression outcomes assessing the relationship between serum vitamin E and vitamin A concentrations. Three hierarchical models were implemented with incremental covariate adjustment to evaluate this association.\u003c/p\u003e \u003cp\u003eModel 1 demonstrated a significant positive association between serum Vitamin E and Vitamin A concentrations, with each 1 \u0026micro;g/mL increment in Vitamin E corresponding to a \u003cem\u003eβ\u003c/em\u003e-coefficient of 14.47 (95% CI:13.47\u0026ndash;15.47) for Vitamin A. This association persisted in Model 2 following covariate adjustment for sex and age (\u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;14.4, 95% CI:13.35\u0026ndash;15.46). Additional adjustment incorporating seasonal variation in Model 3 showed negligible impact on effect estimates (\u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;14.5, 95% CI:13.45\u0026ndash;15.56).\u003c/p\u003e \u003cp\u003eStratified analysis by Vitamin E quintiles revealed dose-dependent increases in serum Vitamin A concentrations. Relative to the lowest Quintile (Q1: \u0026lt;3.15 \u0026micro;g/mL), covariate-adjusted models demonstrated progressive elevations: Q2 (3.15\u0026ndash;4.18 \u0026micro;g/mL) \u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38.36 (95%CI:32.85\u0026ndash;43.87); Q3 (4.18\u0026ndash;5.82 \u0026micro;g/mL) \u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;54.94 (49.43\u0026ndash;60.44); Q4 (\u0026ge;\u0026thinsp;5.82 \u0026micro;g/mL) \u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;77.94 (72.44\u0026ndash;83.45). Significant linear trends persisted across all analytical models (\u003cem\u003ep\u003c/em\u003e for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eGender-stratified analyses revealed statistically significant positive correlations in both sexes, demonstrating elevated \u003cem\u003eβ\u003c/em\u003e coefficients in fully adjusted models. Age-stratified evaluations maintained significance across all subgroups, with peak effect magnitudes observed in children aged 6\u0026ndash;14 years. Significant seasonal variation was evident, with maximal \u003cem\u003eβ\u003c/em\u003e values recorded during summer and autumn meteorological periods.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between vitamin E and vitamin A\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 1, \u003cem\u003eβ\u003c/em\u003e (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel 2, \u003cem\u003eβ\u003c/em\u003e (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel 3, \u003cem\u003eβ\u003c/em\u003e (95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin E, \u0026micro;g/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.47 (13.47,15.47)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.4 (13.35\u0026thinsp;~\u0026thinsp;15.46)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.5 (13.45\u0026thinsp;~\u0026thinsp;15.56)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuintiles Q1(\u0026lt;3.15\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (Ref)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (Ref)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (Ref)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuintiles Q2(\u0026ge;3.15, \u0026lt;\u0026thinsp;4.18\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.36 (32.85\u0026thinsp;~\u0026thinsp;43.87))\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.43 (32.89\u0026thinsp;~\u0026thinsp;43.97)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.61 (33.09\u0026thinsp;~\u0026thinsp;44.12)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuintiles Q3(\u0026ge;4.18, \u0026lt;\u0026thinsp;5.82\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.94 (49.43\u0026thinsp;~\u0026thinsp;60.44)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.13 (49.45\u0026thinsp;~\u0026thinsp;60.82)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.23 (49.55\u0026thinsp;~\u0026thinsp;60.91)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuintiles Q4(\u0026ge;5.82\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.94 (72.44\u0026thinsp;~\u0026thinsp;83.45)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.2 (72.41\u0026thinsp;~\u0026thinsp;83.98)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.7 (72.91\u0026thinsp;~\u0026thinsp;84.48)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e for trend\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.8 (13.42\u0026thinsp;~\u0026thinsp;16.17)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.74 (13.28\u0026thinsp;~\u0026thinsp;16.2)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.81 (13.35\u0026thinsp;~\u0026thinsp;16.27)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.1 (12.64\u0026thinsp;~\u0026thinsp;15.57)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.03 (12.51\u0026thinsp;~\u0026thinsp;15.56)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.17 (12.65\u0026thinsp;~\u0026thinsp;15.7)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0ཞ\u0026le;6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.76 (22.22\u0026thinsp;~\u0026thinsp;51.30)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.58 (30.24\u0026thinsp;~\u0026thinsp;64.93)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.82 (28.38\u0026thinsp;~\u0026thinsp;71.26)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6ཞ\u0026le;12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.69 (16.13\u0026thinsp;~\u0026thinsp;19.26)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.68 (16.13\u0026thinsp;~\u0026thinsp;19.23)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.48 (15.93\u0026thinsp;~\u0026thinsp;19.04)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1ཞ\u0026le;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.82 (6.01\u0026thinsp;~\u0026thinsp;9.63)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.76 (5.92\u0026thinsp;~\u0026thinsp;9.59)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.01 (6.19\u0026thinsp;~\u0026thinsp;9.83)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3ཞ\u0026le;6 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.63 (7.92\u0026thinsp;~\u0026thinsp;13.34)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.52 (7.79\u0026thinsp;~\u0026thinsp;13.24)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.72 (7.99\u0026thinsp;~\u0026thinsp;13.46)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6ཞ\u0026le;14 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.1 (10.74\u0026thinsp;~\u0026thinsp;29.45)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.99 (13.96\u0026thinsp;~\u0026thinsp;32.03)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.05 (13.62\u0026thinsp;~\u0026thinsp;32.48)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeason\u003c/p\u003e \u003cp\u003eSpring\u003c/p\u003e \u003cp\u003eSummer\u003c/p\u003e \u003cp\u003eAutumn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.92 (9.11\u0026thinsp;~\u0026thinsp;12.73)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e16.49 (14.77\u0026thinsp;~\u0026thinsp;18.21)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e16.42 (14.29\u0026thinsp;~\u0026thinsp;18.54)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.66 (8.75\u0026thinsp;~\u0026thinsp;12.56)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e16.73 (14.88\u0026thinsp;~\u0026thinsp;18.58)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e15.97 (13.73\u0026thinsp;~\u0026thinsp;18.21)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.66 (8.75\u0026thinsp;~\u0026thinsp;12.56)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e16.73 (14.88\u0026thinsp;~\u0026thinsp;18.58)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e15.97 (13.73\u0026thinsp;~\u0026thinsp;18.21)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWinter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.19 (12.52\u0026thinsp;~\u0026thinsp;17.86)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.38 (12.64\u0026thinsp;~\u0026thinsp;18.12)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.38 (12.64\u0026thinsp;~\u0026thinsp;18.12)\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eModel 1: No covariates were adjusted.\u003c/p\u003e \u003cp\u003eModel 2: Gender and age were adjusted.\u003c/p\u003e \u003cp\u003eModel 3: Gender, age and season were adjusted.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigures 1 and Table 4 showcase the findings from the analysis of the relationship between Vitamin E and Vitamin A levels, particularly emphasizing the threshold effect.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThreshold effect analysis of the relationship of Vitamin E and Vitamin A. Adjusted for gender, age and season.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin E\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eβ\u003c/em\u003e (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;3.579 \u0026micro;g/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.829 (30.217, 41.441)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3.579 \u0026micro;g/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.828 (8.250, 11.406)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLikelihood Ratio test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCI, confidence interval. Adjusted for gender, age and season.\u003c/p\u003e \u003cp\u003eIn the restricted cubic spline model (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), the correlation between Vitamin E levels and Vitamin A was linear (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The two-piecewise regression models identified a significant threshold effect in their relationship. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, after adjusting for gender, age, and season, the threshold effect analysis indicates a critical threshold at a Vitamin E level of 3.579 \u0026micro;g/mL. Below this threshold, there is a robust correlation between Vitamin E and Vitamin A levels, with a beta coefficient (\u003cem\u003eβ\u003c/em\u003e) of 35.829 (95% CI: 30.217, 41.441). However, once Vitamin E levels reach or exceed this threshold, the beta coefficient drops substantially to 9.828 (95% CI: 8.250, 11.406), indicating a weaker association. The likelihood ratio test also confirms the significance of this threshold effect (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), further supporting the two-phase linear relationship between Vitamin E and Vitamin A levels.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study offers an extensive analysis of the relationship between Vitamin E and Vitamin A levels in children aged 0\u0026ndash;14 years, revealing a two-phase linear pattern with a critical threshold in Vitamin E levels where the correlation with Vitamin A stabilizes. This threshold is highly relevant for public health strategies aiming to enhance the status of these vitamins in children. The baseline characteristics in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e show significant variations in Vitamin E and Vitamin A levels across different deficiency categories. The differences in these vitamins' mean levels by gender, age, and season highlight the impact of demographic and environmental factors on micronutrient status.\u003c/p\u003e \u003cp\u003eThe elevated mean age in the severe deficiency group and seasonal fluctuations suggest a complex interplay between Vitamin E synthesis, dietary intake, and other environmental factors that merits further exploration. Older children might have lower Vitamin E levels due to accelerated growth and increased demand for skeletal and muscular development, which could deplete body stores of Vitamin E (14,15). The observed seasonal variations align with findings that UVB radiation and dietary patterns vary with seasons, influencing Vitamin E status (16,17). Gender differences in Vitamin E levels could be influenced by variations in metabolic rates, body composition, and dietary habits. This balance is crucial as excessive intake of Vitamin E can have pro-oxidant effects, while insufficient intake leads to inadequate Vitamin E status, underscoring the need for public health strategies that optimize Vitamin E intake while avoiding excessive supplementation (18,19).\u003c/p\u003e \u003cp\u003eAssociation analysis reveals a strong link between Vitamin E and Vitamin A levels, even after controlling for multiple covariates. The progressively increasing beta coefficients across the three models indicate that higher Vitamin E levels are positively correlated with higher Vitamin A levels. This relationship may be explained by several potential mechanisms. Both Vitamin E and Vitamin A are fat-soluble antioxidants that work synergistically to protect cell membranes and reduce oxidative damage (20). Their absorption, transport, and storage rely on lipid metabolic pathways, which means their levels in the body are often influenced by similar factors (21). A deficiency in either vitamin can impair antioxidant defenses, increasing the risk of cellular damage and disease (22). The positive association observed in this study may reflect a shared mechanism where both vitamins contribute to critical physiological processes such as antioxidant function and cell membrane stability. Future research should further explore these interactions to better understand their implications for health and disease prevention.\u003c/p\u003e \u003cp\u003eOur study detected a threshold phenomenon, with a significant inflection point at 3.579 \u0026micro;g/mL of Vitamin E. This implies the Vitamin E-Vitamin A relationship varies with Vitamin E concentrations. When Vitamin E levels are below this point, the two vitamins' association strengthens considerably. It hints that Vitamin E might be more crucial in regulating Vitamin A levels under low - concentration conditions.\u003c/p\u003e \u003cp\u003eMultiple biological mechanisms can clarify this. As a potent antioxidant (23), Vitamin E protects cell membranes and averts Vitamin A oxidation. Vitamin E deficiency can escalate oxidative stress, indirectly impacting Vitamin A status by changing key enzymes in Vitamin A metabolism. Vitamin E's impact on immunity is well - established (24). It modulates cytokine expression, influencing Vitamin A metabolism and retinoid signaling. In infection or inflammation, the Vitamin E-Vitamin A interaction is more vital at low Vitamin E levels.\u003c/p\u003e \u003cp\u003eGenetic factors also matter. For instance, α - tocopherol transfer protein gene variants can alter Vitamin E metabolism (25). Genetic elements affecting Vitamin E absorption and transport can influence its levels and subsequent Vitamin A interactions (26). Vitamin E synthesis and distribution depend on dietary intake (27). In regions with sparse Vitamin E - rich food access, Vitamin E deficiency is more common, intensifying the Vitamin E-Vitamin A interaction (28). Environmental factors like cooking and food processing also affect Vitamin E and Vitamin A (29). These factors may contribute to the threshold effect by influencing the balance between Vitamin E intake and metabolic demands.\u003c/p\u003e \u003cp\u003eThe identification of a nonlinear correlation and a threshold point in children's Vitamin E levels in our study carries substantial clinical weight. This highlights the critical nature of preserving Vitamin E within an optimal bandwidth to bolster children's health, particularly among high - risk cohorts, such as older children and those with restricted access to Vitamin E - laden foods. Our data supply a definitive threshold, aiding clinical observation and intervention. This enables healthcare providers to direct Vitamin E supplementation and dietary guidance, guaranteeing children's Vitamin E levels are appropriately balanced. Public health initiatives ought to advocate for adequate Vitamin E consumption via diet while curbing the perils of over - supplementation. Personalized interventions should cater to children with Vitamin E deficiency, taking into account the interplay with Vitamin A. The threshold point represents a pivotal juncture where Vitamin E's influence on health outcomes plateaus, presenting a focal point for clinical action. This understanding can underpin targeted efforts to optimize Vitamin E status, possibly enhancing pediatric health outcomes.\u003c/p\u003e \u003cp\u003eOur study provides novel insights into the dynamic between Vitamin E and Vitamin A levels, yet several constraints must be acknowledged. The cross - sectional nature of the study implies that data collection occurred at a solitary time point. This restricts our capacity to deduce causation or track the temporal evolution of these micronutrients. Moreover, our sample was restricted to children in Ningbo, Zhejiang, an area with unique climatic and dietary characteristics. This may circumscribe the applicability of our findings to regions with disparate climates, latitudes, or eating patterns. Lastly, despite excluding children with chronic conditions or specific medications, unmeasured confounders like genetic diversity, socioeconomic standing, or micronutrient supplementation habits might still skew the observed relationships. Future research should aim to overcome these limitations by employing longitudinal methodologies and factoring in a wider array of potential confounders.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur research solidifies the understanding of the significant interplay between Vitamin E and Vitamin A in children, pinpointing a pivotal threshold at 3.579 \u0026micro;g/mL for Vitamin E, after which its linkage to Vitamin A levels stabilizes. This threshold accentuates the necessity of adequate Vitamin E levels for maintaining proper Vitamin A status, especially in vulnerable groups like older children or those with limited access to Vitamin E-rich foods. While our study lays a foundational understanding, there's a clear need for future longitudinal research. Such studies could validate our findings and delve into whether changes in Vitamin E levels can forecast Vitamin A deficiencies or other health-related issues over time. This line of inquiry has the potential to clarify the cause-and-effect relationships involved and to guide the development of more precise and effective interventions for children at risk. Our work, therefore, not only contributes to the current knowledge base but also opens avenues for more detailed and mechanistic explorations into how these essential micronutrients interact and influence each other.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is part of a research project approved by the Ningbo University Ethics Committee. (Approval Code: NBU-2024-096). All procedures involving human participants adhered to the ethical guidelines established by the institutional and/or national research committee, as well as the 1964 Helsinki Declaration and its subsequent revisions or analogous ethical frameworks. Additionally, all study participants provided written informed consent prior to their involvement in the study.\u003c/p\u003e\n\u003ch2\u003eSupporting information\u003c/h2\u003e\n\u003cp\u003eS1 raw data\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis study was supported by National Natural Science Foundation of China (NO. U24A20638),\u003c/p\u003e\n\u003cp\u003eNingbo Key Laboratory for the Prevention and Treatment of Embryo Original Diseases by Ningbo Science and Technology Bureau, Key Technology Breakthrough Program of \u0026apos;Ningbo Sci-Tech Innovation YONGJIANG 2035 by Ningbo Science and Technology Bureau (No.2024Z222).\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eWYL, QW, ZLL: Writing \u0026ndash; original draft, JSZ, CSC: Writing \u0026ndash; review \u0026amp; editing. All authors reviewed the manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eOur heartfelt thanks go to the healthcare professionals who played a role in recruiting children for health check-ups. Their devotion and enthusiasm for pediatric welfare were key to this study\u0026apos;s success. We especially appreciate their professional knowledge, diligent efforts, and the empathetic care they offered to participants and their families.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe dataset supporting the conclusions of this article is included within the article as additional files. Additional datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee, G., \u0026amp; Han, S. The Role of Vitamin E in Immunity. \u003cem\u003eNutrients.\u003c/em\u003e 2018; 10. https://doi.org/10.3390/nu10111614.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang, Z., Liu, Y., Qi, G., Brand, D., \u0026amp; Zheng, S. Role of Vitamin A in the Immune System. \u003cem\u003eJournal of Clinical Medicine.\u003c/em\u003e 2018; 7. https://doi.org/10.3390/jcm7090258.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewis, E., Meydani, S., \u0026amp; Wu, D. Regulatory role of vitamin E in the immune system and inflammation. \u003cem\u003eIUBMB Life.\u003c/em\u003e 2018; 71. https://doi.org/10.1002/iub.1976.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYee, M., Chin, K., Ima-Nirwana, S., \u0026amp; Wong, S. 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Basal Metabolic Rate and Body Composition Predict Habitual Food and Macronutrient Intakes: Gender Differences. \u003cem\u003eNutrients.\u003c/em\u003e 2019; 11. https://doi.org/10.3390/nu11112653.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzewczyk, K., Bryś, J., Brzezińska, R., \u0026amp; G\u0026oacute;rnicka, M. Nutritional Status of Vitamin E and Its Association with Metabolic Health in Adults. \u003cem\u003eNutrients.\u003c/em\u003e 2025; 17. https://doi.org/10.3390/nu17030408.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e20., X., Guo, Y., Li, P., Xu, J., Gao, Y., Ren, X., Van Halm-Lutterodt, N., \u0026amp; Yuan, L. Association between ApoE status, circulating vitamin A and vitamin E levels with dyslipidemia in aging Chinese adults.. \u003cem\u003eArchives of medical research.\u003c/em\u003e 2021 https://doi.org/10.1016/j.arcmed.2021.04.007.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang, G., Wang, N., Liu, H., Si, L., \u0026amp; Zhao, Y. The association between umbilical cord blood fat-soluble vitamin concentrations and infant birth weight. \u003cem\u003eFrontiers in Endocrinology.\u003c/em\u003e 2023; 14. https://doi.org/10.3389/fendo.2023.1048615.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang, G., Wang, N., Liu, H., Si, L., \u0026amp; Zhao, Y. 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A 6-month randomized controlled trial for vitamin E supplementation in pediatric patients with Gaucher disease: Effect on oxidative stress, disease severity and hepatic complications.. \u003cem\u003eJournal of inherited metabolic disease.\u003c/em\u003e 2024 https://doi.org/10.1002/jimd.12792.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026ouml;sch, E., Sp\u0026ouml;rri, J., \u0026amp; Scherr, J. Vitamin Metabolism and Its Dependency on Genetic Variations Among Healthy Adults: A Systematic Review for Precision Nutrition Strategies. \u003cem\u003eNutrients.\u003c/em\u003e 2025; 17. https://doi.org/10.3390/nu17020242.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiao, S., Omage, S., B\u0026ouml;rmel, L., Kluge, S., Schubert, M., Wallert, M., \u0026amp; Lorkowski, S. Vitamin E and Metabolic Health: Relevance of Interactions with Other Micronutrients. \u003cem\u003eAntioxidants.\u003c/em\u003e 2022; 11. https://doi.org/10.3390/antiox11091785.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlory, S., Birringer, M., \u0026amp; Frank, J. Bioavailability and Metabolism of Vitamin E. \u003cem\u003eVitamin E in Human Health.\u003c/em\u003e 2019 https://doi.org/10.1007/978-3-030-05315-4_4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScorletti, E., Creasy, K., Vujković, M., Vell, M., Zandvakili, I., Rader, D., Schneider, K., \u0026amp; Schneider, C. Dietary Vitamin E Intake Is Associated With a Reduced Risk of Developing Digestive Diseases and Nonalcoholic Fatty Liver Disease. \u003cem\u003eThe American Journal of Gastroenterology.\u003c/em\u003e 2022; 117. https://doi.org/10.14309/ajg.0000000000001726.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarg, M., Sharma, A., Vats, S., Tiwari, V., Kumari, A., Mishra, V., \u0026amp; Krishania, M. Vitamins in Cereals: A Critical Review of Content, Health Effects, Processing Losses, Bioaccessibility, Fortification, and Biofortification Strategies for Their Improvement. \u003cem\u003eFrontiers in Nutrition.\u003c/em\u003e 2021; 8. https://doi.org/10.3389/fnut.2021.586815.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Vitamin E, Vitamin A, Children, Micronutrients, Threshold Effect, Public Health Intervention","lastPublishedDoi":"10.21203/rs.3.rs-6707714/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6707714/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eVitamins E and A are essential fat-soluble micronutrients critical for immune regulation, bone metabolism, and cellular homeostasis. Current evidence highlights significant gaps in understanding their interdependent relationships and the modulatory effects of age, environmental exposures, and physiological status on their systemic bioavailability.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo investigate the relationship between Vitamin E and Vitamin A levels in children aged 0\u0026ndash;14 years and identify any critical thresholds.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis cross-sectional study was conducted from 2018 to 2021 in Ningbo, Zhejiang, China. It involved children aged 0\u0026ndash;14 years who attended community health service centers for routine health check-ups. To evaluate the relationship between serum Vitamin E and Vitamin A levels, we performed a multivariate linear regression analysis. Furthermore, a smooth curve fitting approach was employed to investigate the dose-response relationship between Vitamin E and Vitamin A.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included a total of 4,752 participants. Significant variations in baseline Vitamin E and Vitamin A levels were observed across different deficiency categories. The mean Vitamin E level was lowest in the deficiency group (2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 \u0026micro;g/mL) and highest in the excess group (7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 \u0026micro;g/mL). Similarly, the mean Vitamin A level was lowest in the deficiency group (236.9\u0026thinsp;\u0026plusmn;\u0026thinsp;60.4 ng/mL) and highest in the excess group (292.4\u0026thinsp;\u0026plusmn;\u0026thinsp;72.3 ng/mL). A two-phase linear relationship was identified, with a significant threshold effect at a Vitamin E level of 3.579 \u0026micro;g/mL. Below this threshold, the association between Vitamin E and Vitamin A was robust (\u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;35.829, 95% CI: 30.217, 41.441), while above the threshold, the association weakened significantly (\u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9.828, 95% CI: 8.250, 11.406). The likelihood ratio test confirmed the significance of this threshold effect (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe study identified a significant threshold at 3.579 \u0026micro;g/mL for Vitamin E, beyond which the association with Vitamin A levels stabilizes. This threshold highlights the importance of maintaining optimal Vitamin E levels to support Vitamin A status, particularly in high-risk groups such as older children and those with limited access to Vitamin E-rich foods. Future longitudinal studies are needed to further validate these findings and explore their implications for public health interventions.\u003c/p\u003e","manuscriptTitle":"Two-phase linear relationship and threshold effects between Vitamin E and Vitamin A levels in children aged 0-14 years: a cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-09 11:19:44","doi":"10.21203/rs.3.rs-6707714/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-07T05:05:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-05T02:12:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"166150799734613597635136837497420922040","date":"2025-07-04T06:25:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-03T19:08:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"315920192559749927223263892243186588940","date":"2025-07-03T18:38:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181891635444813426782160144442164151042","date":"2025-06-10T07:50:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"238908729452045197886170566198697664203","date":"2025-06-08T06:39:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-03T05:33:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-03T05:27:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-03T04:56:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-02T05:03:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-20T12:08:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7dc93df6-adcc-4631-a15b-a9089c266d33","owner":[],"postedDate":"June 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":49521786,"name":"Health sciences/Diseases"},{"id":49521787,"name":"Health sciences/Health care"}],"tags":[],"updatedAt":"2025-11-10T16:00:30+00:00","versionOfRecord":{"articleIdentity":"rs-6707714","link":"https://doi.org/10.1038/s41598-025-22785-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-11-06 15:57:25","publishedOnDateReadable":"November 6th, 2025"},"versionCreatedAt":"2025-06-09 11:19:44","video":"","vorDoi":"10.1038/s41598-025-22785-7","vorDoiUrl":"https://doi.org/10.1038/s41598-025-22785-7","workflowStages":[]},"version":"v1","identity":"rs-6707714","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6707714","identity":"rs-6707714","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}