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CompletedNCT01576848PRO-CARBUpdated Apr 13, 2012

Impact of Carbohydrate Co-ingestion on the Post-prandial Anabolic Response of Protein in Young and Elderly Men

An interventional study of Protein and Protein + carbohydrate in Sarcopenia, sponsored by Maastricht University Medical Center. Completed at 1 site in Netherlands. Open to male participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2012-04-13.

Sponsored by Maastricht University Medical Center · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
48
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
Male
01

Study 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.

Read the 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.
02

Conditions studied

  • Sarcopenia

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Keywords

  • muscle metabolism
  • intrinsically labeled protein
  • protein synthesis
  • insulin
  • perfusion
03

In context

Sarcopenia

1,208 studies on the registry are indexed under Sarcopenia; 402 are open to participants now.

This study's enrollment of 48 is below the median of 60 across 775 interventional studies indexed under Sarcopenia.

Browse Sarcopenia studies →

Lead sponsor

Maastricht University Medical Center is the lead sponsor of 835 studies on the registry; 122 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  • Males
  • Age 70-85 years or Age 18-30 years
  • BMI \< 30 kg∙m2

Exclusion criteria

Exclusion criteria:

  • Diabetes
  • HbA1c > 7.0%
  • Obesity (BMI > 30 kg/m2)
  • Diagnosed impaired renal or liver function
  • All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g. arthrosis, arthritis, spasticity/rigidity, all neurological disorders and paralysis).
  • Hypertension (according to WHO criteria) (36)
  • Use of anticoagulants, blood diseases, allergy for lidocain
  • Use of NSAIDs and acetylsalicylic acid
  • Use of gastric acid inhibitors
  • Patients suffering from PKU (Phenylketonuria)
  • Participation in any regular exercise program
  • Unstable body weight over the last 3 months
05

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
48 participants (actual)

Study arms

  • Experimental
    GROUP 1 (OLD-PRO)

    test drink contains intrinsically labeled protein alone

    Dietary Supplement: Protein

  • Experimental
    GROUP 2 (OLD-PRO/CARB)

    test drink contains intrinsically labeled protein and carbohydrate

    Dietary Supplement: Protein + carbohydrate

  • Experimental
    GROUP 3 (YOUNG-PRO)

    test drink contains intrinsically labeled protein alone

    Dietary Supplement: Protein

  • Experimental
    GROUP 4 (YOUNG-PRO/CARB)

    test drink contains intrinsically labeled protein and carbohydrate

    Dietary Supplement: Protein + carbohydrate

Interventions

  • Dietary supplementProtein

    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).

    Also known as: Intrinsically labelled casein

  • Dietary supplementProtein + carbohydrate

    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).

    Also known as: Casein plus dextrose monohydrate and maltodextrin

06

What researchers measure

Primary outcomes

  1. Change from fasted state in Muscle protein synthesis rate (expressed as Fractional Synthetic Rate, FSR) at different time points postprandial

    Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours

Secondary outcomes

  1. Change from fasted state in Whole body protein balance at different time ponits postprandial

    Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours

  2. Change from fasted state in Microvascular perfusion at different time points postprandial

    Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours

  3. Change from fasted state in Digestion kinetics of dietary intrinsically labeled protein at different time points postprandial

    Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours

  4. Change from fasted state in Absorption kinetics of dietary intrinsically labeled protein at different time points postprandial

    Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours

07

Study locations

1 site
  • Maastricht University
    Maastricht, Limburg 6200 MD, Netherlands
08

References and documents

Publications

  • Gorissen SHM, Trommelen J, Kouw IWK, Holwerda AM, Pennings B, Groen BBL, Wall BT, Churchward-Venne TA, Horstman AMH, Koopman R, Burd NA, Fuchs CJ, Dirks ML, Res PT, Senden JMG, Steijns JMJM, de Groot LCPGM, Verdijk LB, van Loon LJC. Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans. J Nutr. 2020 Aug 1;150(8):2041-2050. doi: 10.1093/jn/nxaa024. PubMed 32069356 ↗
  • Kouw IW, Gorissen SH, Burd NA, Cermak NM, Gijsen AP, van Kranenburg J, van Loon LJ. Postprandial Protein Handling Is Not Impaired in Type 2 Diabetes Patients When Compared With Normoglycemic Controls. J Clin Endocrinol Metab. 2015 Aug;100(8):3103-11. doi: 10.1210/jc.2015-1234. Epub 2015 Jun 2. PubMed 26037513 ↗
  • Gorissen SH, Burd NA, Hamer HM, Gijsen AP, Groen BB, van Loon LJ. Carbohydrate coingestion delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion. J Clin Endocrinol Metab. 2014 Jun;99(6):2250-8. doi: 10.1210/jc.2013-3970. Epub 2014 Mar 14. PubMed 24628553 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 13, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01576848
Lead sponsor
Maastricht University Medical Center
Responsible party
Henrike Hamer (MSc, Maastricht University Medical Center) — Principal investigator
First posted
Apr 13, 2012
Start date
Aug 2011
Primary completion
Mar 2012
Completion
Mar 2012
Last update
Apr 13, 2012

Study contacts

Luc JC van Loon, Prof.
principal investigator · Maastricht University

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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