Diet Interventions, by Race, Evaluated as Complementary Treatments for Pain (DIRECTPain) Project Summary Knee osteoarthritis (OA) is the most prevalent form of arthritis and a significant cause of disability in the U.S. and race is a risk factor for poor outcomes. Non-Hispanic Black individuals (NHB) report greater OA-related disability and pain severity compared to their Non-Hispanic White (NHW) counterparts. These disparities are reinforced through social and biological mechanisms, ultimately resulting in dramatic racial disparities in pain experience and associated quality of life. Current national efforts to reduce analgesic utilization highlight the critical need for safe and effective alternatives for pain relief for underserved/at-risk populations. Low-carbohydrate diets (LCDs) reduce inflammation and pain independent of weight loss, indicating that diet interventions offer a non- pharmacological complementary treatment. However, racial differences exist in metabolism that are rarely addressed in diet interventions. NHBs tend to have low insulin sensitivity and are at greater risk for developing metabolic disorders, suggesting altered carbohydrate responses. Therefore, a LCD may have greater pain- reducing effects in NHBs and provide a complementary (or alternative) treatment for pain. Here, we will recruit male and female NHB (n=100) and NHW (n=100) adults with knee OA to complete our two-phase protocol. Phase 1 will involve a 3-week diet run-up that will allow for quantification of pain measures, psychosocial variables (socioeconomic status, nutritional knowledge, proximity to grocery stores, food insecurity), and diet quality to provide a baseline for comparison. Phase 2 will be a 6-week diet intervention (LCD or USDA diet) in which both groups will be provided with all meals at the direction of study personnel and input from participants. Evoked pain, measures of pain disability, severity, catastrophizing, and interference will be assessed every 3 weeks in addition to QOL measures, mood, and depression. Physiological variables will be assessed through blood draws (inflammatory profile) and dual-energy X-ray absorptiometry scans (DXA; body composition, visceral fat) at the end of Phases 1 and 2. This will be the first study to examine the efficacy of these diets to reduce knee OA pain with an emphasis on race and interactions with biopsychosocial variables. Changes in all pain measures following Phase 2 will be assessed with respect to published measures of clinically-meaningful differences in pain and disability, as well as for statistical significance. The central hypothesis is that the LCD will improve pain and QOL in participants with knee OA with a greater effect in NHBs than NHWs.