Supplementation of a Leucine-Enriched Dairy Protein Blend

Healthy Clinical Trial

Official title:

Supplementation of a Leucine-Enriched Dairy Protein Blend: Effects on Plasma Amino Acids in Older Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03712761
• Other study ID #: 2502
• Status: Active, not recruiting
• Start date: March 28, 2018
• Est. completion date: June 1, 2020

Study information

• Verified date: February 2020
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

It is well known that dietary protein is a powerful transient stimulator of the muscle protein synthetic rate (MPS) whereby changes in MPS in response to feeding may be regulated by specific downstream target proteins of mammalian target of rapamycin signaling, such as S6K1, rpS6, and eIF2B. A meal deficient in protein, however, does not increase the rate of MPS because a rise in the bioavailability of amino acids does not occur. In addition, the source of dietary proteins has been shown to impact postprandial blood levels of amino acids. The concept that certain types of proteins are "fast acting" or "slow acting" has been shown to affect the postprandial profile of amino acids appearing in the systemic circulation. Native whey and micellar casein are both dairy proteins that contain a similar amount of essential (EAA), but blood EAA levels increase faster and to a higher level after the consumption of whey protein. Differences in gastric emptying, digestion and absorption kinetics between micellar casein and native whey are the underlying factors. Nonetheless, micellar casein protein has been shown to protract MPS in humans. Despite the significant amount of information gained with respect to both of these protein sources, the effects of combinatorial formulations on the postprandial profile of amino acids appearing in the blood is less well known. The purpose of the present study is to determine post-ingestion aminoacidemia, glycemia, and insulinemia from a specially formulated dairy protein blend.

Description:

Experimental approach:

8 participants will be included in this study. Each participant will consume the supplement only once in a randomized fashion during three separate visits and there will be approximately 1 week between each visit.

Standardized meal:

Participants will be provided a standardized diet one day prior to experimentation. When performing research involving human metabolism it is important that the participants be tested in a weight-stable state. Therefore, the investigators will estimate the participants resting energy expenditure using a widely reference prediction formula, known as the Harris-Benedict equation. This formula takes into account gender, body mass, height, age, and self-reported activity level. Once resting energy expenditure is calculated the investigators will provide each participant with a pre-packaged standardized diet for the day prior to the experiment that is designed to ensure a sufficient energy balance.

Dual Energy X-Ray Absorptiometry (DXA) Scans:

DXA scans will be used to determine the participants body composition. The DXA procedures use a small amount of radiation to determine how much fat, bone, and lean mass the participants have in their body. The procedure takes approximately seven minutes and involves the participants lying still on an open bed while the sensor passes over the participants body.

Arterialized blood sampling:

All blood sampling will be achieved through an intravenous indwelling cannula. This method provides the least trauma to the participant when repeated blood sampling is required and is convenient for the investigators. In theory, repeated needle sticks may stress the participant thereby increasing sympathetic nervous system activity, thus causing changes in metabolism. Additionally, another potential drawback from venous blood sampling is the influence by regional tissue specific metabolism, thereby making it difficult to interpret whole-body metabolism on the basis of metabolites measured in venous blood. Therefore, arterial blood sampling is deemed the ideal method for metabolic studies. Arterial cannulation, however, may be unethical for research purposes due to increased risk of complications, such as damage to the arterial wall, thrombosis, and clot formation, all of which may cause death. Arterializing the blood being sampled can be achieved through heating either the superficial antecubital vein or dorsal hand vein with a heating blanket or specialized heat box. By doing so, blood flow increases as a result of vasodilatation of vessels in the arms skeletal musculature, as well as arteriovenous anastomoses in skin. Due to the increased blood flow and negligible muscle mass at the hand and elbow, results in venous blood being similar in composition to an arterial sample. This method is a widely used surrogate for safe direct arterial blood sampling. Once arterialized blood samples are obtained they will be preserved and used in analyses. The investigators will utilize heating blankets (Theratherm Large Digital Moist Heat Pad [14" x 27"]) to arterialize the blood samples and an infrared thermometer (Nubee, NUB8380) to determine the skin temperature (45-68∘C) prior to drawing the participant's blood.

Per-protocol conditions will include:

Consumption of a standardized meal the evening prior to each trial and consistent exercise/activity 2d before each trial There will be ~1wk between trials (washout periods) Blood samples will be analyzed for plasma amino acids, glucose, and insulin.

Experimental Interventions (randomized order):

1. Participants will consume a Low Protein Containing Breakfast (10% of the Acceptable Macronutrient Distribution Range according to the Food and Nutrition Board of the Institute of Medicine) and 2 hours later the participants will consume 17g of a leucine enriched whey protein- hydrolyzed whey protein-micellar casein blend (50:43:7 whey:hydrolyzed-whey:casein) containing 600 IU Vitamin D and 3.5g leucine

2. Participants will consume a High Protein Containing Breakfast (25% of the Acceptable Macronutrient Distribution Range according to the Food and Nutrition Board of the Institute of Medicine)

3. Participants will consume a Low Protein Containing Breakfast (10% of the Acceptable Macronutrient Distribution Range according to the Food and Nutrition Board of the Institute of Medicine)

Proteins were provided by Covance Laboratories, Inc. owned by Eurofins.

The whey protein and micellar casein are milk proteins derived from cow's milk. The participants will consume the 17g of protein contained in a semi-solid bar equal to ∼40g, which is the size of a typical sports recovery bar.

Sample size and data analyses:

The sample size was determined by a statistical power analysis (G*Power 3.1 software, version 3.1.9, 2014) that revealed a large effect size. This study was powered on the basis of previous studies. Thus, a total of 8 (n = 8/group) participants will be used in analyses. See Below:

Analysis: A priori: Compute required sample size ANOVA: Repeated measures, within-between interaction Input Effect size f = 0.5 α err prob = 0.05 Power (1-β err prob) = 0.95 Number of groups = 3 Number of measurements = 14 Corr. Among rep. measures = 0.5 Nonsphericity correction ε = 1 Output Noncentrality parameter ƛ = 63 Critical F = 1.6380186 Numerator df = 26 Denominator df = 78 Total sample = 9 Actual power = 0.997

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 8
• Est. completion date: June 1, 2020
• Est. primary completion date: December 1, 2019
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• 8 participants will be included in this study. Each participant will consume the supplement only once in a randomized fashion during one of three separate visits and there will be approximately 1 week between each visit. In order to participate in this study, each participant must be male or female, 65 years or older (inclusive) and cannot be a smoker or user of tobacco products.

Exclusion Criteria:

• The exclusion requirements for this study include the following conditions:

• Take any analgesic or anti-inflammatory drugs(s), prescription or non-prescription, chronically will be excluded. However, a washout period of 4 weeks will be suitable for participation.

• A history of neuromuscular problems or muscle and/or bone wasting diseases

• Any acute or chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, insulin- or non-insulin dependent diabetes or other metabolic disorders-all ascertained through medical history screening questionnaires

• Use medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications)

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• Enriched Protein®
This product contains high quality bovine milk proteins enriched with additional leucine.

Locations

Country	Name	City	State
Canada	Exercise Metabolism Research Laboratory, McMaster Univeristy	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (14)

Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrère B. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14930-5. — View Citation

Burd NA, West DW, Staples AW, Atherton PJ, Baker JM, Moore DR, Holwerda AM, Parise G, Rennie MJ, Baker SK, Phillips SM. Low-load high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in youn — View Citation

Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ, Mitchell CJ, Moore DR, Stellingwerff T, Breuille D, Offord EA, Baker SK, Phillips SM. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in y — View Citation

Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following re — View Citation

Copeland KC, Kenney FA, Nair KS. Heated dorsal hand vein sampling for metabolic studies: a reappraisal. Am J Physiol. 1992 Nov;263(5):E1010-4. doi: 10.1152/ajpendo.1992.263.5.E1010. — View Citation

Douglas CC, Lawrence JC, Bush NC, Oster RA, Gower BA, Darnell BE. Ability of the Harris Benedict formula to predict energy requirements differs with weight history and ethnicity. Nutr Res. 2007 Apr;27(4):194-199. — View Citation

Green JH, Ellis FR, Shallcross TM, Bramley PN. Invalidity of hand heating as a method to arterialize venous blood. Clin Chem. 1990 May;36(5):719-22. — View Citation

Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006 Aug;29 — View Citation

Koopman R, Crombach N, Gijsen AP, Walrand S, Fauquant J, Kies AK, Lemosquet S, Saris WH, Boirie Y, van Loon LJ. Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein — View Citation

Koopman R, Walrand S, Beelen M, Gijsen AP, Kies AK, Boirie Y, Saris WH, van Loon LJ. Dietary protein digestion and absorption rates and the subsequent postprandial muscle protein synthetic response do not differ between young and elderly men. J Nutr. 2009 — View Citation

Luiking YC, Abrahamse E, Ludwig T, Boirie Y, Verlaan S. Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behaviour: A randomized trial. Clin Nutr. 2016 Feb;35(1):48-58. do — View Citation

Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr. 2009 Jan;89(1):161-8. doi — View Citation

Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol (1985). 2009 Sep;10 — View Citation

Tipton KD, Elliott TA, Cree MG, Wolf SE, Sanford AP, Wolfe RR. Ingestion of casein and whey proteins result in muscle anabolism after resistance exercise. Med Sci Sports Exerc. 2004 Dec;36(12):2073-81. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Easy-fast amino acid sample testing kit for gas chromatography mass spectrometry	plasma amino acid concentrations	375 minutes
Secondary	Hexokinase/G-6-PDH methodology	plasma glucose concentrations	375 minutes
Secondary	Chemiluminescent Microparticle Immunoassay	plasma insulin concentrations	375 minutes
Secondary	Visual Analog Scale Questionnaires for food sensory perception desire to eat	Units on a 100mm Paper Scale, 0mm = lowest score and 100mm = highest score	Average score across 13 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for hunger	Units on a 100mm Paper Scale, 0mm = lowest score and 100mm = highest score	Average score across 13 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for fullness	Units on a 100mm Paper Scale, 0mm = lowest score and 100mm = highest score	Average score across 13 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for thirst	Units on a 100mm Paper Scale, 0mm = lowest score and 100mm = highest score	Average score across 13 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for how much food could be eaten	Units on a 100mm Paper Scale, 0mm = lowest score and 100mm = highest score	Average score across 13 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for liking or disliking of food	Units on a 100mm Paper Scale, 0mm = worst score and 100mm = best score	Average score across 13 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for visual appeal	Units on a 100mm Paper Scale, 0mm = worst score and 100mm = best score	Average score across 2 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for smell	Units on a 100mm Paper Scale, 0mm = worst score and 100mm = best score	Average score across 2 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for taste	Units on a 100mm Paper Scale, 0mm = worst score and 100mm = best score	Average score across 2 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for aftertaste	Units on a 100mm Paper Scale, 0mm = worst score and 100mm = best score	Average score across 2 measurements
Secondary	Visual Analog Scale Questionnaires for food sensory perception for pleasantness	Units on a 100mm Paper Scale, 0mm = worst score and 100mm = best score	Average score across 2 measurements
Secondary	Height in meters	Stadiometer	One measurement at baseline
Secondary	Weight in kilograms	Physician scale	One measurement at baseline