Fate of Nutrient-Derived Amino Acids, FONDAA (FONDAA)

Fate of Nutrient-Derived Amino Acids: Influence of Habituated Levels of Daily Dietary Protein Intake on Protein Utilization

12 elderly (65-70 years of age) male subjects will be included and complete a double blinded cross-over study. They will be habituated for 21 days to either low or high protein intake (below 0.8 g/kg or above 1.5 g/kg, respectively). Following a 45 day washout period they will switch to the alternate group. At the end of each habituation period, the investigators will measure the appearance of labelled amino acids from milk proteins.

Study Overview

• Status: Completed
• Conditions: Dietary Protein; Protein Utilization
• Intervention / Treatment: Dietary supplement: Meal serving at high dietary protein; Dietary supplement: Meal serving; Dietary supplement: Meal serving at low dietary protein

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Institute of Sports Medicine Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 70 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Exclusion Criteria:

• Hyperlipidemia
• Hypertension

Inclusion Criteria:

• Males age 65-70
• Independently dwelling
• Without any major health issues (blood pressure, cholesterol and lipid profile will be measured and evaluated by a physician)
• Non-diabetic
• No organ disease
• No back pain
• Not regularly take any prescription drugs or dietary supplements, which can influence muscle protein synthesis
• Alcohol intake below 21 units pr. week
• No known arthrosclerosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Meal serving at high dietary protein; Test the handling of meal-served protein when habituated to high dietary protein at an amount above 1.5 g protein/kg/day	Dietary supplement: Meal serving at high dietary protein; Participants are habituated to a high level of dietary protein intake for 21 days.; Dietary supplement: Meal serving; To investigate impact of habituated protein level
Active Comparator: Meal serving at low dietary protein; Test the handling of meal-served protein when habituated to high dietary protein at an amount below 0.8 g protein/kg/day	Dietary supplement: Meal serving; To investigate impact of habituated protein level; Dietary supplement: Meal serving at low dietary protein; Participants are habituated to a low level of dietary protein intake for 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abundance of milk protein-bound amino acid labels in blood protein.	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: After intake of milk proteins at time 0 (zero) the quantity of intrinsic labels D5-phe from whey and 15N-phe from casein will be measured in liver-synthesized blood protein at 240 min.	Baseline to 240 min postprandial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abundance of milk protein-bound amino acid labels in myofibrillar protein.	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: After intake of milk proteins at time 0 (zero) the quantity of intrinsic labels D5-phe from whey and 15N-phe from casein will be measured in myofibrillar protein at 240 min.	Baseline to 240 min postprandial
Leg phenylalanine rate of disappearance and appearance, net balance.	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: From arterial and femoral venous blood samples obtained at baseline, 30, 60, 90, 120, 150, 180, 240 min phenylalanine tracer enrichments and concentrations as well as plasma flow will be measured.	Baseline to 240 min postprandial
First pass splanchnic extraction of dietary protein-derived labeled phenylalanine.	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: From hepatic venous blood samples obtained at baseline, 30, 60, 90, 120, 150, 180, 240 min phenylalanine tracer enrichments and concentrations as well as plasma flow will be measured. Knowing the amount of ingested protein and labeled phenylalanine we can calculate the first pass splanchnic amino acid extraction.	Baseline to 240 min postprandial
Whole body phenylalanine rate of disappearance and appearance, net balance.	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: From blood samples obtained at baseline, 30, 60, 90, 120, 150, 180, 240 min phenylalanine tracer enrichments will be measured.	Baseline to 240 min postprandial
The myofibrillar protein fractional synthesis rate	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: From muscle biopsies obtained at baseline, 60 and 240 min the abundance of phenylalanine tracer bound in the myofibrillar proteins will be measured and the fractional synthesis rate will be measured within the first from baseline to 60 min and 240 min as well as from 60-240 min postprandial.	Baseline to 240 min postprandial
Response of expression of proteins involved in muscle protein turnover	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: From baseline to 60 and 240 min after intake of the standardized meal after 21 days of habituation to either a high or a low dietary protein intake expression of signalling proteins related to protein turnover in the muscle will be measured by use of western blotting.	Baseline, 60 min and 240 min postprandial
Urea production.	Related to the trials conducted after 21 days of habituation to either high or low protein in the diet: From blood samples obtained at baseline, 30, 60, 90, 120, 150, 180, 240 min urea tracer enrichments and concentrations will be measured. With this, and flow measurements, we can determine the rate of urea production.	Baseline to 240 min postprandial
Nitrogen and creatinine excreted in urine	Related to the adaptation to the 21 day habituation period to either high or low protein in the diet as well as the response to the standardized trial meal: Nitrogen and creatinine content is measured in urine is collected for the last 24 h of the 21 day habituation period, as well as during the 240 min trial day and the remaining 20 hours of the trial day.	21 days post intervention, 240 min postprandial and 24 hours post the day 21 trial day
Fecal microbiota composition	Related to the adaptation to the 21 day habituation period to either high or low protein in the diet as well as the response to the standardized trial meal: The microbiota compositions, will be measured in fecal samples collected before the 21 day habituation period, after the 21 day habituation periode, as well as after the 240 min trial day	Change from pre-intervention to 21 days and 22 days (21 intervention days habituation and the standardized trial meal on day 21)
Adaptation of expression of proteins involved in muscle protein turnover	Related to the adaptation to the 21 day habituation period to either high or low protein in the diet: Biopsies taken following the two 21 day habituation period will, by use of western blotting, be analysed for expression of signalling proteins involved in muscle protein turnover.	After 21 days of habituation to either a high or a low dietary protein intake.

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Investigators: Principal Investigator: Grith Højfeldt, M.Sc., Bispebjerg Hospital; Principal Investigator: Lars Holm, Ph.D., Bispebjerg Hospital

Publications and helpful links

General Publications

• Hojfeldt G, Bulow J, Agergaard J, Asmar A, Schjerling P, Simonsen L, Bulow J, van Hall G, Holm L. Impact of habituated dietary protein intake on fasting and postprandial whole-body protein turnover and splanchnic amino acid metabolism in elderly men: a randomized, controlled, crossover trial. Am J Clin Nutr. 2020 Dec 10;112(6):1468-1484. doi: 10.1093/ajcn/nqaa201.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): February 8, 2018
• Study Completion (Actual): February 8, 2018

Study Registration Dates

• First Submitted: October 22, 2015
• First Submitted That Met QC Criteria: October 26, 2015
• First Posted (Estimate): October 27, 2015

Study Record Updates

• Last Update Posted (Actual): March 5, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Amino acid; Required dietary protein; Splanchnic extraction
• Other Study ID Numbers: BBH122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided