A critical evaluation of the anabolic response after bolus or continuous feeding in COPD and healthy older adults.

After bolus and continuous enteral feeding of the same protein, different digestion and absorption kinetics and anabolic responses are observed. Establishing which mode of feeding has the highest anabolic potential in patients with chronic obstructive pulmonary disease (COPD) may aid in the prevention of muscle wasting, but an important confounding factor is the duration of assessments after bolus feeding. We hypothesized that the anabolic response to bolus and continuous feeding in COPD patients is comparable when methodological issues are addressed. Twenty-one older adults (12 patients with stage II-IV COPD and 9 healthy controls) were studied after intake of a fast-absorbing hydrolyzed casein protein-carbohydrate mixture either as a single bolus or as small sips (crossover design). Whole body protein synthesis (PS), breakdown (PB), net PS (PS - PB) protein efficiency (netPSPE), net protein balance (phenylalanine (PHE) intake - PHE hydroxylation) protein efficiency (netBalPE), and splanchnic PHE extraction (SPEPHE) were assessed using stable isotope tracer methodology. Bolus feeding assessments were done at 90, 95, and 99% of the calculated duration of the anabolic response. At 99%, netBalPE was higher for sip feeding than bolus feeding in both groups (P<0.0001). Nevertheless, bolus feeding was associated with a lower SPEPHE (P<0.0001) and higher netPSPE (P<0.0001). At 90% compared with 99%, PS and netBalPE after bolus feeding was significantly overestimated. In conclusion, several factors complicate a comparison of the anabolic capacity of bolus and continuous feeding in acute studies, including the critical role of SPE calculation and assumptions, and the duration of postprandial assessments after bolus feeding.

Whole body protein anabolism in COPD patients and healthy older adults is not enhanced by adding either carbohydrates or leucine to a serving of protein.

BACKGROUND & AIMS: Carbohydrates (CHO) and leucine (LEU) both have insulinotropic properties, and could therefore enhance the protein anabolic capacity of dietary proteins, which are important nutrients in preventing muscle loss in patients with Chronic Obstructive Pulmonary Disease (COPD). LEU is also known to activate protein anabolic signaling pathways independent of insulin. Based on our previous findings in COPD, we hypothesized that whole body protein anabolism is enhanced to a comparable extent by the separate and combined co-ingestion of CHO and LEU with protein. METHODS: To disentangle the protein anabolic effects of CHO and/or free LEU when co-ingested with a high-quality protein, we studied 10 patients with moderate to very severe COPD and dyspnea (GOLD: II-IV, mMRC dyspnea scale ≥ 2), at risk for muscle loss, and 10 healthy age- and gender-matched controls. On four occasions, in a single-blind randomized crossover design, each subject ingested a drink containing 0.6 g/kg fat-free mass (ffm) hydrolyzed casein protein with, a) no add-ons (protein), b) 0.3 g/kg ffm CHO (protein + CHO), c) 0.095 g/kg ffm leucine (protein + LEU), d) both add-ons (protein + CHO + LEU). Whole body protein breakdown (PB), protein synthesis (PS), and net protein balance (= PS - PB) were measured by IV primed and continuous infusion of L-[ring-2H5]-phenylalanine and L-[13C9,15N]-tyrosine. L-[15N]-phenylalanine was added to the protein drinks to measure splanchnic extraction. RESULTS: In both groups, whole body PS, PB and net protein balance responses were comparable between the four protein drinks, despite higher postprandial plasma LEU concentrations for the LEU supplemented drinks (P < 0.05), and higher insulin concentrations for the CHO supplemented drinks as compared to the protein only drink (P < 0.05). CONCLUSIONS: Adding CHO and/or LEU to a serving of high-quality protein does not further augment whole body protein anabolism in dyspneic COPD patients at risk for muscle loss or healthy older adults. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.

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.

BACKGROUND & AIMS: 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). METHODS: We studied 12 clinically and weight stable patients with moderate to very severe COPD (mean ± SE forced expiratory volume in 1 s: 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 0.30 g hydrolyzed casein protein×kg ffm-1×2 h-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. RESULTS: 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 ± 0.36 µmol 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 0.10 g protein×kg ffm-1×2 h-1), the increase in net PS resulted mainly from PB reduction (p < 0.0001) whereas at a higher protein intake (0.30 g protein×kg ffm-1×2 h-1) PS was also stimulated (p < 0.0001). CONCLUSIONS: The preserved anabolic threshold and capacity in clinically and weight stable COPD patients suggests no disease related anabolic resistance and/or increased protein requirements. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.