The Impact of Milk Protein Glycation on Protein Digestion and Absorption
Condition: Protein Digestion & Absorption
Study type: Interventional

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.
    

Intervention name(s): Low glycated milk protein; High glycated milk protein
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 40 grams of protein dissolved in 600 mL of water; 40 grams of protein dissolved in 600 mL of water
Intervention MeSH terms: Caseins
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double blind, randomized, cross-over intervention study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Protein digestion; Protein glycation; Processing