Parkinson's Disease is one of the most disabling disorders in the world and it significantly shortens the lives of those effected. It is a neurological disorder that is characterized by shaking tremors, weakness, stiffness and rigidity. Mental ability decreases and such simple tasks as walking and starting movement can become impossible. The cause of the degeneration has for many years been a mystery, but researchers have described that the Substantia Nigra section of the brain loses its function. Dopamine, a neurotransmitter that helps connect, or carry signals from one neuron to another, decreases significantly and the process worsens.  

Typically the treatment regimens have tried to help replenish Dopamine and help decrease tremors but, the results are generally mixed.In the Nutritional realm over the past decade or so, researchers were looking further into the disease and tried to understand the biochemical process a bit better. Over time, as with many other degenerative diseases, they were looking at oxidative stress as a contributor to the brain degeneration. With an understanding of free radical pathology and antioxidant benefit, the focus switched to helping to stop oxidative damage. Researchers soon found themselves looking at Glutathione levels in effected tissues and found them to be depleted. Is this a possible cause of the disease? Might this lead to a new line of reasoning and new treatment?

Well, it does seem that Glutathione is extremely important to the brain, and especially the Substantia Nigra. It probably has a lot to do with the disease.More importantly, therapy with Glutathione intravenously has shown some very significant results. In a variety of institutions (as well as in my office), IV treatment has helped to change the course of this disease. Patients that are having difficulty with movement are doing much better, tremors have become far less obvious, and we've noticed improvement in memory and concentration. Weakness, stiffness and balance have improved greatly as well. 

The treatment needs to be done 2 - 3 times a week, and results are usually seen within a week or so. Intravenous access is necessary because it carries with it 100% absorption of product. Oral forms of Glutathione are not absorbed well at all. Results have been seen only with the intravenous technique.The attached articles support this view. 

Looking at diseases with a "nutritional eye" has always yielded new pathways to follow and new, viable techniques of treatment. 

Stay tuned for more surprising info!!

Dr. Chris Calapai

Parkinson's disease: a disorder due to nigral glutathione deficiency?

Amino acid analysis of autopsied human brain showed reduced glutathione (GSH) content significantly lower in the substantia nigra than in other brain regions. GSH was virtually absent in the nigra of patients with Parkinson's disease. Oxidative degradation of L-DOPA and dopamine in vivo may generate reactive oxygen species (hydrogen peroxide, superoxide, hydroxyl radical, or singlet oxygen) which can damage membranes and other cellular components.

Since GSH is an important natural antioxidant, a deficiency of GSH in the substantia nigra could make this region vulnerable to oxidative injury. If confirmed, the hypothesis that loss of nigrostriatal dopaminergic neurons results from a regional GSH deficiency could have important therapeutic implications for the management and prevention of Parkinson's disease. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7162692&dopt=Citation 

Mitochondrial impairment as an early event in the process of apoptosis induced by glutathione depletion in neuronal cells: relevance to Parkinson's disease.

In Parkinson's disease (PD), dopaminergic cell death in the substantia nigra was associated with a profound glutathione (GSH) decrease and a mitochondrial dysfunction. The fall in GSH concentration seemed to appear before the mitochondrial impairment and the cellular death, suggesting that a link may exist between these events. 

The relationships between GSH depletion, reactive oxygen species (ROS) production, mitochondrial dysfunction and the mode of cell death in neuronal cells remain to be resolved and will provide important insights into the etiology of Parkinson's disease. An approach to determine the role of GSH in the mitochondrial function and in neurodegeneration was to create a selective depletion of GSH in a neuronal cell line in culture (NS20Y) by inhibiting its biosynthesis with L-buthionine-(S,R)-sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase. 

This treatment led to a nearly complete GSH depletion after 24 hr and induced cellular death via an apoptotic pathway after 5 days of BSO treatment. By using the reactive oxygen species-sensitive probe 2',7'-dichlorofluorescin, we observed that the rapid GSH depletion was accompanied, early in the process, by a strong and transient intracellular increase in reactive oxygen species evidenced after 1 hr with BSO, culminating after 3 hr when the GSH level decreased to 30% of normal. GSH depletion induced a loss of mitochondrial function after 48 hr of BSO treatment. In particular, the activities of complexes I, II and IV of the respiratory chain were decreased by 32, 70 and 65%, respectively as compared to controls. 

These results showed the crucial role of GSH for maintaining the integrity of mitochondrial function in neuronal cells. Oxidative stress and mitochondrial impairment, preceding DNA fragmentation, could be early events in the apoptotic process induced by GSH depletion. Our data are consistent with the hypothesis that GSH depletion could contribute to neuronal apoptosis in Parkinson's disease through oxidative stress and mitochondrial dysfunction.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9783733&dopt=Citation

Reduced intravenous glutathione in the treatment of early Parkinson's disease.

1. Several studies have demonstrated a deficiency in reduced glutathione (GSH) in the nigra of patients with Parkinson's Disease (PD). In particular, the magnitude of reduction in GSH seems to parallel the severity of the disease. This finding may indicate a means by which the nigra cells could be therapeutically supported.

2. The authors studied the effects of GSH in nine patients with early, untreated PD. GSH was administered intravenous, 600 mg twice daily, for 30 days, in an open label fashion. Then, the drug was discontinued and a follow-up examination carried-out at 1-month interval for 2-4 months. Thereafter, the patients were treated with carbidopa-levodopa. 

3. The clinical disability was assessed by using two different rating scale and the Webster Step-Second Test at baseline and at 1-month interval for 4-6 months. All patients improved significantly after GSH therapy, with a 42% decline in disability. Once GSH was stopped the therapeutic effect lasted for 2-4 months. 

4. Our data indicate that in untreated PD patients GSH has symptomatic efficacy and possibly retards the progression of the disease. 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8938817&dopt=Citation