by Zina Kroner, DO
Glutathione has been used to help alleviate some of the symptoms of Parkinson's disease. Glutathione is a small peptide made up of three amino acids – glutamic acid, cysteine and glycine. The active group of this peptide is the sulfhydryl or thiol (SH) group, a bond formed between the amine (NH2) group of cysteine and carboxyl group (COOH) of glutamic acid.
In the human body, glutathione occurs in two forms:
1. the majority of glutathione is present in the reduced form (GSH)
2. and a small percentage of it is present in the oxidized form (GSSG or glutathione disulphide).
The reduced form of glutathione is the active form, and it donates its electrons to highly reactive molecules like free radicals, peroxides and superoxides to stabilize them. The process is called neutralizing the free radicals. During this process, glutathione is oxidized and the harmful free radicals are reduced and neutralized.
The free radicals, peroxides and superoxides are unstable and highly reactive molecules formed as part of normal metabolic processes. These can literally snatch electrons from the surrounding molecules (like DNA, cell membrane and other cell organelles) to stabilize themselves, making the other molecules unstable, that repeats the process, setting off a chain reaction producing more unstable molecules, which can easily result in the collapse of the cell membrane and the membranes of other cell organelles.
Glutathione is synthesized internally in the liver and does not need to be supplied in the diet. A balanced diet has all the necessary precursors for the internal synthesis of glutathione. The ability of glutathione to neutralize these harmful free radicals makes it a major powerful intracellular antioxidant. For glutathione to be active, it needs to be kept in the reduced form in the blood. The oxidized glutathione is immediately recycled back to its reduced form by an enzyme called glutathione reductase, and glutathione is again ready to donate electrons to free radicals. The reduced and oxidized forms of glutathione together are called a redox couple.
Glutathione preserves the integrity and fluidity of the cell membrane. It is available in the cells in relatively high concentrations in the reduced form. Depletion of glutathione levels in the cells leads to excessive formation of reactive oxygen species which puts more stress on the cells. This is called oxidative stress. This increased oxidative stress causes the cell organelles to burn out gradually and lead to eventual cell death. Increased oxidative stress plays a major role in increasing the risk for a variety of cancers, inflammatory and degenerative diseases.
Glutathione and Parkinson’s disease
Glutathione has been extensively studied for its role as an antioxidant in Parkinson’s disease, an adult-onset progressive neurodegenerative disorder. In Parkinson’s disease, there is a selective degeneration of dopaminergic neurons in the substantia nigra of midbrain. Substantia nigra is the part of the brain responsible for physical movement (like walking, moving hands and legs, etc). Hence, degeneration of dopaminergic neurons in substantia nigra causes physical symptoms like tremors, bradykinesia (slow movements), muscle stiffness and loss of automatic movements in Parkinson’s disease.
Progressive degeneration of dopaminergic neurons in substantia nigra is caused by:
1. Excessive formation of reactive oxygen species (ROS)
2. Increased oxidative stress accumulation of abnormal proteins in the cells
3. Drastic depletion of glutathione (GSH) levels
Dopaminergic neurons are more prone to oxidation due to a combination of factors like the metabolism of dopamines, auto-oxidation, increase in iron levels, decrease in glutathione levels and excessive formation of ROS. Oxidative stress needs to be reduced to slow down the progression of symptoms of Parkinson’s disease. Research suggests that oxidative stress can be effectively reduced by increasing the glutathione levels or slowing its degradation in the substantia nigra.
In the body, glutathione is synthesized from 3 amino acids – glutamic acid, cysteine and glycine. The availability of cysteine is the deciding factor (or rate limiting factor) in the synthesis of glutathione.
Dr. Perlmutter’s Research
Dr. David Perlmutter, a board certified neurologist from Naples, Florida, started using intravenous glutathione in 1998 for his Parkinson's patients after he did extensive research on Parkinson’s disease and effects of supplemental glutathione on improving the symptoms of Parkinson’s disease. He is the pioneer in using intravenous glutathione in the treatment of Parkinson’s disease. His research opened new doors in the treatment of Parkinson’s disease and other neurodegenerative diseases. Dr. Perlmutter has successfully used intravenous glutathione in patients with significant improvement in the symptoms. Although glutathione treatment cannot prevent the occurrence of symptoms, it significantly slows down the occurrence of symptoms with improvement in the existing symptoms.
Glutathione supplements do not directly raise the dopamine levels in the brain, instead they improve the efficiency of dopamine in the brain and also increase the sensitivity to dopamine and serotonin.
Glutathione supplements are available in oral, intramuscular, and intravenous forms.
Oral – Glutathione is available in capsule form and also precursors of glutathione are available in powder form to be used as oral supplements. However, recent research suggests that glutathione is digested in the gastrointestinal tract and broken down to its constituents even before it enters the blood. So, oral glutathione supplements are not effective. I prefer to give the natural precursors to glutathione to my patients.
Intramuscular – Glutathione injections are also given intramuscularly. These are mildly effective according to anectodal data.
Intravenous – Glutathione injections given intravenously are the best and most effective form of supplementation. Not only does it reach the brain and potentially improves Parkinson’s symptoms, it also reaches the liver and helps in a variety of functions like neutralization of free radicals via detox pathways. Standard dosage for glutathione supplements is 1400 milligrams mixed with saline, given intravenously for ten minutes three times a week.
Contraindications and Safety:
Glutathione is in the GRAS (generally regarded as safe) category, according to the FDA. However, if you are taking other prescription medicines, glutathione supplements may reduce the efficacy of these medicines. This is because glutathione plays a role in the detoxification function in the liver, removing foreign substances from the body. Prescription medicines may therefore be removed from the system, thus reducing their efficacy
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3.Perlmutter, D. “New Advances in Parkinson’s Disease.” From BrainRecovery.com. Last updated 2004, currently unavailable. Chapter found at www.inutritionals.com/healthy-living/neurodegenerative-conditions/parkinsonsdisease/glutathione/glutathione-8
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