Association between Dietary Choline Intake, Renal Function, and Hyperuricemia in Chinese Children and Adolescents

1. Core Background and Objectives of the Study

Hyperuricemia (HUA) is characterized by elevated serum uric acid levels. It serves as a major risk factor for gout and is also associated with hypertension, type 2 diabetes, and cardiovascular impairment. In recent years, the prevalence of HUA has increased significantly among children and adolescents worldwide. Studies conducted in China, the United States, and some European countries have reported that the prevalence of HUA in this population ranges from 0.6% to 50.4%. Dietary nutrition management is a key modifiable factor for reducing the risk of HUA. Previous animal studies have indicated that dietary choline supplementation can lower uric acid levels; however, evidence from human studies—particularly among children and adolescents—remains limited. The association between dietary choline intake and HUA, as well as the role of renal function in this relationship, has not been clearly established in the pediatric and adolescent population. Therefore, this study aimed to investigate the association between dietary choline intake and HUA in Chinese children and adolescents aged 6–17 years, and to explore the mediating role of renal function (using estimated glomerular filtration rate, eGFR, as an indicator) in this relationship. Additionally, the effects of different choline subtypes (e.g., phosphatidylcholine, betaine) were examined.

2. Key Data and Research Findings

2.1 Basic Characteristics of Participants

A total of 10,749 children and adolescents aged 6–17 years were included in the final analysis (after excluding individuals with missing serum uric acid data, unreasonable energy intake, and abnormal height or serum creatinine levels). Among the participants, 65.7% were female and 85.9% were of Han ethnicity. A total of 3,398 participants (31.6%) were diagnosed with HUA, with a significantly higher prevalence in boys (36.3%) than in girls (29.2%). Comparisons between the normal group and the HUA group revealed that participants in the HUA group were more likely to have smoking habits, a history of alcohol consumption or current alcohol intake, and a higher intake of sugar-sweetened beverages. They also had higher proportions of family history of diabetes, overweight/obesity, and hypertriglyceridemia. In terms of dietary choline intake, the average total choline intake of the participants was 232.2 (142.1) mg/day, and the average betaine intake was 120.8 (116.5) mg/day. The average intakes of different choline subtypes were as follows: phosphatidylcholine (147.4 [116.5] mg/day), sphingomyelin (12.0 [8.7] mg/day), free choline (46.6 [29.1] mg/day), glycerophosphorylcholine (21.2 [14.9] mg/day), and phosphorylcholine (6.3 [5.2] mg/day).

2.2 Association between Dietary Choline Intake and Hyperuricemia

The study clearly demonstrated a negative dose-dependent relationship between dietary choline intake and HUA. After adjusting for all potential confounding factors (including gender, age, ethnicity, lifestyle habits, dietary structure, and chronic diseases), participants in the highest quartile of total choline intake (Q4, 357.92 mg/day) had a significantly reduced risk of HUA compared with those in the lowest quartile (Q1, 117.02 mg/day), with an odds ratio (OR) of 0.75. For each one-quartile increase in total choline intake, the risk of HUA decreased by 8%. Participants in the highest quartile of phosphatidylcholine intake (Q4, 207.58 mg/day) had a 25% lower risk of HUA (OR = 0.75) compared with those in the lowest quartile (Q1, 34.80 mg/day). Similarly, participants in the highest quartile of betaine intake (Q4, 282.37 mg/day) had a 25% lower risk of HUA (OR = 0.75) than those in the lowest quartile (Q1, 29.84 mg/day).

Figure 1  Association between energy-adjusted choline intake and hyperuricemia using a multiple-adjusted restricted cubic spline model

When choline was classified into lipid-soluble (phosphatidylcholine + sphingomyelin) and water-soluble (free choline + glycerophosphorylcholine + phosphorylcholine) subtypes, lipid-soluble choline was significantly associated with a reduced risk of HUA, whereas no significant association was observed for water-soluble choline. After adjusting for confounding factors, participants in the highest quartile of lipid-soluble choline intake (Q4, 222.74 mg/day) had a lower risk of HUA (OR = 0.76) compared with those in the lowest quartile (Q1, 39.11 mg/day). For each one-quartile increase in lipid-soluble choline intake, the risk of HUA decreased by 9%.

Figure 2 Odds ratios (95% CIs) of residual energy-adjusted choline intake from lipid- and water-soluble sources with hyperuricemia

Linear Association with Serum Uric Acid Levels

Multiple linear regression analysis further confirmed that after controlling for all confounding factors, the intakes of total choline, betaine, phosphatidylcholine, and sphingomyelin were significantly negatively correlated with serum uric acid levels—indicating that higher intake of these choline subtypes was associated with lower serum uric acid levels.

2.3 Mediating Role of Renal Function (eGFR)

Mediation effect analysis showed that the estimated glomerular filtration rate (eGFR) played a key mediating role in the association between dietary choline intake and HUA, with a mediation proportion ranging from 10.60% to 14.58%. The specific results were as follows: In the association between total choline and HUA, the mediation proportion of eGFR was 11.06%. In the association between betaine and HUA, the mediation proportion was the highest, reaching 14.58%. In the effects of phosphatidylcholine and lipid-soluble choline on HUA, the mediation proportions of eGFR were 10.60% and 10.57%, respectively. All these mediation effects were statistically significant, confirming that eGFR played an important mediating role in the relationship between dietary choline intake and HUA.

Figure 3 Mediation effect analysis of eGFR in the association between residual energy-adjusted choline intake and hyperuricemia

2.4 Sensitivity and Subgroup Analyses for Validation

To ensure the robustness of the results, multiple sensitivity analyses were conducted (e.g., validation using food frequency questionnaire data, analysis of energy-unadjusted choline intake, and exclusion of imputed data). The results showed that the negative associations of total choline, phosphatidylcholine, and betaine with HUA, as well as the mediating role of eGFR, remained stable. When using food frequency questionnaire data, only the negative correlation between betaine and HUA and the mediating role of eGFR were observed. In addition, the E-values for total choline, phosphatidylcholine, and betaine intake were all 2.00 (corresponding to 1.46, 1.50, and 1.32, respectively), indicating a very low possibility of unmeasured confounding factors with effects stronger than those of choline—further supporting the reliability of the study results. Furthermore, after stratification by age (6–11 years and 12–17 years) and gender, the association between energy-adjusted choline intake and HUA was consistent with the main analysis. This indicated that the association was valid across different age groups and genders of children and adolescents, with no significant subgroup differences.

3. Core Discussion and Significance

3.1 Association between Methylation Cycle and Purine Metabolism

Choline and betaine are key participants in the methylation cycle. Betaine provides methyl groups for the conversion of homocysteine to methionine, and the methylation cycle is closely linked to purine metabolism—given that uric acid is the end product of purine metabolism. Disruption of the methylation process may lead to abnormal purine catabolism, thereby increasing uric acid production. Conversely, adequate choline intake can maintain the stability of the methylation cycle, indirectly reducing uric acid production.

3.2 Oxidative Stress and Renal Function Protection

Choline is a precursor of phosphatidylcholine, an important component of cell membranes. Sufficient choline intake can maintain the integrity of cell membranes and reduce oxidative stress damage. Oxidative stress may not only directly affect purine metabolism and increase uric acid production but also impair renal function. Impaired renal function leads to reduced uric acid excretion (approximately 75% of uric acid is excreted through the kidneys), ultimately causing HUA. Therefore, choline can protect renal function by alleviating oxidative stress, thereby promoting uric acid excretion and reducing the risk of HUA.

3.3 Significance of the Mediating Role of eGFR

As a core indicator of renal function, the mediation proportion of eGFR (10.60%–14.58%) suggests that approximately 10%–15% of the preventive effect of dietary choline intake on HUA is achieved by improving glomerular filtration function. This further confirms the mechanism pathway: choline → improved renal function → enhanced uric acid excretion → reduced risk of HUA, providing a clear mechanistic basis for understanding the association between dietary choline intake and HUA.

4. Innovation and Value of the Study

Previous studies on choline and uric acid have mostly focused on animal models (e.g., broilers, dogs), with few human studies—especially among children and adolescents. This study is the first large-scale cross-sectional study conducted in Chinese children and adolescents aged 6–17 years to verify the negative association between dietary choline and HUA and the mediating role of renal function, providing key epidemiological evidence in this field. Additionally, this study is the first to systematically analyze the effects of different choline subtypes (total choline, phosphatidylcholine, betaine, lipid-soluble/water-soluble choline), and found that phosphatidylcholine, betaine, and lipid-soluble choline have more significant protective effects. This provides a basis for formulating targeted dietary recommendations and avoids the limitation of  studies that only focused on total choline.

Figure 4 Role of renal function in the association between dietary choline intake and hyperuricemia in Chinese children and adolescents

5. Practical Guidance and Future Directions

Based on the study results, it is recommended that children and adolescents increase their intake of choline-rich foods—especially those rich in phosphatidylcholine and betaine, such as eggs (egg yolks are an excellent source of phosphatidylcholine), legumes, and whole grains. Adjusting daily dietary habits can help control uric acid levels and reduce the risk of HUA. This study has limitations: it cannot fully confirm the causal relationship and temporal sequence between choline intake and HUA; moreover, data were only collected from several provinces in China, which may not fully represent the situation of all Chinese children and adolescents. Future studies should include prospective cohort studies to verify the causal relationship and intervention studies (e.g., choline supplement intervention) to further clarify the specific role of choline in the prevention and management of HUA in children and adolescents.

6. Study Conclusions

Among Chinese children and adolescents aged 6–17 years, moderate to high dietary choline intake (181.20–357.92 mg/day)—especially phosphatidylcholine (120.22–207.58 mg/day) and betaine (189.24–282.37 mg/day)—can reduce the risk of HUA by improving glomerular filtration function. Lipid-soluble choline (phosphatidylcholine + sphingomyelin) has a significant protective effect, while water-soluble choline has no obvious association. This study provides strong evidence for the dietary prevention and management of HUA in children and adolescents and has important guiding value for public health practice.

References：Li C, Li J, Diao Z, et al. Associations of dietary choline intake and kidney function with hyperuricemia in Chinese children and adolescents: a cross-sectional study[J]. EClinicalMedicine, 2024, 79: 103012.