The Impact of Milk Protein Glycation on Protein Digestion and Absorption (VerLys)

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

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.

Study Overview

• Status: Completed
• Conditions: Protein Digestion & Absorption
• Intervention / Treatment: Dietary supplement: Low glycated milk protein; Dietary supplement: High glycated milk protein

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Glenn van Lieshout, MSc; Phone Number: 0031433881617; Email: g.vanlieshout@maastrichtuniversity.nl
• Study Contact Backup: Name: Luc van Loon, Prof.; Phone Number: 0031 43 388 1397; Email: l.vanloon@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University Medical Center+

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low glycated milk protein; 40 grams of low glycated milk protein, blocked lysine level ~5%	Dietary supplement: Low glycated milk protein; 40 grams of protein dissolved in 600 mL of water
Experimental: High glycated milk protein; 40 grams of high glycated milk protein, blocked lysine level ~50%	Dietary supplement: High glycated milk protein; 40 grams of protein dissolved in 600 mL of water

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age	Age in years	Baseline
Body weight	Body weight in kg	Baseline
Body length	Body length in cm	Baseline
BMI	BMI in kg/m^2, calculated from weight and length	Baseline
Fat mass	Fat mass in kg.	Baseline
Fat percentage	Fat mass in fat percentage, calculated using fat mass & body weight in kg.	Baseline
Lean body mass	Lean body mass in kg.	Baseline

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: FrieslandCampina

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Actual): June 23, 2023
• Study Completion (Actual): June 23, 2023

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Protein digestion; Protein glycation; Processing
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: METC 22-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No