1. Urea kinetics were measured in six healthy men using prime/intermittent oral doses of [15N15N] urea, after five days consuming one of four diets which varied in their nitrogen content: a reference diet (REF, 70 g of protein and 11.2 g of N); a low-protein diet (LP, 30 g of protein and 4.8 g of N); a low-protein diet with 6.9 g of urea added (LP-U1, 30 g of protein and 8 g of N); a low-protein diet with 13.7 g of urea added (LP-U2, 30 g of protein and 11.2 g of N).
2. Apparent nitrogen balance on the REF diet was significantly better than on the LP or the LP-U1 diets. The addition of the higher level of urea in the LP-U2 diet enhanced apparent nitrogen balance compared with the LP or LP-U1 diets, and was not different to apparent nitrogen balance on the REF diet.
3. On the LP, LP-U1 and LP-U2 diets, the rate of endogenous urea production was not different, and was about 60% of that on the REF diet, a statistically significant difference. The addition of a dietary supplement of urea increased the rate of urea appearance in the urea pool in direct relation to the dose of urea taken. There was no difference in the rate of appearance between the REF and LP-U2 diets, for both of which the rate of appearance was significantly greater than on the LP diet.
4. The excretion of urea in urine on the LP diet was 62% of that on the REF diet, a significant difference. There was no significant difference in the rate of urea excretion between the REF, LP-U1 and LP-U2 diets.
5. The rate of urea hydrolysis by the colonic microflora on the REF diet was more than twice that on the LP or LP-U1 diets. Supplementation with urea at the higher level, LP-U2, significantly increased hydrolysis to the same level as on the REF diet. Most of the nitrogen derived from urea hydrolysis was retained in the metabolic pool (>80%), with no difference in the rate of retention between the REF and LP-U2 diets, both greater than the LP or LP-U1 diets.
6. The dietary supplements of urea increased the size of the body urea pool significantly. Renal clearance of urea was highest on the REF diet and decreased 13–29% on the low-protein diets. Bowel clearance was highest on the REF diet and decreased 46–55% on the low-protein diets. Neither urinary excretion of urea nor urea hydrolysis in the bowel were related simply to the concentration of urea in blood. Urea hydrolysis related most closely to the rate of appearance of urea in the urea pool.
7. The salvage of urea nitrogen was increased on the highest level of supplementation, but the overall sensitivity of the system was low, suggesting that other factors might be limiting for effective urea hydrolysis and the salvage of urea nitrogen.