Mild Cognitive ImpairmentNCT02082418
Effects of Alpha-lactalbumin Intake on Metabolic and Cognitive Functions in Elderly
A study testing Alpha-lactalbumin, Whey and Casein in people with Mild Cognitive Impairment, run by Texas A&M University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 55 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- Alpha-lactalbumin, Whey and Casein
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Apr 2014to 1 Dec 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Alpha-lactalbumin, Whey, Casein
- Keywords
- Mild cognitive impairment, Protein digestion, Tryptophan digestion, Cognitive function, Mood, Muscle function, Alpha-lactalbumin
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha-lactalbuminDietary supplement
Subjects will ingest the liquid meal containing alpha-lactalbumin and carbohydrates (0.6 g/kg FFM protein + 0.3 g/kg FFM carbohydrates).
WheyDietary supplement
commercially available whey protein
CaseinDietary supplement
commercially available casein protein
| Study group | Role | What they receive |
|---|---|---|
| Healthy | Experimental | healthy control subjects Receives: Dietary Supplement: Alpha-lactalbumin; Dietary Supplement: Whey; Dietary Supplement: Casein |
| MCI | Experimental | mild cognitive impariments Receives: Dietary Supplement: Alpha-lactalbumin; Dietary Supplement: Whey; Dietary Supplement: Casein |
| Dementia | Experimental | established diagnosis of dementia Receives: Dietary Supplement: Alpha-lactalbumin; Dietary Supplement: Whey; Dietary Supplement: Casein |
What is being measured
The primary outcome is the main question the study is designed to answer.
Net whole-body protein synthesis
Change in whole-body protein synthesis rate after intake of meal
Measured: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Secondary outcomes (12)
Citrulline rate of appearance
Plasma enrichment of citrulline
Measured: 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.
Measured: 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
Measured: Postabsorptive state during 3 hours and change after feeding
Protein digestion after feeding
Ratio enrichment free phenylalanine versus phenylalanine from protein spirulina
Measured: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Arginine turnover rate
Arginine enrichment in plasma
Measured: Postabsorptive state during 3 hours
Whole body collagen breakdown rate
Hydroxyproline enrichment in plasma
Measured: Postabsorptive state during 3 hours
Tryptophan turnover rate
Tryptophan enrichment in plasma in postabsorptive state and after intake of meal
Measured: Postabsorptive state during 3 hours and change after feeding
Insulin response to feeding
Acute change from postabsorptive state after intake of meal
Measured: During 3 hours after feeding
Fat-free mass
Characteristics of study subjects
Measured: Postabsorptive state during 15 min
Myofibrillar protein breakdown rate
3methylhistidine enrichment in plasma
Measured: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Glycine rate of appearance
Glycine enrichment in plasma
Measured: Postabsorptive state during 3 hours
Taurine turnover rate
Enrichment of taurine in plasma
Measured: Postabsorptive state during 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2014 (estimated)
- Study start2 Apr 2014
- Primary completion1 Dec 2016
- Study completion1 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Texas A&M University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marielle PKJ Engelen, PhD, Texas A&M University
- Investigators
- Marielle P Engelen, PhD, Principal investigator, Texas A&M University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02082418
- Sponsor's protocol ID
- 2014-0065
- Status last verified
- Sep 2025
- First submitted
- 6 Mar 2014
- Last updated
- 30 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Huttl VN, Deutz N, Wierzchowska-McNew RA, Ruebush LE, Engelen M. Whole-body and intracellular arginine metabolism in hypertension: role of disease severity and sex. Am J Hypertens. 2026 May 18:hpag047. doi: 10.1093/ajh/hpag047. Online ahead of print.
PubMed 42149813Yu AK, Deutz NEP, Perez CN, DeWandel S, Ruebush LE, Engelen MPKJ. The acute effects of alpha-lactalbumin intake on tryptophan metabolites and mood in older adults with Mild Cognitive Impairment. Nutr Neurosci. 2026 Feb;29(2):180-194. doi: 10.1080/1028415X.2025.2554359. Epub 2025 Sep 14.
PubMed 40946231Kang MC, Deutz NEP, Kirschner SK, Engelen MPKJ. Metabolic kinetics and muscle and brain health markers in older adults, and the role of age and presence of chronic morbidities: A large cross-sectional cohort study. Clin Nutr. 2024 Dec;43(12):36-47. doi: 10.1016/j.clnu.2024.10.015. Epub 2024 Oct 11.
PubMed 39423760Deutz LN, Wierzchowska-McNew RA, Deutz NE, Engelen MP. Reduced plasma glycine concentration in healthy and chronically diseased older adults: a marker of visceral adiposity? Am J Clin Nutr. 2024 Jun;119(6):1455-1464. doi: 10.1016/j.ajcnut.2024.04.008. Epub 2024 Apr 12.
PubMed 38616018
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Alpha-lactalbumin on Metabolic and Cognitive Functions in Healthy Older Adults
- ClinicalTrials.gov ID
- NCT02082418
- Acronym / sponsor ID
- 2014-0065
- Conditions
- Mild Cognitive Impairment
- Keywords
- Mild cognitive impairment, Protein digestion, Tryptophan digestion, Cognitive function, Mood, Muscle function, Alpha-lactalbumin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Texas A&M UniversityUniversity, hospital or other
- Study start
- 2 Apr 2014 (actual)
- Primary completion
- 1 Dec 2016 (actual)
- Study completion
- 1 Dec 2016 (actual)
- First posted
- 10 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy | Experimental | Dietary Supplement: Alpha-lactalbumin, Dietary Supplement: Whey, Dietary Supplement: Caseinhealthy control subjects |
| MCI | Experimental | Dietary Supplement: Alpha-lactalbumin, Dietary Supplement: Whey, Dietary Supplement: Caseinmild cognitive impariments |
| Dementia | Experimental | Dietary Supplement: Alpha-lactalbumin, Dietary Supplement: Whey, Dietary Supplement: Caseinestablished diagnosis of dementia |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alpha-lactalbuminSubjects will ingest the liquid meal containing alpha-lactalbumin and carbohydrates (0.6 g/kg FFM protein + 0.3 g/kg FFM carbohydrates). | Dietary supplement | Dementia, Healthy, MCI |
| Wheycommercially available whey protein | Dietary supplement | Dementia, Healthy, MCI |
| Caseincommercially available casein protein | Dietary supplement | Dementia, Healthy, MCI |
Primary outcome
Net whole-body protein synthesis
Time frame: 0, 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
12 secondary outcomes
Citrulline rate of appearance
Time frame: Postabsorptive state during 2 hours
Skeletal and respiratory muscle strength
Time frame: 1 day
Cognitive function and mood
Time frame: Postabsorptive state during 3 hours and change after feeding
Protein digestion after feeding
Time frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Arginine turnover rate
Time frame: Postabsorptive state during 3 hours
Whole body collagen breakdown rate
Time frame: Postabsorptive state during 3 hours
Tryptophan turnover rate
Time frame: Postabsorptive state during 3 hours and change after feeding
Insulin response to feeding
Time frame: During 3 hours after feeding
Fat-free mass
Time frame: Postabsorptive state during 15 min
Myofibrillar protein breakdown rate
Time frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Glycine rate of appearance
Time frame: Postabsorptive state during 3 hours
Taurine turnover rate
Time frame: Postabsorptive state during 3 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2025.
- Derived from this study: PubMed 42149813Huttl VN, Deutz N, Wierzchowska-McNew RA, Ruebush LE, Engelen M. Whole-body and intracellular arginine metabolism in hypertension: role of disease severity and sex. Am J Hypertens. 2026 May 18:hpag047. doi: 10.1093/ajh/hpag047. Online ahead of print.
- Derived from this study: PubMed 40946231Yu AK, Deutz NEP, Perez CN, DeWandel S, Ruebush LE, Engelen MPKJ. The acute effects of alpha-lactalbumin intake on tryptophan metabolites and mood in older adults with Mild Cognitive Impairment. Nutr Neurosci. 2026 Feb;29(2):180-194. doi: 10.1080/1028415X.2025.2554359. Epub 2025 Sep 14.
- Derived from this study: PubMed 39423760Kang MC, Deutz NEP, Kirschner SK, Engelen MPKJ. Metabolic kinetics and muscle and brain health markers in older adults, and the role of age and presence of chronic morbidities: A large cross-sectional cohort study. Clin Nutr. 2024 Dec;43(12):36-47. doi: 10.1016/j.clnu.2024.10.015. Epub 2024 Oct 11.
- Derived from this study: PubMed 38616018Deutz LN, Wierzchowska-McNew RA, Deutz NE, Engelen MP. Reduced plasma glycine concentration in healthy and chronically diseased older adults: a marker of visceral adiposity? Am J Clin Nutr. 2024 Jun;119(6):1455-1464. doi: 10.1016/j.ajcnut.2024.04.008. Epub 2024 Apr 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marielle P Engelen, PhD principal investigator
Texas A&M University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alpha-lactalbumin, Whey and Casein in people with Mild Cognitive Impairment, run by Texas A&M University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Net whole-body protein synthesis (time frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02082418, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2025.