Renate Jonker1, Nicolaas E P Deutz1, Annemie M W J Schols2, Eugene A Veley3, Rajesh Harrykissoon4, Anthony J Zachria4, Mariëlle P K J Engelen5. 1. Center for Translational Research in Aging & Longevity, Dept. of Health and Kinesiology, Texas A&M University, College Station, TX, USA. 2. NUTRIM School for Nutrition, Toxicology and Metabolism, Dept. of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands. 3. Dept. of Medicine, Div. of Pulmonary & Critical Care Medicine, Baylor Scott & White Medical Center, College Station, TX, USA. 4. Center for Pulmonary and Sleep Disorders, College Station Medical Center, College Station, TX, USA. 5. Center for Translational Research in Aging & Longevity, Dept. of Health and Kinesiology, Texas A&M University, College Station, TX, USA. Electronic address: mpkj.engelen@ctral.org.
Abstract
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, mMRCdyspnea 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.
RCT Entities:
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 COPDpatients at risk for muscle loss or healthy older adults. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.
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