ABSTRACT: Background:Gout is a frequently occurring, complex rheumatologic form of inflammatory arthritis caused by the accumulation of serum uric acid (sUA) and deposition of uric acid crystals in the joints and tissues of the body. Hyperuricemia is also a significant independent risk factor for all-cause and cardiovascular morbidity and mortality and is associated with hypertension, diabetes, obesity, and osteoarthritis. However, patient adherence to prescribed urate-lowering therapies ranges from 20% to 70%, suggesting that other additional strategies, such as dietary intervention with specific, efficacious foods or beverages, may be necessary to mitigate the risk of arthritis, as well as other comorbidities. Tart cherry juice (TCJ) has been used for decades by some for gout based largely on anecdotal evidence of its efficacy and its antioxidant and anti-inflammatory properties. Objectives:We designed this study to test the effect of TCJ on uricemia, lipidemia, glycemia, and inflammation in at-risk overweight and obese humans with a specific hypothesis that TCJ consumption would reduce sUA concentrations. Methods:In this randomized, placebo-controlled crossover study, we recruited overweight and obese participants with body mass index (BMI) >25.0 kg/m2 (n = 26, 18 women/8 men, 41 ±11 y; BMI 31.3 ± 6.0; 12 obese, 14 overweight) to consume 240 mL/d (8 oz/d) of either TCJ or placebo beverage, for 4 wk each with a 4-wk intervening washout period followed by 4 wk of the alternate beverage. Results:TCJ significantly reduced sUA concentration by 19.2% (P < 0.05) and reduced by 19.4% (P = 0.09) and 6.3% (P = 0.08) proinflammatory high-sensitivity C-reactive protein and monocyte chemoattractant protein-1, respectively. The participants in this study displayed risk ratios indicating increased cardiovascular disease risk and insulin resistance but no differences in the pre- and postintervention groups of either placebo or TCJ groups. Conclusion:Collectively, the data suggest that 100% TCJ reduces sUA concentrations, mitigating hyperuricemia associated with gouty arthritis. This trial was registered at clinicaltrials.gov as NCT03636529.