ABSTRACT: OBJECTIVES:To examine the effects of high-fiber, isocaloric, macronutrient substitutions on bloating. METHODS:The OmniHeart study is a randomized 3-period crossover feeding trial conducted from April 2003 to June 2005. Participants were provided 3 isocaloric versions of high-fiber (?30 g per 2,100 kcal) diet, each different in carbohydrate, protein, and unsaturated fat composition. Each feeding period lasted for 6 weeks with a 2- to 4-week washout period between diets. Participants reported the presence and severity of bloating at baseline (participants were eating their own diet) and at the end of each feeding period. RESULTS:One hundred sixty-four participants were included in the analysis (mean age: 53.1 years; 45% women; 55% black). The prevalence of bloating at baseline and at the end of the carbohydrate-rich, protein-rich, and unsaturated fat-rich diet period was 18%, 24%, 33%, and 30%, respectively. Compared with baseline, the relative risk of bloating for the carbohydrate-rich, protein-rich, and unsaturated fat-rich high-fiber diet was 1.34 (95% confidence interval [CI]: 0.93, 1.92), 1.78 (95% CI: 1.32, 2.40), and 1.63 (95% CI: 1.17, 2.26), respectively. The protein-rich diet increased the risk of bloating more than the carbohydrate-rich diet (relative risk = 1.40; 95% CI: 1.03, 1.88). Bloating did not significantly vary between protein-rich vs unsaturated fat-rich or unsaturated fat-rich vs carbohydrate-rich diets. Black participants compared with non-black participants had a higher risk of bloating after all 3 versions of the high-fiber OmniHeart diet (P-value for interaction = 0.012). DISCUSSION:Substitution of protein with carbohydrate may be an effective strategy to decrease bloating among individuals experiencing gastrointestinal bloating from a high-fiber diet.