High Uric Acid Linked to 78% Greater Risk of Muscle Loss in US Adults

Sarcopenia — the progressive loss of skeletal muscle mass, strength, and function — affects 7–12% of adults globally and is rising alongside population aging. Identifying modifiable or measurable risk factors is critical for early intervention. Serum uric acid (SUA), the end product of purine metabolism, has been linked to inflammation, oxidative stress, and metabolic disease, but its relationship with muscle loss has remained contradictory across prior studies, with some suggesting harm and others pointing to antioxidant benefits.

This cross-sectional study used four cycles of NHANES data (2011–2018) to examine the association between SUA levels and relative muscle loss in 8,967 non-pregnant US adults aged ≥18 years. Muscle mass was measured by DXA, and relative muscle loss was defined by the FNIH consensus as appendicular lean mass (ALM) divided by BMI falling below 0.789 in men and 0.512 in women — thresholds validated in prior NHANES research. SUA was measured via standardized laboratory methods, and participants were divided into quintiles. Multivariate logistic regression was applied with three progressively adjusted models, and restricted cubic spline (RCS) regression was used to visualize dose-response relationships.

The study population had a mean age of 39.4 years and mean SUA of 5.3 mg/dL. Among the 762 individuals identified with relative muscle loss (weighted prevalence 7.1%), prevalence ranged from 5.3% in the lowest SUA quintile to 10.5% in the highest. In the fully adjusted model, participants in the highest SUA quintile had an OR of 1.78 (95% CI: 1.24–2.56) compared to the lowest quintile. Two alternative sarcopenia definitions (EWGSOP height-adjusted and FNIH absolute ALM criteria) showed consistent directional associations, supporting the robustness of findings.

RCS modeling revealed a nonlinear dose-response in the overall population but linear relationships in men, individuals with BMI <25 kg/m², and those exceeding recommended physical activity levels — subgroups where stronger associations and interaction effects (p<0.05) were also identified. These subgroup patterns suggest that lean and highly active individuals may be particularly vulnerable to SUA-driven muscle catabolism, possibly because oxidative stress mechanisms dominate when protective metabolic buffering is lower.

The authors propose several biological mechanisms: elevated SUA may promote reactive oxygen species (ROS) accumulation, impairing mitochondrial function and accelerating muscle protein degradation. SUA can also trigger NLRP3 inflammasome activation, elevating IL-1β and IL-6, which suppress muscle protein synthesis. Additionally, hyperuricemia is linked to insulin resistance, which further blunts anabolic signaling in skeletal muscle. While SUA has antioxidant properties at physiological concentrations, chronically elevated levels appear to shift the balance toward pro-oxidant and pro-inflammatory states that are detrimental to muscle maintenance.