Hydrolyzed casein and whey protein meals comparably stimulate net whole-body protein synthesis in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion

Abstract

Background & aims: Muscle wasting commonly occurs in COPD, negatively affecting outcome. The aim was to examine the net whole-body protein synthesis response to two milk protein meals with comparable absorption rates (hydrolyzed casein (hCAS) vs. hydrolyzed whey (hWHEY)) and the effects of co-ingesting leucine.

Methods: Twelve COPD patients (GOLD stage II-IV) with nutritional depletion, were studied following intake of a 15 g hCAS or hWHEY protein meal with or without leucine-co-ingestion, according to a double-blind randomized cross-over design. The isotopic tracers L-[ring-(2)H5]-Phenylalanine, L-[ring-(2)H2]-Tyrosine, L-[(2)H3]-3-Methylhistidine (given via continuous intravenous infusion), and L-[(15)N]-Phenylalanine (added to the protein meals) were used to measure endogenous whole-body protein breakdown (WbPB), whole-body protein synthesis (WbPS), net protein synthesis (NetPS), splanchnic extraction and myofibrillar protein breakdown (MPB). Analyses were done in arterialized-venous plasma by LC/MS/MS.

Results: WbPS was greater after intake of the hCAS protein meal (P < 0.05) whereas the hWHEY protein meal reduced WbPB more (P < 0.01). NetPS was stimulated comparably, with a protein conversion rate greater than 70%. Addition of leucine did not modify the insulin, WbPB, WbPS or MPB response.

Conclusions: Hydrolyzed casein and whey protein meals comparably and efficiently stimulate whole-body protein anabolism in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion. This trial was registered at clinicaltrials.gov as NCT01154400.

Keywords: Chronic obstructive pulmonary disease; Hydrolyzed casein protein; Hydrolyzed whey protein; Leucine; Nutritionally depleted; Whole-body protein kinetics.

Figure 1

Overview of study design. Patients received four different protein meals (hydrolyzed casein versus hydrolyzed whey protein meal with or without added leucine), one on each experimental test day, according to a double-blind randomized cross-over design.

Figure 2

Mean (±SEM) plasma L-[ring-²H₅]-Phenylalanine (L-[ring-²H₅]-PHE, panel a), L-[ring-²H₂]-Tyrosine (L-[ring-²H₂]-TYR, panel b), L-[ring-²H₄]-Tyrosine (L-[ring-²H₄]-TYR, panel c), and L-[¹⁵N]-Phenylalanine (L-[¹⁵N]-PHE (panel c) enrichments expressed as tracer-tracee ratio corrected for background enrichment (cTTR) before and after intake of a hydrolyzed casein (hCAS) and hydrolyzed whey (hWHEY) protein meal (t=90 min). Plasma L-[ring-²H₅]-PHE enrichment: time effect, P<0.0001; time × protein meal interaction, P<0.0001. Plasma L-[ring-²H₂]-TYR: time effect, P<0.0001; time × protein meal interaction, P<0.0001. Plasma L-[ring-²H₄]-TYR: time effect, P<0.0001; time × protein meal interaction, P<0.0001. Plasma L-[¹⁵N]-PHE enrichment: time effect, P<0.0001; protein meal effect, P=0.0003; time × protein meal interaction, P<0.0001. Significance of difference between hCAS and hWHEY: *: P<0.05; **: P<0.01; ***: P<0.001.

Figure 3

Mean (±SEM) plasma phenylalanine (pPHE, panel a), leucine (pLEU, panel b) and essential amino acid (pEAA, panel c) concentrations before and after intake of a hydrolyzed casein (hCAS), hydrolyzed casein with leucine addition (hCAS+LEU), hydrolyzed whey (hWHEY), and hydrolyzed whey with leucine addition (hWHEY+LEU) protein meal. pPHE concentration: time effect, P<0.0001; protein meal effect, P<0.0001; time × protein meal interaction, P=0.0216. pLEU concentration: time effect, P<0.0001; protein meal effect, P<0.0001; time × protein meal interaction, P<0.0001. pEAA concentration: time effect, P<0.0001; protein meal effect, P<0.0001; time × protein meal interaction, P<0.0001.*hCAS significantly different from hWHEY, P<0.05. **hCAS+LEU significantly different from hWHEY+LEU, P<0.05. ^#hCAS significantly different from hCAS+LEU, P<0.05. ^$hWHEY significantly different from hWHEY+LEU, P<0.05.

Figure 4

Mean (±SEM) plasma L-[¹⁵N]-Phenylalanine concentration (pL-[¹⁵N]-PHE) and phenylalanine concentration (pPHE) after intake of a hydrolyzed casein (hCAS) (panel a) and hydrolyzed whey (hWHEY) (panel b) protein meal.

Figure 5

Plasma insulin concentration after intake of a hydrolyzed casein protein (hCAS), hydrolyzed casein with leucine addition (hCAS+LEU), hydrolyzed whey (hWHEY), and hydrolyzed whey with leucine addition (hWHEY+LEU) protein meal. Data are also expressed as the 4h postprandial peak area under the curve (AUC). AUC insulin: protein meal effect, P=0.0038.

Figure 6

Mean (±SEM) endogenous (endo) (panel a) and exogenous (exo) (panel b) whole-body rate of appearance of phenylalanine (WbRa PHE) after intake of a hydrolyzed casein protein (hCAS), hydrolyzed casein with leucine addition (hCAS+LEU), hydrolyzed whey (hWHEY), and hydrolyzed whey with leucine addition (hWHEY+LEU) protein meal. Endo WbRa: time effect, P=0.0013; protein meal effect, P<0.0001; time × protein meal interaction, P<0.0001. Exo WbRa: time effect, P<0.0001. *hCAS significantly different from hWHEY, P<0.01. **hCAS+LEU significantly different from hWHEY+LEU, P<0.05.

Figure 7

Correlation between net protein synthesis (NetPS) expressed as the total amount over four hours and phenylalanine intake (PHE intake) of a hydrolyzed casein (hCAS) (r = 0.88; NetPS = 0.93 · PHE intake − 18.3), hydrolyzed casein with leucine addition (hCAS+LEU) (r=0.83; net NetPS = 0.88 · PHE intake − 15.1), hydrolyzed whey (hWHEY) (r=0.92; NetPS = 0.84 · PHE intake − 16.4), and hydrolyzed whey with leucine addition (hWHEY+LEU) (r=0.94; NetPS = 1.02 · PHE intake − 24.0) protein meal. All correlations were statistically significant (P<0.01) and linear regression showed no significant difference between the slopes (P=0.9374).