Impact of Carbohydrate Co-ingestion on the Post-prandial Anabolic Response of Protein in Young and Elderly Men
Condition: Sarcopenia
MeSH terms: Sarcopenia
Study type: Interventional

Summary: 
      Rationale: Age related muscle loss (sarcopenia) is assumed to be related to the impaired
      postprandial muscle protein synthetic response to protein and/or amino acid administration in
      the elderly vs the young. Co-ingestion of carbohydrate increases post-prandial insulin
      secretion. Insulin affects skeletal muscle blood flow and may therefore affect substrate
      availability and postprandial muscle protein synthesis. However, it is unclear whether the
      response to the combined intake of protein and carbohydrates is different in elderly compared
      to young subjects.

      Hypothesis: Adding carbohydrate to a bolus of protein represents an effective strategy to
      overcome the impaired postprandial muscle protein synthesis in the elderly.

      Objective: The primary objective of the study is to investigate whether carbohydrate
      co-ingestion augments the in vivo postprandial muscle protein synthetic response after
      protein ingestion and whether this response is different between young and elderly subjects.
      The secondary objective of the study is to assess the effect of carbohydrate co-ingestion on
      insulin levels and microvascular perfusion in young and elderly subjects.

      Intervention: The intervention consists of a single test day during which the subjects will
      receive a drink containing 20 gram intrinsically labelled casein with or without 60 gram
      carbohydrates. In addition, continuous intravenous tracer infusions of labeled amino acids
      will be administered. During the test day 18 plasma samples and 4 muscle biopsies will be
      collected over a period of 8½ h. Furthermore, muscle skeletal blood flow will be estimated
      using sidestream darkfield imaging (SDF) in sublingual position.
    

Detailed description: 
      With human aging, there is a gradual but progressive decline in skeletal muscle tissue, also
      known as sarcopenia . Sarcopenia is accompanied by a reduced physical performance, the loss
      of functional capacity, increased risk of falling and increased likelihood of developing
      chronic metabolic diseases, such as type 2 diabetes and obesity. Eventually this also results
      in increased hospitalisation and institutionalization of elderly in nursing homes, and high
      health care costs. Therefore, it is important to investigate approaches to diminish the loss
      of skeletal muscle mass during aging. To preserve muscle mass, protein intake is important,
      because it provides the building blocks for muscle tissue: amino acids. Since basal muscle
      protein synthesis rates do not seem to differ between young and elderly, currently many
      research groups focus on postprandial muscle protein synthesis. Skeletal muscle protein
      synthesis has been shown to be highly dependent on protein intake. However, recent data
      indicate that the muscle protein synthetic response to protein intake is attenuated in the
      elderly. A blunted postprandial muscle protein synthetic response over a prolonged period
      might result in diminished muscle protein accretion and could eventually contribute to
      sarcopenia.

      The anabolic response to protein intake appears to be mainly mediated by an elevation of
      plasma essential amino acids. In addition, ingestion of carbohydrate leads to an attenuation
      of muscle protein breakdown by virtue of an elevation in plasma insulin, further promoting
      positive net protein balance. This is mediated by insulin's known action of increasing muscle
      blood flow and thereby augmenting muscle substrate delivery, which may lead to further
      stimulation of muscle protein synthesis. It has been shown that there is an insulin
      resistance with respect to muscle protein anabolism in elderly compared to young subjects
      during conditions of high plasma amino acid and insulin availability. This suggests that the
      reduced ability of insulin to augment muscle microvascular perfusion decreases the amino acid
      stimulus.

      In the present study the investigators will assess the effect of a single meal-like amount of
      intact protein with or without carbohydrates on post-prandial muscle protein synthesis in the
      elderly (70-85 y) compared to the young (18 - 30 y). Furthermore, the investigators are going
      to investigate whether the muscle protein synthetic response is associated with an increase
      in the microvascular perfusion after ingestion of the meal using Sidestream Dark Field (SDF)
      imaging. SDF measurements will be taken in de oral cavity underneath the tongue, since this
      area is easily accessible and is representative for microvascular perfusion. To be able to
      measure the effect of protein ingestion on muscle protein synthesis the investigators will
      use intrinsically labelled casein. This allows us to determine the true incorporation of
      amino acids from the ingested, intact casein into the muscle, taken into account the
      influence of digestion and absorption processes of a whole protein. Intrinsically labelled
      milk proteins were derived from milk that has been collected from cows that were infused with
      L-[1-13C] phenylalanine.

      The following hypotheses will be investigated:

        1. The combined intake of protein and carbohydrates augments post-prandial muscle protein
           synthesis in the elderly, but not in the young subjects.

        2. The increased insulin production following the combined intake of protein and
           carbohydrates results in an increased microvascular perfusion that is related to the
           post-prandial muscle protein synthetic response.
    

Intervention name(s): Protein; Protein + carbohydrate
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Subjects will receive a drink containing 20 gram intrinsically labelled casein.
Half of the subject are young males (YOUNG)(age between 18 and 35 y) and half of the subjects are elderly males (OLD)(age between 70 and 85 y).; subjects will receive a drink containing 20 gram intrinsically labelled casein plus 60 gram carbohydrates.
Half of the subject are young males (YOUNG)(age between 18 and 35 y) and half of the subjects are elderly males (OLD)(age between 70 and 85 y).
Other intervention name(s): Intrinsically labelled casein; Casein plus dextrose monohydrate and maltodextrin
Intervention MeSH terms: Caseins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: muscle metabolism; intrinsically labeled protein; protein synthesis; insulin; perfusion