Elsevier

Clinical Nutrition

Volume 33, Issue 2, April 2014, Pages 211-220
Clinical Nutrition

Randomized control trials
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

https://doi.org/10.1016/j.clnu.2013.06.014Get rights and content

Summary

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-2H5]-Phenylalanine, L-[ring-2H2]-Tyrosine, L-[2H3]-3-Methylhistidine (given via continuous intravenous infusion), and L-[15N]-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.

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is considered a systemic disease in which muscle wasting, as independent co-morbidity, negatively affects mortality.1 The exact mechanisms underlying muscle wasting in COPD are complex and multifactorial. We have observed disturbances in protein turnover and intermediary amino acid metabolism on whole-body and skeletal muscle level.2, 3, 4, 5 This suggests that dietary proteins, through enhancing protein anabolism, could help preserve and increase muscle mass in COPD patients. In particular the milk proteins casein and whey are of interest as both are high-quality proteins6 because of their high essential amino acid (EAA) content. Previous studies indicate that primarily the EAA stimulate muscle protein synthesis and improve anabolism in healthy older adults,7, 8 with a specific role for the amino acid leucine.9

Although casein and whey are both high-quality proteins, studies comparing their anabolic capacity in healthy individuals show variable results. In young men, several studies report a better whole-body leucine balance after casein protein intake, despite the higher leucine content of whey protein.10, 11 In elderly, researchers find a greater stimulation of protein anabolism in response to whey protein intake.12, 13 A complicating factor in several recent studies that examine the muscle anabolic response to milk proteins is the lack of information on muscle protein breakdown. With only information on muscle protein synthesis, the calculation of net muscle protein gain is not possible.14 In the present study we chose a protocol that is able to measure net whole-body protein synthesis, can delineate the underlying mechanisms (i.e. synthesis increase or breakdown decrease) and allowed us to have the same patient come back four times.

Several factors can influence the anabolic capacity of a protein meal besides the EAA or leucine content, including the relative proportion of the individual branched-chain amino acids (BCAA), the mode of administration (sip versus bolus meal),10 and the presence of carbohydrates15 that affects insulin kinetics.16 To exclusively compare protein meals for differences in amino acid profile, it is of key importance to use comparable amounts of protein and carbohydrates and to correct for differences in digestion and absorption pattern.

The purpose of the present study was to compare the anabolic properties of a hydrolyzed casein and whey protein bolus meal with and without co-ingestion of leucine in COPD patients characterized by nutritional depletion. A bolus meal was chosen as it is a more physiological approach compared to continuous feeding and thereby the preferred therapeutic modality to provide supplemental proteins in COPD. All meals contained a similar amount of proteins and carbohydrates. Hydrolyzed proteins were used to eliminate possible differences in digestion and absorption rates. Furthermore, we added leucine to the protein meals to 40% of its EAA content to examine whether leucine addition would further enhance the anabolic capacity of the meals.

Section snippets

Subjects

The study population consisted of 12 patients (7 male, 5 female) ranging from 43 to 77 yrs, with moderate to severe airflow obstruction. Eligible patients were recruited from March 2010 to June 2011 from Little Rock, AR and surrounding areas and had COPD stage II–IV according to the established Gold Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.17 All patients were in clinically stable condition and not suffering from a respiratory tract infection or exacerbation of their

Results

Twelve COPD patients whom were nutritionally depleted participated in the study and were analyzed for the primary outcome. Two out of 12 patients dropped out early (after one and two study days respectively). Patients (Table 2) had moderate to severe airflow obstruction (FEV1 predicted: 45 ± 4%). Six patients had one or more exacerbations of their disease in the past year of which four required hospitalization.

Discussion

In the present study, we found that a bolus meal of casein vs. whey protein, containing a similar amount of carbohydrates and with comparable absorption characteristics, stimulated net whole-body protein synthesis comparably and efficiently in COPD patients characterized by nutritional depletion. Co-ingestion of leucine did not stimulate the net whole-body protein synthesis response further.

Conflict of interest

None.

Acknowledgments

RJ was involved in the conduct of the research, data analysis and writing of the manuscript. NEPD and MPKJE designed the research and were involved in the conduct of the research, data analysis and writing of the manuscript. MLE and PJA were involved in the recruitment of study participants. None of the authors had any financial or personal interest in any company or organization sponsoring the research, including advisory board affiliations.

The project described was sponsored by award number

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