Research Article

A Cross-Sectional Study of the Association of Serum Uric Acid Levels and Sarcopenia using the China Health and Retirement Longitudinal Study (CHARLS)

DOI:

10.3791/68961

⸱

September 26th, 2025

 ,  ,  ,  ,  ,  ,  , 
1Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, 2Department of General Practice, The First Affiliated Hospital of Chongqing Medical University

In This Article

Summary

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The study addresses a critical knowledge gap regarding the relationship between serum uric acid (UA) levels and sarcopenia, particularly in the Chinese population, where such an association has not been comprehensively explored.

Abstract

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Previous research has yielded inconsistent findings concerning the relationship between serum uric acid (UA) levels and sarcopenia. However, there is currently no research that comprehensively examines this relationship within the broader Chinese population. This study aims to explore the relationship between serum uric acid levels and sarcopenia in Chinese adults aged 45 and above, focusing specifically on age-related variations. The present study involved 10,938 participants of the 2015 China Health and Retirement Longitudinal Study (CHARLS). The associations between sarcopenia (including its components) and serum uric acid levels were evaluated using weighted logistic and weighted linear regression models. After categorizing participants by age groups, the subgroup analysis conducted allowed for a more detailed examination of age-related changes. Participants were stratified into quartiles based on their uric acid levels. Adjusted analyses revealed that a higher serum uric acid level was negatively associated with sarcopenia only in individuals aged 65 and older. Results from weighted linear regression analysis indicated a statistically significant positive correlation between serum uric acid levels and both handgrip strength (HGS) and skeletal muscle index (SMI). Moreover, the Q4 group (≥5.70 mg/dL) sustained this positive correlation across all ages. The results showed that higher UA levels were significantly associated with increased SMI and HGS in Chinese people aged 45 years and older. Elevated levels of blood uric acid may potentially exert a safeguarding influence against the onset of sarcopenia, particularly in individuals aged 65 years and above.

Introduction

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Sarcopenia is a degenerative condition that affects the skeletal muscles, leading to a gradual loss of muscle mass. It is linked with adverse consequences, including falls, functional deterioration, frailty, and mortality1,2,3, thereby emerging as a substantial global public health concern. In the past, sarcopenia was often regarded as an old-age disease, but recent studies have found that due to long-term bad living habits and aging, the muscle mass of some middle-aged people has decreased significantly, and the incidence of sarcopenia among them should not be underestimated4. Sarcopenia's global prevalence exhibits significant variation, spanning from 10% to 27%, contingent upon diagnostic criteria and target populations5. Prior research indicates a fluctuation in sarcopenia occurrence among elderly Asian individuals, ranging from 6.8% to 25.7%6,7,8,9. The overall prevalence of sarcopenia in China is approximately 16.4-18%, and the prevalence shows an upward trend with the increase of age10. The occurrence of sarcopenia not only impacts individuals and families but also exacerbates the burden on the social healthcare system. With the global population aging, the identification of modifiable risk factors for sarcopenia's development and progression is imperative in the endeavor to prevent or decelerate its advancement.

Sarcopenia, a complex illness, has been associated with multiple risk factors, such as decreased physical activity, reduced caloric intake, chronic inflammation, degradation of the neuromuscular junction, and oxidative stress11,12. As one of the important pathogenic factors of sarcopenia, reducing the damage caused by oxidative stress may be an effective way to prevent sarcopenia. Uric acid (UA), an essential endogenous antioxidant, removes reactive oxygen species (ROS), thereby mitigating the effects of oxidative stress. However, while UA exhibits significant antioxidant properties, it also shows paradoxical pro-oxidant activity13,14, thus the impact of UA on sarcopenia remains controversial. Existing studies suggest that uric acid (UA) may influence sarcopenia through the following mechanisms: On one hand, the antioxidant properties of UA can reduce reactive oxygen species (ROS)-induced damage to muscle cells, maintain the normal structure and function of muscle cells, and promote muscle protein synthesis, thereby exerting a positive effect on muscle mass and strength15. On the other hand, the pro-oxidant activity of UA may induce inflammatory responses, interfere with intracellular signaling pathways, and inhibit muscle protein synthesis, accelerating muscle protein degradation and leading to a reduction in muscle mass and strength16. Prior research suggests a positive correlation between UA levels and muscle mass in Chinese participants17, as well as muscle strength in Japanese and American participants18,19. Conversely, some studies indicate that elevated UA levels are linked to diminished muscle mass and decreased muscle strength20,21.

Existing studies on the association between serum uric acid and sarcopenia have several limitations, including small sample sizes, poor data quality, and a lack of precision in UA measurements. These issues make it difficult to draw robust conclusions regarding the relationship between uric acid levels and sarcopenia across different populations. Moreover, studies delving into the age-specific discrepancies between serum uric acid and sarcopenia are scarce. This study sought to perform a cross-sectional analysis utilizing nationally representative data from CHARLS to investigate the correlation between uric acid and sarcopenia among Chinese adults aged 45 years and older, concurrently exploring potential age-related disparities.

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Protocol

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The China Health and Retirement Longitudinal Study (CHARLS) was approved by the Institutional Review Board (IRB) of Peking University, with approval numbers IRB00001052-11014 and IRB00001052-11015. All participants provided informed consent before participating in the study, which was in line with ethical standards and the Declaration of Helsinki. This ensures that the data used from CHARLS complies with ethical research guidelines, including confidentiality and informed participation requirements.

Study population
The data for this study come from the CHARLS survey conducted by the National Development Research Institute of Peking University in 2015. The CHARLS was commenced in 2011 as a longitudinal investigation targeting adults aged 45 years and older in China. A thorough dataset is collected using structured interviews employing standardized questionnaires to investigate the socioeconomic factors and implications associated with aging. We used a multistage stratified probability proportional sampling approach to collect data from a sample of 17,708 participants. These participants resided in 10,257 households spanning 150 districts and 450 villages across 28 provinces in China22. The data included individual weighting variables to ensure that the survey sample was nationally representative. Other information about the CHARLS research design has been previously recorded6, and more content about the CHARLS study can be obtained from its official website (https://charls.pku.edu.cn/).

The inclusion criteria are as follows: (a) participants who were 45 years or older as of 2015, (b) participants who had available data regarding their sarcopenia status, and (c) participants who had undergone a UA blood test. Participants with kidney disease, tumors, and gout were excluded, considering the impact of these conditions on serum uric acid. As a result, the analysis comprised a total of 10,938 participants. Figure 1 depicts a detail of the exclusion process. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.

Assessment of sarcopenia status
This study utilized the diagnostic criteria established by the 2019 Asian Working Group for Sarcopenia (AWGS)23. Many previous studies have fully demonstrated the applicability and reliability of the AWGS diagnostic criteria in the Chinese middle-aged and elderly population24,25. Based on the 2019 AWGS, sarcopenia is characterized by diminished muscle mass in conjunction with reduced muscle strength or impaired physical performance.

Muscle strength
We assessed hand grip strength (HGS) on both hands using a handgrip dynamometer26. Each participant was tested in duplicate for both hands by holding the dynamometer at a right angle (90°). The mean maximum value from both hands, measured in kilograms (kg), was used for analysis. Insufficient HGS was considered less than 18 kg for women and less than 28 kg for men23.

Measurement of physical performance
In this test, the participant is asked to sit in a chair with their arms crossed over their chest. They then stand up and sit down five times consecutively as quickly as possible. The time taken to complete all five repetitions is recorded in seconds using a stopwatch. The chair should be placed against a stable surface, and participants should only use their legs to perform the task, without assistance from their arms27. People who cannot complete five chair stand tests within 12 s are considered to have decreased physical function23.

Skeletal muscle mass index (SMI)
In this study, appendicular skeletal mass (ASM) was calculated using the measurement formula recommended by the 2019 AWGS23. This formula presented in this study has been rigorously tested and demonstrated strong predictive accuracy in estimating ASM in a Chinese sample28,29. The formula is as follows:

ASM = 0.193 × body weight + 0.107 × height - 4.157 × sex - 0.037 × age - 2.631

Participants' height and weight were measured using a stadiometer and a digital floor scale, respectively, to the nearest 0.1 cm and 0.1 kg. The skeletal muscle mass index (SMI) was calculated by dividing ASM by the square of height (ASM/height²). Consequently, ASM/ height 2 values <5.4 kg/m2 in women and <7.0 kg/m2 in men indicated low muscle mass23.

Uric acid
Blood samples were collected from participants by medically trained staff from the Chinese Center for Disease Control and Prevention (Chinese CDC) following standard protocols. Blood samples were immediately stored at 4 °C and transported to local CDC laboratories or health centers for processing. The samples were then separated into plasma and buffy coat components, with plasma stored in 0.5 mL cryovials and frozen at -20 °C before being shipped to the China CDC in Beijing. Upon arrival, samples were stored at -80 °C until analysis at the Capital Medical University laboratory30. Uric acid (UA) levels were quantified using the UA Plus method, with the results expressed in milligrams per deciliter (mg/dL)22.

Covariates
The covariates comprised sociodemographic information and health-related characteristics31,32. The sociodemographic variables comprised age and gender, whereas the health-related covariates comprised body mass index (BMI), smoking and alcohol consumption history, chronic diseases, and blood test values. A questionnaire was used to collect data from the participants about their health conditions, which included things like hypertension, dyslipidemia, and diabetes. The blood test results encompassed various biomarkers, namely hemoglobin, creatinine, blood urea nitrogen (BUN), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), triglyceride (Tg), and C-reactive protein (CRP).

Statistical analysis
In view of the complex sampling design of CHARLS, all analyses were conducted using the R (version 4.2.2) software package and EmpowerStats 2.0. Participants were divided into quartile groups based on their serum uric acid concentration, with the lowest level representing the reference group (quartile group, Q1). Additionally, subgroup analysis was conducted based on age. Given the small number of individuals aged over 85, they are categorized into four age groups: <55, 55-64, 65-75, and ≥75. The missing values of covariates in this study were all less than 5%, and they were imputed using common imputation methods (median imputation or mean imputation). The analysis included measures such as the mean, median, standard deviation, range, and quartiles of continuous variables, as well as frequency tables of categorical variables. The median and interquartile range (IQR) were used to describe continuous variables with a non-normal distribution. Biomarker subsample weights, encompassing adjustments for household and individual responses, were employed in all analyses to generate estimations representative of the Chinese populace. The survey package in R was used for this purpose, utilizing functions such as svymean(), svyvar(), and svyquantile() to calculate means, standard deviations, medians, and quartiles. To examine differences in variable characteristics between groups, t-tests and survey Wilcoxon rank-sum tests were used for continuous variables, and Rao-Scott chi-square tests were used for weighted percentages of categorical variables, providing a comprehensive description of the entire population. A weighted logistic regression model was used to investigate the association between serum uric acid and sarcopenia. Weighted multivariable linear regression models were used to explore the associations between serum uric acid and HGS, FTSST, and SMI. The construction of the regression models was performed using the svyglm() function from the survey package. These models were adjusted for various covariates including age, sex, smoking history, drinking history, blood parameters (creatinine [Crea], blood urea nitrogen [BUN], high-density lipoprotein [HDL], low-density lipoprotein [LDL], total cholesterol, triglycerides, C-reactive protein [CRP]), and chronic diseases (hypertension, dyslipidemia, diabetes, or dysglycemia). A two-sided P < 0.05 was considered to indicate statistical significance.

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Results

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Characteristics of participants
This study included 10,938 Chinese participants aged 45-94 years, among whom the weighted prevalence of sarcopenia was 6.68%. The study cohort was stratified into four groups based on serum uric acid quartiles: Q1: ≤3.90 mg/dL, Q2: 4.00-4.70 mg/dL, Q3: 4.80-5.60 mg/dL, Q4: ≥5.70 mg/dL. Table 1 presents the weighted baseline characteristics across serum uric acid quartiles. The findings indicated a progressive increase in the weighted average age and BM...

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Discussion

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A cross-sectional study was conducted using nationally representative data to evaluate the association between UA and sarcopenia diagnosed using the AWGS 2019 algorithm among middle-aged and older Chinese adults. In this study, participants were Chinese adults aged 45-94 years, and their prevalence of sarcopenia was 6.68%. After adjusting for confounders, it was found that serum UA level was inversely associated with sarcopenia. There was a significant positive correlation between the quartile groups of serum UA levels a...

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Disclosures

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The authors declare no conflict of interest.

Acknowledgements

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This study is based on the baseline data of the China Health and Retirement Longitudinal Study (CHARLS). We extend our sincere gratitude to the dedicated CHARLS team for their contributions.

This study was supported by the China Postdoctoral Science Foundation (Grant No. 2022TQ0398), the First Affiliated Hospital of Chongqing Medical University Foundation (PYJJ2022-01), the Chongqing Key Discipline and Regional Key Medical Discipline Development Project (0201 [2023] 160 202412), National Natural Science Foundation of China (Grant Number: 82401836) and the Graduate Advisor Team Project of the First Affiliated Hospital of Chongqing Medical University (CYYY-DSTDXM-202407).

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
China Health and Retirement Longitudinal Study (CHARLS) Peking Universityhttps://charls.pku.edu.cn/.
EmpowerStats https://www.empowerstats.net/en/Version 2.0
Rhttps://www.r-project.org/Version 4.2.2 

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Serum Uric AcidSarcopenia AssociationChina Health StudyAge StratificationHandgrip StrengthSkeletal Muscle IndexWeighted Logistic RegressionWeighted Linear RegressionUric Acid QuartilesOlder Adults China

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