Efficacy of Theobromine and Its Metabolites in Reducing the Risk of Uric Acid Lithiasis

Abstract

Uric acid lithiasis accounts for about 10% of all types of renal lithiasis. The most common causes of uric acid lithiasis are low urinary pH, followed by high concentration of urinary uric acid, and low diuresis. Treatment of patients consists of alkalinization of urine, reducing the consumption of purine-rich foods, and administration of xanthine oxidase inhibitors, because there are no established therapeutic inhibitors of uric acid crystallization. We recently found that theobromine inhibited uric acid crystallization in vitro, and that the increased urinary level of theobromine following its oral consumption was associated with the prevention of uric acid crystallization. In this study, we evaluated the inhibitory effects of theobromine metabolites and other methylxanthine-related compounds on uric acid crystallization. We also measured the urinary concentrations of theobromine and its metabolites in samples from healthy individuals and patients with uric acid stones and compared the extent of uric acid supersaturation and uric acid crystal formation in these different samples. Theobromine and other methylxanthines that lacked a substituent at position 1 inhibited uric acid crystallization, but other methylxanthines did not have this effect. Individuals with clinical parameters that favored uric acid crystallization did not develop uric acid crystals when theobromine and its metabolites were in the urine at high levels. Thus, theobromine and its metabolites reduced the risk of uric acid lithiasis.