Adaptive responses to very low protein diets: the first comparison of ketoacids to essential amino acids

Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days before hospital admission and following a four-day equilibration, a five-day nitrogen balance (BN) was performed. Whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Even though the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Nitrogen conservation with KA was due to a reduction in urea nitrogen appearance. Rates of WBPT measured during fasting and feeding did not differ between the KA or EAA regimens. During both regimens, feeding decreased protein degradation, whereas protein synthesis was unchanged. Although feeding stimulated leucine oxidation, rates were 50 to 100% lower than reported in CRF patients consuming 0.6 or 1.0 g protein/kg/day. Thus, neutral Bn with the VLPD regimen is achieved by a marked reduction in amino acid oxidation and a postprandial inhibition of protein degradation.