Preserved anabolic threshold and capacity as estimated by a novel stable tracer approach suggests no anabolic resistance or increased requirements in weight stable COPD patients

Abstract

Assessing the ability to respond anabolic to dietary protein intake during illness provides important insight in the capacity of lean body mass maintenance. We applied a newly developed stable tracer approach to assess in one session in patients with chronic obstructive pulmonary disease (COPD) and healthy older adults both the minimal amount of protein intake to obtain protein anabolism (anabolic threshold) and the efficiency of dietary protein to promote protein anabolism (anabolic capacity). We studied 12 clinically and weight stable patients with moderate to very severe COPD (mean±SE forced expiratory volume in 1s: 36±3% of predicted) and 10 healthy age-matched older adults. At 2-h intervals and in consecutive order, all participants consumed a mixture of 0.0, 0.04, 0.10 and 0.30g hydrolyzed casein protein×kg ffm-1×2h-1 and carbohydrates (2:1). We assessed whole body protein synthesis (PS), breakdown (PB), net PS (PS-PB) and net protein balance (phenylalanine (PHE) intake - PHE to tyrosine (TYR) hydroxylation) by IV primed and continuous infusion of L-[ring-2H5]PHE and L-[13C9,15N]-TYR. Anabolic threshold (net protein balance=0) and capacity (slope) were determined on an individual basis from the assumed linear relationship between protein intake and net protein balance. We confirmed a linear relationship between protein intake and net protein balance for all participants (R2 range: 0.9988-1.0, p≤0.0006). On average, the anabolic threshold and anabolic capacity were comparable between the groups (anabolic threshold COPD vs. healthy: 3.82±0.31 vs. 4.20±0.36μmol PHE×kg ffm-1×hr-1; anabolic capacity COPD vs. healthy: 0.952±0.007 and 0.954±0.004). At protein intake around the anabolic threshold (0.04 and 0.10g protein×kg ffm-1×2h-1), the increase in net PS resulted mainly from PB reduction (p<0.0001) whereas at a higher protein intake (0.30g protein×kg ffm-1×2h-1) PS was also stimulated (p<0.0001). The preserved anabolic threshold and capacity in clinically and weight stable COPD patients suggests no disease related anabolic resistance and/or increased protein requirements. ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.