OBJECTIVE: To assess the effect of vitamin C supplementation on serum uric acid (SUA) by pooling the findings from published randomized controlled trials (RCTs). METHODS: A total of 2,082 publications identified through systematic search were subjected to the following inclusion criteria: 1) RCTs conducted on human subjects, 2) reported end-trial SUA means and variance, 3) study design with oral vitamin C supplementation and concurrent control groups, and 4) trial duration of at least 1 week. Trials that enrolled children or patients receiving dialysis were excluded. Two investigators independently abstracted trial and participant characteristics. SUA effects were pooled by random-effects models and weighted by inverse variance. RESULTS: Thirteen RCTs were identified in the Medline, EMBase, and Cochrane Central Register of Controlled Trials databases. The total number of participants was 556, the median dosage of vitamin C was 500 mg/day, trial size ranged from 8-184 participants, and the median study duration was 30 days. Pretreatment SUA values ranged from 2.9-7.0 mg/dl (Système International d'Unités [SI units]: 172.5-416.4 μmoles/liter). The combined effect of these trials was a significant reduction in SUA of -0.35 mg/dl (95% confidence interval -0.66, -0.03 [P = 0.032]; SI units: -20.8 μmoles/liter). Trial heterogeneity was significant (I(2) = 77%, P < 0.01). Subgroup analyses based on trial characteristics indicated larger reductions in uric acid in trials that were placebo controlled. CONCLUSIONS: In aggregate, vitamin C supplementation significantly lowered SUA. Future trials are needed to determine whether vitamin C supplementation can reduce hyperuricemia or prevent incident and recurrent gout.