The Impact of Milk Protein Glycation on Protein Digestion and Absorption

Study Overview
=================
Brief Summary
-----------------
Rationale: Protein intake is an essential stimulus for muscle protein anabolism. The muscle protein synthetic response to protein ingestion is mainly determined by the post-prandial plasma amino acid response. Milk protein often undergoes glycation during commonly applied milk processing procedures (Maillard reaction). We have previously shown that glycated protein results in lower postprandial amino acid levels. The level of protein glycation in processed dairy products might therefore be an important modulator of the overall protein quality of a product, and its ability to stimulate protein metabolism. However, it has not yet been investigated if the glycation level of dietary protein modulates its appearance in plasma as amino acids. Objective: To compare the appearance of dietary protein-derived amino acids in plasma after ingestion of a milk protein powder with different levels of protein glycation in healthy young men. Study design: Double blinded, randomized cross-over study. Study population: 15 healthy young males, aged 18-35 years. Intervention (if applicable): All subjects will perform two experiments in a double-blinded, randomized order: ingest 40 g of milk protein with 5% glycation level in 600 mL water, or 40 g of milk protein with 50% glycation level in 600 mL water. After ingestion, blood samples will be taken at regular intervals during a 6 hour period. Main study parameters/endpoints: The primary endpoint will be the appearance of milk protein-derived amino acids in plasma over the full assessment period (6 h), as determined using stable isotope tracer methodology.

Detailed Description
-----------------
Proteins are mainly required as building blocks for muscle maintenance and muscle growth. To supply these building blocks for growth and development, proteins need to be well digested, and absorbed in the circulation. Processing of milk to produce dairy products, such as milk protein powders, may affect protein quality. Heat processes can impact native protein structure, for example by inducing protein denaturation and aggregation. In addition, reducing sugars such as lactose can react with the amino group of amino acids, known as the Maillard reaction or protein glycation. Glycation levels in milk protein powders can range from 5-50%, depending on factors such as water content and storage temperature. Several in vitro and animal studies have shown that protein glycation decreases protein digestibility. In addition, we have recently demonstrated that protein glycation reduces post-prandial amino acid availability in humans. This reduced postprandial amino acid availability could mostly be attributed to a reduction in postprandial availability of the essential amino acid lysine. The lower post-prandial availability of amino acids following ingestion of protein with a high glycation level suggests an impaired digestion and absorption of glycated dietary protein. Therefore, to test whether ingestion of a high glycated milk protein results in a lower appearance of dietary protein-derived amino acids, a human trial has been designed. Subjects will consume a low or high glycated milk protein drink, where after several blood samples will be taken to assess the appearance of dietary protein-derived amino acids over time by using a continuous amino acid tracer infusion. The low and high glycated protein drinks reflect the lower and upper range of protein glycation reported in dairy protein products. We hypothesize that protein glycation attenuates the appearance of dietary protein-derived amino acids in plasma.

Official Title
-----------------
The Impact of Milk Protein Glycation on Protein Digestion and Absorption in Healthy Young Men

Conditions
-----------------
Protein Digestion & Absorption

Intervention / Treatment
-----------------
* Dietary Supplement: Low glycated milk protein
* Dietary Supplement: High glycated milk protein


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males Aged between 18-35 years Healthy, recreationally active (participating in recreational sports activities ≥ 1 and ≤ 6 h per week, with a maximum of 2 h resistance-type exercise) 18.5 ≤ BMI ≤ 30 kg/m2 No physical limitations (i.e. able to perform all activities associated with daily living in an independent manner). Exclusion Criteria: Smoking Lactose intolerant or allergies to milk proteins Musculoskeletal disorders Metabolic disorders Use of any medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescribed acne medications). Chronic use of gastric acid suppressing medication or anti-coagulants Unstable weight over the last three months Diagnosed GI tract disorders or diseases Blood donation in the past 2 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double blind, randomized, cross-over intervention study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low glycated milk protein<br>40 grams of low glycated milk protein, blocked lysine level  5% | Dietary Supplement: Low glycated milk protein<br>* 40 grams of protein dissolved in 600 mL of water<br>|
| Experimental: High glycated milk protein<br>40 grams of high glycated milk protein, blocked lysine level  50% | Dietary Supplement: High glycated milk protein<br>* 40 grams of protein dissolved in 600 mL of water<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma appearance of dietary amino acids | Appearance of milk protein-derived amino acids in plasma over the full assessment period (6 h), as determined using stable isotope tracer methodology | 0-6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole-body protein kinetics | total rate of appearance, exogenous rate of appearance, endogenous rate of appearance, rate of disappearance | 0-6 hours | 
| Whole body protein metabolism | Protein synthesis, breakdown, oxidation, and net balance | 0-6 hours | 
| Peak plasma lysine concentration | Maximum plasma lysine concentration | 0-6 hours | 
| Overall plasma amino acid responses | Plasma amino acid concentration before and after intake of the drink | 0-6 hours | 
| Plasma glucose concentrations | Plasma glucose concentrations | 0-6 hours | 
| Plasma insulin concentrations | Plasma insulin concentrations | 0-6 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Protein digestion, Protein glycation, Processing