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higher levels of AGE receptors were noted in the 1,021 participants with dementia at the beginning of the study 295 Study 5 Study Design: Observational/Correlational Subjects: 764 adults Results: Skin AGE levels were correlated with poorer cognitive performance and the relationship was similar in those with and without diabetes 296 Confidence of Harmfulness: Low* Glutamate Description: An amino acid and excitatory neurotransmitter Potential Mechanism(s): Excitotoxicity triggering neuroinflammation, oxidative stress, protein aggregation, mitochondrial dysfunction, and nerve cell death 297,298 Scientific Evidence: Study 1 Study Design: Two placebo-controlled intervention trials Subjects: Veterans with Gulf War Illness Dose: A challenge dose of glutamate, in the form of monosodium glutamate (MSG), versus placebo after eating a low-glutamate diet for one month Results: Glutamate inconsistently caused return of symptoms, although symptoms, including cognitive impairment, were reduced after the low-glutamate diet 299,300 Study 2 Study Design: RCT Subjects: 159 dementia patients Dose: 900 mg glutamate in the form of MSG three times daily versus placebo Results: Dementia scores improved in those receiving glutamate 301 Study 3 Study Design: Two research reviews Results: No compelling evidence for glutamate sensitivity as a cause of cognitive or other symptoms in otherwise healthy individuals 302,303 Confidence of Harmfulness: Low* RCT = Randomized controlled trial *High = supportive evidence from multiple randomized controlled trials (RCTs) and observational studies

Similar content being viewed by others Log in or create a free account to read this content Gain free access to this article, as well as selected content from this journal and more on nature.com or Abbreviations AML: acute myeloid leukemia AP-1: activator protein-1 ASK1: apoptosis signal-regulating kinase 1 BCNU: N,N -bis(2-chloroethyl)- N -nitrosourea CDNB: 1-chloro-2,4-dinitrobenzene CFU-GM: colony forming unit-granulocyte, monocyte DXR: doxorubicin EA: ethacrynic acid ERK: extracellular signal-regulated kinase 5-FU: 5-fluorouracil GSH: glutathione GST: glutathione S -transferase H 2 O 2 : hydrogen peroxide HEL: Haloenol lactone HFF: human foreskin fibroblast JNK: c-Jun N-terminal kinase MAPK: mitogen-activated protein kinase MAPEG: membrane-associated proteins in eicosanoid and glutathione MDS: myelodysplastic syndrome NCI: National Cancer Institute NTZ: nitazoxanide ROS: reactive oxygen species TLK117: ( -glutamyl- S -(benzyl)cysteinyl- R (-)-phenylglycine) TRAF2: TNF receptor-associated factor 2 UV: ultraviolet References Litwack G, Ketterer B, Arias IM
