The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Epithelium

Protein Malabsorption Clinical Trial

— GutFeeding  

Official title:

The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Mucosal Protein in Young and Older Males

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06091852
• Other study ID #: METC23-011
• Status: Completed
• Phase: N/A
• Start date: July 24, 2023
• Est. completion date: April 5, 2024

Study information

• Verified date: October 2023
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Rationale: Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion.This anabolic resistance may be related to decreased postprandial amino acid release in the circulation, due to greater amino acid extraction by splanchnic tissues in older individuals. It has been suggested that extracted amino acids are utilized by intestinal epithelial cells for cell proliferation, generating new cells to maintain healthy mucosa. So far, there is no evidence that dietary protein-derived amino acids are taken up and incorporated in intestinal mucosal protein in vivo in humans. Furthermore, there is no evidence that this process is impacted by age.

Objective: To assess the postprandial incorporation of dietary protein-derived amino acids in intestinal mucosal protein in healthy young and older males.

Study design: Cross-sectional, non-therapeutic intervention study design

Study population: 5 healthy, non-obese (BMI 18.5-30kg/m2) young adult males (age: 18-35y inclusive) and 5 community dwelling older males (age: 67+y).

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.

Main study parameters/endpoints: The primary study outcome is the postprandial (0-5h) incorporation of dietary protein-derived amino acids in duodenal mucosal protein following the ingestion of 20g intrinsically labelled milk protein. Secondary study parameters include postprandial plasma availability of dietary protein-derived amino acids and fractional duodenal mucosal protein synthetic rate.

Description:

Skeletal muscle tissue is in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates, with a turnover rate of 1-2% per day. It has been well established that protein ingestion is a major anabolic stimulus for muscle protein synthesis. Dietary protein ingestion provides amino acids that stimulate protein synthesis by both functioning as substrate and as signalling molecules that upregulate anabolic pathways.

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. Following protein ingestion, protein is cleaved into small peptides and amino acids by digestive enzymes. Subsequently, these amino acids are absorbed across the intestinal mucosa by various membrane-bound transporters. The majority of dietary protein derived amino acids is released into the systemic circulation and transported and taken up by various peripheral tissues in the postprandial phase. However, 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, termed first-pass splanchnic extraction. Previous work in our laboratory has estimated that up to 40% of the protein derived amino acids are taken up and incorporated in the intestinal tract and liver tissues. The intestine is the most highly regenerative organ in the human body, regenerating its epithelium every 3 to 5 days. It has been suggested that the absorbed amino acids are utilized by epithelial cells for rapid cell proliferation, generating new cells to maintain healthy mucosa. Human studies on the incorporation of dietary protein-derived amino acids in intestinal mucosal protein have not been performed. Therefore, the aim of the present explorative in vivo study is to assess, for the first time, the incorporation of dietary protein-derived amino acids in duodenal mucosal protein in humans, and the systemic availability of dietary protein-derived amino acids.

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 impairments in protein digestion and amino acid absorption, and greater first-pass splanchnic amino acid extraction in older individuals. Whether dietary protein-derived amino acid incorporation in intestinal mucosal protein is increased with aging remains to be established. Therefore, the current study will use the data on incorporation of dietary protein-derived amino acids in duodenal mucosal protein and postprandial amino acid plasma availability obtained in young and older individuals to evaluate potential age-related differences.

Two primary hypotheses will be tested:

1. It is hypothesized that part of the absorbed amino acids will be directly incorporated in duodenal epithelium within 5 hours after protein ingestion.

2. It is hypothesized that the extent of postprandial incorporation of dietary protein derived amino acids in duodenal epithelium will be greater in older compared to young males.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: April 5, 2024
• Est. primary completion date: April 5, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malabsorption Syndromes
• Protein Malabsorption

Intervention

Dietary Supplement:
• Intrinsically labelled milk protein
20 grams of protein dissolved in 500 mL of water

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center+	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	FrieslandCampina

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Age in years	Reported by participants	Baseline
Other	Body weight in kg	Scale	Baseline
Other	Height in m	Stadiometer	Baseline
Other	BMI in kg/m2	Calculated from height and body weight	Baseline
Other	Skeletal muscle mass	Bioelectrical impedance analysis	Baseline
Other	Fat mass	Bioelectrical impedance analysis	Baseline
Other	Dietary macronutrient intake	Assessed by written dietary intake records	2 days prior to experimental trial day
Other	Systolic blood pressure in mmHg	Electrical sphygmomanometer	Baseline
Other	Diastolic blood pressure in mmHg	Electrical sphygmomanometer	Baseline
Primary	Postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein	Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE)	0-5 hours
Primary	Impact of age on postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein	Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE) in young and older adults	0-5 hours
Secondary	Postprandial plasma amino acid concentrations	Appearance of milk protein-derived amino acids in plasma over the full assessment period (5 h), as determined using stable isotope tracer methodology	0-5 hours
Secondary	Fractional duodenal mucosal protein synthetic rate	Mucosal protein synthesis rates are calculated using L-ring-2H5-phenylalanine tracer and provided as 1 integrated value over the specified timeframe using plasma as precursor	0-5 hours
Secondary	Fractional muscle protein synthetic rate	Muscle protein synthesis rates are calculated using L-ring-2H5-phenylalanine tracer and provided as 1 integrated value over the specified timeframe using plasma as precursor	0-5 hours
Secondary	Fecal [1-13C]-phenylalanine enrichments (expressed as MPE)	Fecal protein excretion, assessed by fecal [1-13C]-phenylalanine enrichments (expressed as MPE)	Fecal sample of first feces after endoscopy
Secondary	Fecal nitrogen content	Fecal protein excretion, assessed by fecal nitrogen content	Fecal sample of first feces after endoscopy
Secondary	Fecal microbial metabolites	Microbial metabolites, including short-chain fatty acids, assessed by analyzing fecal samples	Fecal sample of first feces after endoscopy
Secondary	Plasma glucose concentrations	Plasma glucose concentrations	0-5 hours
Secondary	Plasma insulin concentrations	Plasma insulin concentrations	0-5 hours