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

Not Applicable
Conditions
Mild Cognitive Impairment
Interventions
Dietary Supplement: Alpha-lactalbumin
Dietary Supplement: Whey
Dietary Supplement: Casein
Registration Number
NCT02082418
Lead Sponsor
Texas A&M University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
59
Inclusion Criteria

Not provided

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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
HealthyWheyhealthy control subjects
MCICaseinmild cognitive impariments
MCIWheymild cognitive impariments
HealthyAlpha-lactalbuminhealthy control subjects
HealthyCaseinhealthy control subjects
MCIAlpha-lactalbuminmild cognitive impariments
DementiaWheyestablished diagnosis of dementia
DementiaCaseinestablished diagnosis of dementia
DementiaAlpha-lactalbuminestablished diagnosis of dementia
Primary Outcome Measures
NameTimeMethod
Net whole-body protein synthesis0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal

Change in whole-body protein synthesis rate after intake of meal

Secondary Outcome Measures
NameTimeMethod
Taurine turnover ratePostabsorptive state during 3 hours

Enrichment of taurine in plasma

Citrulline rate of appearancePostabsorptive state during 2 hours

Plasma enrichment of citrulline

Protein digestion after feeding0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal

Ratio enrichment free phenylalanine versus phenylalanine from protein spirulina

Insulin response to feedingDuring 3 hours after feeding

Acute change from postabsorptive state after intake of meal

Arginine turnover ratePostabsorptive state during 3 hours

Arginine enrichment in plasma

Glycine rate of appearancePostabsorptive state during 3 hours

Glycine enrichment in plasma

Tryptophan turnover ratePostabsorptive state during 3 hours and change after feeding

Tryptophan enrichment in plasma in postabsorptive state and after intake of meal

Myofibrillar protein breakdown rate0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal

3methylhistidine enrichment in plasma

Skeletal and respiratory muscle strength1 day

Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between older adults with and without MCI.

Cognitive function and moodPostabsorptive state during 3 hours and change after feeding

Outcome of neuro-psychological tests in healthy older adults with and without MCI in relation to the tryptophan metabolism

Whole body collagen breakdown ratePostabsorptive state during 3 hours

Hydroxyproline enrichment in plasma

Fat-free massPostabsorptive state during 15 min

Characteristics of study subjects

Trial Locations

Locations (1)

Texas A&M University

🇺🇸

College Station, Texas, United States

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