Effects of Alpha-lactalbumin Intake on Metabolic and Cognitive Functions in Elderly

Effects of Alpha-lactalbumin on Metabolic and Cognitive Functions in Healthy Older Adults

Aging modifies the metabolic pathway of the neurotransmitter serotonin by reducing the synthesis rate and increasing the breakdown rate of serotonin, possibly related to the observed enhanced sensitivity of the serotonergic pathway. Since serotonin plays a prominent role in neuropsychological functions such as anxiety, mood and memory, the enhanced sensitivity of the serotonergic pathway in aging can probably explain the fact that elderly are more vulnerable to develop cognitive deficits and depressive symptoms.

Serotonin synthesis in brain is regulated by its precursor tryptophan (TRP). Because tryptophan is an essential amino acid, modifying the availability of tryptophan through dietary intake, can directly influence central serotonin metabolism and consequently affective and cognitive processes.

The aim of this study is to test the hypothesis that an acute intake of whey protein with high levels of TRP such as alpha-lactalbumin can stabilize the metabolism of serotonin and subsequently enhance metabolic and cognitive functions in healthy older adults. The acute effects of this dietary protein will be investigated in subjects with mild cognitive impairment (MCI), or dementia, compared to control subjects in order to examine whether healthy older subject with MCI benefit more from the intake of alpha-lactalbumin and/or whey. The investigators will investigate if this meal can optimize serotonin metabolism by elevating plasma TRP levels and plasma TRP appearance and enhance splanchnic TRP extraction. In addition, the effects on mood and cognitive functions will be examined.

Study Overview

• Status: Unknown
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Dietary supplement: Alpha-lactalbumin; Dietary supplement: Whey; Dietary supplement: Casein

Detailed Description

The study involves for all subjects 3 test days (approximately 8 hours each). On this test day the investigators will examine the acute effects of a protein meal. Subjects will receive a mixture of alpha-lactalbumin and/or whey and/or casein, carbohydrates and amino acid stable isotopes to investigate protein and amino acid kinetics (assigned to alpha-lactalbumin or whey or casein group on test day 1, then switch on test day 2 and 3). The subjects will receive these stable isotopes by infusion in their blood and by oral intake (e.g. simultaneously with protein meal). For study purposes, blood will be drawn approx. 25 times during 8 hours on the test day, altogether about 100-120 ml of blood will be drawn on the test day.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • College Station, Texas, United States, 77843
      • Texas A&M University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria subjects with dementia:

• Dementia diagnosis
• Ability to walk, sit down and stand up independently
• Age 55 years or older
• Ability to lie in supine or elevated position for 8 hours
• Willingness and ability to comply with the protocol, including:

Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Inclusion criteria healthy subjects:

• Healthy male or female according to the investigator's or appointed staff's judgment
• Ability to walk, sit down and stand up independently
• Age 55 years or older
• Ability to lie in supine or elevated position for 8 hours
• Willingness and ability to comply with the protocol, including:

Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Exclusion Criteria:

• Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
• Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
• Indication of severe cognitive impairment (MOCA score < 17)
• Established diagnosis of Insulin Dependent Diabetes Mellitus
• History of untreated metabolic disease(s) including hepatic or renal disorder
• Presence of acute illness or metabolically unstable chronic illness
• Presence of fever within the last 3 days
• Preplanned surgery of procedures that would interfere with the conduct of the study
• Any other condition according to the PI or study physician that would interfere with proper conduct of the study / safety of the patient
• Current alcohol or drug abuse
• Known allergy to milk or milk products
• Use of long-term oral corticosteroids or short course of oral corticosteroids 4 weeks preceding first test day
• Use of protein or amino acid containing nutritional supplements within 5 days of test day
• (Possible) pregnancy
• BMI of < 18.5 or ≥ 40 kg/m2
• Dietary or lifestyle characteristics: When during the period from enrollment to completion of the study (end of test day) any condition is developed, whether causing the subject to not meet inclusion criteria or to meet exclusion criteria, the subject will be excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy; healthy control subjects	Dietary supplement: Alpha-lactalbumin; Subjects will ingest the liquid meal containing alpha-lactalbumin and carbohydrates (0.6 g/kg FFM protein + 0.3 g/kg FFM carbohydrates).; Dietary supplement: Whey; commercially available whey protein; Dietary supplement: Casein; commercially available casein protein
Experimental: MCI; mild cognitive impariments	Dietary supplement: Alpha-lactalbumin; Subjects will ingest the liquid meal containing alpha-lactalbumin and carbohydrates (0.6 g/kg FFM protein + 0.3 g/kg FFM carbohydrates).; Dietary supplement: Whey; commercially available whey protein; Dietary supplement: Casein; commercially available casein protein
Experimental: Dementia; established diagnosis of dementia	Dietary supplement: Alpha-lactalbumin; Subjects will ingest the liquid meal containing alpha-lactalbumin and carbohydrates (0.6 g/kg FFM protein + 0.3 g/kg FFM carbohydrates).; Dietary supplement: Whey; commercially available whey protein; Dietary supplement: Casein; commercially available casein protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net whole-body protein synthesis	Change in whole-body protein synthesis rate after intake of meal	0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole body collagen breakdown rate	Hydroxyproline enrichment in plasma	Postabsorptive state during 3 hours
Citrulline rate of appearance	Plasma enrichment of citrulline	Postabsorptive state during 2 hours
Skeletal and respiratory muscle strength	Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between older adults with and without MCI.	1 day
Cognitive function and mood	Outcome of neuro-psychological tests in healthy older adults with and without MCI in relation to the tryptophan metabolism	Postabsorptive state during 3 hours and change after feeding
Protein digestion after feeding	Ratio enrichment free phenylalanine versus phenylalanine from protein spirulina	0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Arginine turnover rate	Arginine enrichment in plasma	Postabsorptive state during 3 hours
Tryptophan turnover rate	Tryptophan enrichment in plasma in postabsorptive state and after intake of meal	Postabsorptive state during 3 hours and change after feeding
Insulin response to feeding	Acute change from postabsorptive state after intake of meal	During 3 hours after feeding
Fat-free mass	Characteristics of study subjects	Postabsorptive state during 15 min
Myofibrillar protein breakdown rate	3methylhistidine enrichment in plasma	0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Glycine rate of appearance	Glycine enrichment in plasma	Postabsorptive state during 3 hours
Taurine turnover rate	Enrichment of taurine in plasma	Postabsorptive state during 3 hours

Collaborators and Investigators

• Sponsor: Texas A&M University
• Investigators: Principal Investigator: Marielle P Engelen, PhD, Texas A&M University

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): February 1, 2021

Study Registration Dates

• First Submitted: March 6, 2014
• First Submitted That Met QC Criteria: March 7, 2014
• First Posted (Estimate): March 10, 2014

Study Record Updates

• Last Update Posted (Actual): April 11, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Cognitive function; Mood; Mild cognitive impairment; Muscle function; Alpha-lactalbumin; Protein digestion; Tryptophan digestion
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: 2014-0065