Glutathione and Neurology

As our lifespan increases, we become more susceptible to persistent health issues. Especially those brought on by oxidative stress, like neurodegenerative diseases [2] which insidiously affect our brain and cognition.

A compromised glutathione system in the brain has a strong correlation with oxidative stress and has been shown to be implicated in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, Huntington’s disease and multiple sclerosis [3-5].

It is now possible to determine the concentration of glutathione in living human brains using magnetic resonance spectroscopy (MRS), with multiple MRS studies showing depleted brain glutathione levels in all the major neurodegenerative diseases [6-9].

Strategies to increase neuronal or brain glutathione as a potential treatment have been proposed by many researchers. However, none of the therapeutic candidates have been successful so far [10-12], with the major impediment for most being a failure to cross the blood-brain barrier. As yet, there is no direct evidence to suggest that orally administered Glyteine can reach the human brain [17]. An MRS human clinical study is underway to determine if oral supplementation with Glyteine can increase brain glutathione levels.


  1. BECKMAN, K.B. and B.N. AMES, The Free Radical Theory of Aging Matures. Physiological Reviews, 1998. 78(2): p. 547-581.
  2. Lin, M.T. and M.F. Beal, Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006. 443(7113): p. 787-795.
  3. Dringen, R. and J. Hirrlinger, Glutathione pathways in the brain. Biol Chem, 2003. 384(4): p. 505-16.
  4. Maher, P., The effects of stress and aging on glutathione metabolism. Ageing Research Reviews, 2005. 4(2): p. 288-314.
  5. Currais, A. and P. Maher, Functional Consequences of Age-Dependent Changes in Glutathione Status in the Brain. Antioxidants & Redox Signaling, 2013. 19(8): p. 813-822.
  6. Mueller, S.G., N. Schuff, and M.W. Weiner, Evaluation of treatment effects in Alzheimer’s and other neurodegenerative diseases by MRI and MRS. NMR in Biomedicine, 2006. 19(6): p. 655-668.
  7. Saharan, S. and P.K. Mandal, The Emerging Role of Glutathione in Alzheimer’s Disease. Journal of Alzheimer’s Disease, 2014. 40(3): p. 519-529.
  8. Mandal, P.K., et al., Brain glutathione levels–a novel biomarker for mild cognitive impairment and Alzheimer’s disease. Biol Psychiatry, 2015. 78(10): p. 702-10.
  9. Rae, C.D. and S.R. Williams, Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy. Anal Biochem, 2017. 529: p. 127-143.
  10. Aoyama, K., M. Watabe, and T. Nakaki, Regulation of Neuronal Glutathione Synthesis. Journal of Pharmacological Sciences, 2008. 108(3): p. 227-238.
  11. Aoyama, K. and T. Nakaki, Impaired Glutathione Synthesis in Neurodegeneration. International Journal of Molecular Sciences, 2013. 14(10): p. 21021-21044.
  12. Gu, F., V. Chauhan, and A. Chauhan, Glutathione redox imbalance in brain disorders. Curr Opin Clin Nutr Metab Care, 2015. 18(1): p. 89-95.
  13. Butterfield, D.A., C.B. Pocernich, and J. Drake, Elevated glutathione as a therapeutic strategy in Alzheimer’s disease. Drug Development Research, 2002. 56: p. 428-437.
  14. Liu, H., et al., Glutathione Metabolism during Aging and in Alzheimer Disease. Annals of the New York Academy of Sciences, 2004. 1019(1): p. 346-349.
  15. Viña, J., et al., Molecular bases of the treatment of Alzheimer’s disease with antioxidants: prevention of oxidative stress. Molecular Aspects of Medicine, 2004. 25(1-2): p. 117-123.
  16. Pocernich, C.B. and D.A. Butterfield, Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochimica Et Biophysica Acta-Molecular Basis of Disease, 2012. 1822(5): p. 625-630.
  17. Cao, P., et al., Therapeutic approaches to modulating glutathione levels as a pharmacological strategy in Alzheimer’s disease. Curr Alzheimer Res, 2015. 12(4): p. 298-313.