Lurie Center for Autism: Glutathione

Glutathione is sometimes discussed as a Complementary and Alternative Medicine (CAM) for individuals with autism spectrum disorders (ASD). Lurie Center clinicians summarize current research on glutathione.

Glutathione is a sulfur-containing molecule composed of three amino acids, or building blocks of proteins: cysteine, glycine, and glutamic acid. It is a naturally-occurring molecule within cells that participates in the liver’s detoxification of many compounds, such as products from cigarette smoke, alcohol, and overdoses of aspirin and acetaminophen (Tylenol). Glutathione is part of a system of enzymes within all cells that reduce oxidative damage, such as that due to radiation, and it is involved in production of fatty acids¹. It also facilitates the development and function of a variety of immune cells². 

Glutathione was first proposed in autism when signs of oxidative stress in the children’s peripheral blood were documented^{3, 4}. Glutathione also “donates” sulfur groups in chemical reactions through its cysteine component, and was suggested for use in autism due to inferred deficiency in sulfur availability⁴.

Glutathione is not well absorbed when taken by mouth, and oral doses do not raise blood or tissue levels of glutathione. The fragile structure of glutathione cannot survive the gastrointestinal tract. When it is broken down, glutathione releases its component amino acids, two of which are excitatory (glutamate and cysteine) in the nervous system.

The body’s cells must generate their own intracellular glutathione for it to be effective over the long term, and glutathione must be in its reduced form to be active within cells. The unreduced form is not metabolically active. Manufacturers do not indicate if their product is reduced. Reduced glutathione is also very expensive compared to the unreduced form.

There are published reports of intravenous glutathione used for protection from adverse reactions from chemotherapy during treatment for cancer⁵, mild symptomatic improvements in Parkinson’s Disease⁶, and some relief of leg pain in patients with cardiovascular disease⁷. All of these studies were done in normally developed adults but none involved children with developmental disorders. There have been no clinical trials of oral or intravenous glutathione supplementation in children with autism that measured core symptoms of autism.

1. Shan XQ, Aw TY, Jones DP. (1990) Glutathione-dependent protection against oxidative injury. Pharmacol Ther 47:61-71.
2. Droge W, Breitkreutz R. (2000) Glutathione and immune function. Proc Nutr Soc 59:595-600.
3. Chauhan A, Chauhan V, Brown WT, Cohen I. (2004) Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferring—the antioxidant proteins. Life Sci 75:2539-2540.
4. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA. (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80:1611-1617.
5. Cascinu S, Catalano V, Cordella L, Labianca R, Giordano P, Baldelli AM, Beretta GD, Ubiali E, Catalano G (2002) Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: A randomized, double-blind, placebo-controlled trial. J Clin Oncol 20:3478-3483.
6. Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D. (2009) Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov Disord  24:979-983.
7. Arosio E, De Marchi S, Zannoni M, Prior M, Lechi A. (2002) Effect of glutathione infusion on leg arterial circulation, cutaneous microcirculation, and pain-free walking distance in patients with peripheral obstructive arterial disease: A randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 77:754-759.