To assess the postprandial incorporation of dietary protein derived amino acids in intestinal epithelium in healthy young and older males.
ID
Source
Brief title
Condition
- Protein and amino acid metabolism disorders NEC
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To assess the postprandial (0-5h) incorporation of dietary protein derived
amino acids in duodenal epithelium in healthy young and older males.
2. To investigate whether age affects the postprandial (0-5h) incorporation of
dietary protein derived amino acids in duodenal epithelium.
Secondary outcome
1. To assess the postprandial (0-5h) plasma availability of dietary protein
derived amino acids in healthy young and older males.
2. To assess postprandial (0-5h) fractional duodenal mucosal and muscle protein
synthetic rates in healthy young and older males.
Background summary
Skeletal muscle tissue is in a constant state of turnover, regulated by the
balance between tissue protein synthesis and breakdown rates. Protein ingestion
is a major anabolic stimulus for muscle protein synthesis. The anabolic
properties of dietary protein largely depend on the protein digestion and amino
acid absorption kinetics and subsequent increase in plasma amino acid
availability. A substantial part of the ingested protein does not become
available in the circulation. This part is either not (yet) digested and
absorbed, or the absorbed amino acids are taken up by splanchnic tissues, such
as the gut and liver, providing precursors for de novo tissue protein
synthesis. It has been suggested that these absorbed amino acids are utilized
by intestinal epithelial cells for rapid cell proliferation, generating new
cells to maintain healthy mucosa. However, human studies on the incorporation
of dietary protein derived amino acids in intestinal epithelium have not been
performed. Aging is accompanied by a blunted muscle protein synthetic response
to protein ingestion. This proposed anabolic resistance may be related to a
decreased postprandial amino acid release in the circulation, due to greater
first-pass splanchnic amino acid extraction in older individuals. Whether
dietary protein derived amino acid incorporation in intestinal epithelium is
increased with aging remains to be established.
Study objective
To assess the postprandial incorporation of dietary protein derived amino acids
in intestinal epithelium in healthy young and older males.
Study design
Cross-sectional, non-therapeutic intervention study design
Intervention
Continuous intravenous stable isotope amino acid tracer infusion will be
applied, in combination with oral ingestion of 20g intrinsically labelled milk
protein, with plasma, muscle and duodenal mucosa biopsy samples collected at
different time points throughout the experimental test day.
Study burden and risks
Participants will come to the laboratory for a total of two visits, comprising
of a screening visit (±2h) and one experimental test day (±8h). Two days prior
to the test day, participants will have to record their food intake and
physical activity performed. During these two days, participants are not
allowed to perform heavy physical exercise or drink alcohol. At the
experimental test day, they have to arrive in a fasted state.
The stable isotope amino acid tracers that will be infused intravenously are
produced according to GMP standards and are safe for human use. Intrinsically
labelled milk protein has recently been produced and has been provided by
Friesland Campina.
Insertion of catheters in a vein is comparable to normal blood draw and the
only risk is a small local hematoma. During the experimental test day, 15 blood
samples (150 mL total) will be obtained. The total amount of blood collected
during this study is less than half the amount of a blood donation and will be
completely restored in approximately one month.
Muscles biopsies will be obtained under local anaesthesia by an experienced
physician. The biopsies will be taken through a small (5mm) incision, and will
heal completely. The muscle biopsy may cause some minor discomfort comparable
to muscle soreness.
Duodenal biopsies will be obtained by an experienced gastroenterologist using
gastroduodenoscopy, which is considered a safe routine medical procedure with
low risk of complications.
There is no direct benefit for the participants except for their contribution
to the scientific knowledge of postprandial protein handling in the human gut
to optimize nutrition intervention strategies.
Universiteitssingel 50
Maastricht 6229ER
NL
Universiteitssingel 50
Maastricht 6229ER
NL
Listed location countries
Age
Inclusion criteria
- Male sex
- Aged 18-35 years or 67+ years
- Body mass index (BMI) between 18.5 and 30 kg/m2
Exclusion criteria
- History of cardiovascular, respiratory, gastrointestinal, urogenital,
neurological, psychiatric, dermatologic, musculoskeletal, metabolic, endocrine,
haematological, immunologic disorders, allergy, major surgery and/or laboratory
assessments which might limit participation in or completion of the study
protocol, interfere with the execution of the experiment, or potential
influence the study outcomes (to be decided by the principal investigator and
responsible physician)
- Major abdominal surgery interfering with gastrointestinal function (upon
judgement of the principal investigator and responsible physician)
- Use of medication which limit participation in or completion of the study
protocol, interferes with the execution of the experiment, or potential
influences the study outcomes (to be decided by the principal investigator and
responsible physician)
- Use of supplementation (i.e. vitamin, pre- and probiotic supplementation)
within 14 days prior to testing
- Administration of investigational drugs or participation in any scientific
intervention study in the 14 days prior to the study, which may interfere with
this study (upon judgement of the principal investigator and responsible
physician)
- Specific diet (e.g. vegetarian, vegan, gluten free, no diary) within the
study period
- Planning to lose weight during the study period
- Lactose intolerance
- Excessive alcohol consumption (defined as > 14 alcoholic consumptions per
week)
- Smoking
- Drug use
- Donated blood two months prior to the test day
- Recent (<1 year) participation in amino acid tracer
(L-[ring-2H5]-phenylalanine, L-[ring-2H3]-leucine, L-[ring-2H4]-lysine,
L-[ring-2H2]-tyrosine) or intrinsically labelled protein
([1-13C]-phenylalanine, [1-13C]-leucine, [1-13C]-lysine) studies
- No given permission to register participation in electronic patient file at
MUMC+ and to add records of gastroduodenoscopy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83740.068.23 |