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.
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
Allocation
NON_RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
59
Subjects will ingest the liquid meal containing alpha-lactalbumin and carbohydrates (0.6 g/kg FFM protein + 0.3 g/kg FFM carbohydrates).
commercially available whey protein
commercially available casein protein
Texas A&M University
College Station, Texas, United States
Net whole-body protein synthesis
Change in whole-body protein synthesis rate after intake of meal
Time frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Citrulline rate of appearance
Plasma enrichment of citrulline
Time frame: 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.
Time frame: 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
Time frame: Postabsorptive state during 3 hours and change after feeding
Protein digestion after feeding
Ratio enrichment free phenylalanine versus phenylalanine from protein spirulina
Time frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Arginine turnover rate
Arginine enrichment in plasma
Time frame: Postabsorptive state during 3 hours
Whole body collagen breakdown rate
Hydroxyproline enrichment in plasma
Time frame: Postabsorptive state during 3 hours
Tryptophan turnover rate
Tryptophan enrichment in plasma in postabsorptive state and after intake of meal
Time frame: Postabsorptive state during 3 hours and change after feeding
Insulin response to feeding
Acute change from postabsorptive state after intake of meal
Time frame: During 3 hours after feeding
Fat-free mass
Characteristics of study subjects
Time frame: Postabsorptive state during 15 min
Myofibrillar protein breakdown rate
3methylhistidine enrichment in plasma
Time frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Glycine rate of appearance
Glycine enrichment in plasma
Time frame: Postabsorptive state during 3 hours
Taurine turnover rate
Enrichment of taurine in plasma
Time frame: Postabsorptive state during 3 hours
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