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.
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