BACKGROUND: The metabolic effects of diets high in vegetable protein have not been assessed despite much recent interest in the effect of soy proteins in reducing serum cholesterol. OBJECTIVE: We assessed the metabolic effects of diets high in vegetable protein (specifically, wheat gluten) on serum lipids, uric acid concentrations, and renal function. DESIGN: Twenty hyperlipidemic men and women consumed isoenergetic test (high-protein) and control metabolic diets for 1 mo in a randomized crossover design. In the high-protein diet, 11 f the total dietary energy from starch in the control bread was replaced by vegetable protein (wheat gluten), resulting in 27 f total energy from protein compared with 16 n the control diet. In other respects, the 2 diets were identical. RESULTS: Compared with the control, the high-protein diet resulted in lower serum concentrations of triacylglycerol (by 19.2 /- 5.6 P = 0.003), uric acid (by 12.7 /- 2.0 P < 0.001), and creatinine (by 2.5 /- 1.1 P = 0.035) and higher serum concentrations of urea (by 42.2 /- 5.8 P < 0.001) and a higher 24-h urinary urea output (by 99.2 /- 17.2 P < 0.001). No significant differences were detected in total or HDL cholesterol or in the renal clearance of creatinine. LDL oxidation, assessed as the ratio of conjugated dienes to LDL cholesterol in the LDL fraction, was lower with the high-protein diet (by 10.6 /- 3.6 P = 0.009). CONCLUSIONS: High intakes of vegetable protein from gluten may have beneficial effects on cardiovascular disease risk by reducing oxidized LDL, serum triacylglycerol, and uric acid. Further studies are required to assess the longer-term effects on renal function.