Background/Purpose: The conventional low-purine dietary approach togout offers limited efﬁcacy, palatability, and sustainability, and promotesincreased consumption of reﬁned carbohydrates and saturated fat that canactually worsen gout’s cardiovascular (CV)-metabolic comorbidities. Incontrast, effective dietary approaches to reduce CV-metabolic conditions(including obesity) could also lower serum uric acid (SUA) levels bylowering adiposity and insulin resistance. Similarly, high-protein, low-carbohydrate diets such as the Atkins diet may lower SUA despite substantialpurine loading and ketogenesis. Indeed, a small study (n⫽13) that employeda high-protein diet with reduced calories found that mean SUA levelsdecreased from 9.6 to 7.9 mg/dL, with reduced gout attacks over 16 weeks(Ann Rheum Dis 2000). Additional beneﬁts included an improved lipidproﬁle. We investigated the SUA response to the Atkins diet amongoverweight or obese individuals over a 6 month period.Methods: Our study population was derived from the Dietary Interven-tion Randomized Controlled Trial (DIRECT) of overweight or obese partic-ipants (BMI ⱖ 27). The Atkins diet (i.e., high protein, low-carbohydrate, nocalorie restriction) was one of DIRECT’s intervention groups and was a focusof the current analysis. We used serum samples at -80°C to compare SUAlevels at baseline and 6 months among 74 participants with complete datasetsand analyzed the SUA level response as well as lipid proﬁle, weight change,fasting insulin levels, and glucose levels. Results: The mean age was 51 years and the mean BMI was 31. Mostparticipants (91%) were men. The overall rate of adherence to the diets inDIRECT was ⬎ 95% during our 6-month study period. Baseline SUA levelwas 6.0 mg/dL and the overall SUA change at 6 months was -0.8 mg/dL. Thischange varied substantially according to baseline characteristics (Table),particularly baseline SUA levels. Individuals (N⫽18) with SUA levels ⬎7mg/dL (above the saturation point) showed a decrease in mean SUA levelsfrom 7.9 to 5.5 mg/dL (p ⬍.0001). Of the 18, 11 (61%) reached SUA ⬍6mg/dL (the usual anti-gout SUA therapeutic target) and 6 (33%) reachedSUA level ⬍ 5mg/dL (the SUA therapeutic target for advanced gout)(Figure). Those with obesity and younger individuals (⬍50 years) tended tohave a larger SUA decline. Additional beneﬁts included signiﬁcant improve-ments in HDL-cholesterol, total cholesterol/HDL-C ratio, triglyceride levels,and fasting insulin levels (p ⬍.0001).Conclusion: Our ﬁndings suggest that the Atkins diet (i.e., a high proteindiet without calorie restriction) can reduce SUA levels despite substantialpurine loading. This effect may be more pronounced and clinically meaning-ful among those with hyperuricemia or obesity. Comparative effectivenessresearch with other proven CV-metabolic diets would help determine theoptimal dietary approach to lower SUA levels.