Serum uric acid, sarcopenia, and muscle strength: A systematic review of dose-response evidence with exploratory...

Serum uric acid (SUA) has antioxidant activity but is also linked to metabolic, renal, and inflammatory pathways that may impair skeletal muscle. We assessed whether outcome-specific dose-response evidence identifies a reproducible SUA range associated with better muscle health.

We reviewed studies reporting three or more SUA categories, category-specific outcomes, or nonlinear models or thresholds. Muscle outcomes were analysed separately by construct and sex. Restricted cubic spline synthesis required at least five independent compatible clusters; small-sample inference used clustered CR2 robust variance.

Nineteen reports were retained. Only sex-specific cross-sectional handgrip strength (HGS) supported exploratory nonlinear pooling. Male and female models each comprised five independent clusters, with 13 and 14 non-reference contrasts. Point maxima were 5.92 mg/dL in men (+0.31 kg versus 5.0 mg/dL; 95% CI -2.95 to 3.57; P for nonlinearity = 0.466) and 5.60 mg/dL in women (+0.05 kg; 95% CI -0.78 to 0.87; P for nonlinearity = 0.597). HTZ tests were unreliable (denominator degrees of freedom <0.6), and leave-one-study-out models contained only four clusters. One repeated-measures study reported a 6.79-mg/dL threshold without uncertainty or replicable coefficients. Other outcomes could not be pooled because of sparse, heterogeneous, overlapping, or incomplete data. Certainty was very low for all nine outcome bodies.

Observational evidence does not identify a clinically defensible SUA range that optimizes muscle health. The sex-specific HGS maxima and 6.79-mg/dL threshold are hypothesis-generating, not treatment targets. Prospective sex-specific studies with harmonized outcomes, complete category covariance, and externally validated nonlinear models are needed.