Effect of excess xylitol on nitrogen and glucose metabolism in parenterally fed rats

The objectives of this study were to investigate the effects of an excess of xylitol on nitrogen balance and glucose metabolism in parenterally fed rats. Female Sprague-Dawley rats (200-250 g, n = 17) were catheterized for total parenteral nutrition and then randomized into two groups based on subsequent diet. The two diets used were isonitrogenous (1.5 g of nitrogen per kilogram per day) and isocaloric, with half the calories (125 kcal/kg per day) being derived from lipid (125 kcal/kg per day) and the other half from either glucose or xylitol (125 kcal/kg per day). The rats were fed a half-strength total parenteral nutrition diet for the day after surgery and a full-strength total parenteral nutrition diet for the following 4 days. Urines were collected daily for the determination of nitrogen balance. On day 5, the rats were given a 7- to 8-hour infusion of 6,6-d₂ glucose (6 mg/h and 2-d₁ glucose (12 mg/h). At the conclusion of the isotope infusion period, the rats were killed and blood was collected. Urine output was increased by 22% per day in the xylitol-treated rats, and they excreted 46.5 mmol of xylitol per liter per kilogram per day (7.1 g/kg per day, ~22.7% of dose). The xylitol group lost weight, had poorer nitrogen balance (341 ± 31 vs 83 ± 29 mg/kg per day [mean ± standard error of the mean], p < .05), and developed fatty livers. Analysis of the liver fat distribution pattern indicated that the source of the excess hepatic lipid was dietary fat. Substitution of xylitol for glucose had no effect on total glucose appearance as measured with 6,6-d₂ glucose (1238 ± 76 vs 1294 ± 113 mg/kg per day), but the rate of glucose cycling was markedly reduced (1518 ± 101 vs 764 ± 63 mg/kg per day, p < .05). The adverse effects of xylitol in this study were due to a caloric deficit secondary to a combination of (1) exceeding the renal threshold for xylitol and (2) hepatic steatosis.