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

Mild Cognitive Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02082418
• Other study ID #: 2014-0065
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 2014
• Est. completion date: February 2021

Study information

• Verified date: April 2019
• Source: Texas A&M University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: February 2021
• Est. primary completion date: February 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

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).
• Whey
commercially available whey protein
• Casein
commercially available casein protein

Locations

Country	Name	City	State
United States	Texas A&M University	College Station	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Texas A&M University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Citrulline rate of appearance	Plasma enrichment of citrulline	Postabsorptive state during 2 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	Arginine turnover rate	Arginine enrichment in plasma	Postabsorptive state during 3 hours
Secondary	Whole body collagen breakdown rate	Hydroxyproline enrichment in plasma	Postabsorptive state during 3 hours
Secondary	Tryptophan turnover rate	Tryptophan enrichment in plasma in postabsorptive state and after intake of meal	Postabsorptive state during 3 hours and change after feeding
Secondary	Insulin response to feeding	Acute change from postabsorptive state after intake of meal	During 3 hours after feeding
Secondary	Fat-free mass	Characteristics of study subjects	Postabsorptive state during 15 min
Secondary	Myofibrillar protein breakdown rate	3methylhistidine enrichment in plasma	0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Secondary	Glycine rate of appearance	Glycine enrichment in plasma	Postabsorptive state during 3 hours
Secondary	Taurine turnover rate	Enrichment of taurine in plasma	Postabsorptive state during 3 hours