Elderly humans have an increased risk of dementia which begins as mild defects in memory called mild cognitive impairment. Glutathione (GSH), a key endogenous antioxidant has been linked to cognition. This exploratory study will investigate mechanisms linked to GSH for cognitive impairment (and improvement) by studying humans with mild cognitive impairment who will be evaluated 12-weeks after receiving either N-acetylcysteine and glycine (GSH precursors), or receiving alanine, and a further 12-weeks after stopping these supplements.
Subjects with MCI will be recruited by written informed consent using forms approved by the Baylor IRB. Subjects will stop nonvitamin supplements for 4wks before screening labs (blood count, HbA1c, glucose, lipid profile, liver profile, blood urea nitrogen, Creatinine, thyroid stimulating hormone, free T4), and for the entire 24wks duration of the study. 60 fasted subjects will have the following measures before and after 12wks of supplementation with cysteine (as N-acetylcysteine) plus glycine vs alanine: (1) Cognitive function using ADCS-PACC (Alzheimer's Disease Co-operative Study-Preclinical Alzheimer's Cognitive Composite which includes Free and Cued Selective Reminding Test, Immediate and Delayed paragraph recall score, Digit-Symbol Substitution Test, Mini mental state examination; (2) Red-cell concentrations of GSH, cysteine, glycine, glutamic acid; plasma malondialdehyde, F2/F3-isoprostanes, sICAM, sVCAM, E-selectin; endothelial function; (3) Mitochondrial glucose oxidation by calorimetry. Measures will be repeated for washout effects 12-wks after stopping supplements.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
60
Dietary Supplement: glycine will be supplemented in the active arm for 12-weeks
Dietary Supplement: NAC will be supplemented in the active arm for 12-weeks
Dietary Supplement: Alanine will be supplemented in the placebo arm for 12-weeks
Baylor College of Medicine
Houston, Texas, United States
Cognition
Measured using ADCS-PACC
Time frame: Change between 0-weeks and 12-weeks
Concentrations of Glutathione
Measured in red cells
Time frame: Change between 0-weeks and 12-weeks
Concentrations of TBARS, F2,F3 isoprostanes
Measured in plasma
Time frame: Change between 0-weeks and 12-weeks
Endothelial function markers sICAM, sVCAM, E-selectin
Measured in plasma
Time frame: Change between 0-weeks and 12-weeks
Endothelial function
Measured using the EndoPAT system
Time frame: Change between 0-weeks and 12-weeks
Mitochondrial fuel oxidation in fasted and fed states
Measured using calorimetry
Time frame: Change between 0-weeks and 12-weeks
Insulin resistance
Measured as HOMA-IR
Time frame: Change between 0-weeks and 12-weeks
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