Glutathione in Mild Cognitive Impairment

  • End date
    Dec 31, 2024
  • participants needed
  • sponsor
    Baylor College of Medicine
Updated on 23 August 2023


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.

Condition Mild Cognitive Impairment
Treatment alanine, glycine, N-acetylcysteine (NAC), N- acetylcysteine plus Glycine v Placebo (alanine)
Clinical Study IdentifierNCT03493178
SponsorBaylor College of Medicine
Last Modified on23 August 2023


Yes No Not Sure

Inclusion Criteria

(1) Diagnosis of Mild Cognitive Impairment
Criteria at study entry: (1) hospitalization within past 3 months; (2) known diabetes; (3)
creatinine greater than or equal to 1.5 mg/dL; (4) hemoglobin concentration less than 11
g/dL; (5) known liver disease, or AST/ALT greater than or equal to 2x ULN; (6) history of
stroke, brain tumor, or active heart failure; (7) history of psychiatric disorders; (8)
untreated depression
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