I have compiled some studies and other references below on glutathione and PD. It seems there is a lot to support the theory of glutathione in its efficacy for alleviating PD symptoms, but it really is hard to get over the results of the most credible study, being the first one on this list below.


Not sure where this exactly leaves things, but for those on the list who have tried glutathione, could you please email me off-list with an indication on how it has affected you, so as to account for the individual non-clinical study responses?.


I will then tally the results and post.


Thanks




Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease.
Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D.
Department of Neurology, University of South Florida, Tampa, Florida 33606, USA. [log in to unmask]

The objective of this study was to evaluate the safety, tolerability, and preliminary efficacy of intravenous glutathione in Parkinson's disease (PD) patients. This was a randomized, placebo-controlled, double-blind, pilot trial in subjects with PD whose motor symptoms were not adequately controlled with their current medication regimen. Subjects were randomly assigned to receive intravenous glutathione 1,400 mg or placebo administered three times a week for 4 weeks. Twenty-one subjects were randomly assigned, 11 to glutathione and 10 to placebo. One subject who was assigned to glutathione withdrew from the study for personal reasons prior to undergoing any postrandomization efficacy assessments. Glutathione was well tolerated and there were no withdrawals because of adverse events in either group. Reported adverse events were similar in the two groups. There were no significant differences in changes in Unified Parkinson's Disease Rating Scale (UPDRS) scores. Over the 4 weeks of study medication administration, UPDRS ADL + motor scores improved by a mean of 2.8 units more in the glutathione group (P = 0.32), and over the subsequent 8 weeks worsened by a mean of 3.5 units more in the glutathione group (P = 0.54). Glutathione was well tolerated and no safety concerns were identified. Preliminary efficacy data suggest the possibility of a mild symptomatic effect, but this remains to be evaluated in a larger study. (c) 2009 Movement Disorder Society.

PMID: 19230029 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/19230029?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=18







Prog Neuropsychopharmacol Biol Psychiatry. 1996 Oct;20(7):1159-70.
Reduced intravenous glutathione in the treatment of early Parkinson's disease
Sechi G, Deledda MG, Bua G, Satta WM, Deiana GA, Pes GM, Rosati G.
Department of Neurology, University of Sassari, Italy.

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/pubmed/8938817







Am J Pathol. 2009 Jul;175(1):54-65. Epub 2009 Jun 4.
Identification of glutathione S-transferase pi as a protein involved in Parkinson disease progression.
Shi M, Bradner J, Bammler TK, Eaton DL, Zhang J, Ye Z, Wilson AM, Montine TJ, Pan C, Zhang J.
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.

Parkinson disease (PD) typically affects the cortical regions during the later stages of disease, with neuronal loss, gliosis, and formation of diffuse cortical Lewy bodies in a significant portion of patients with dementia. To identify novel proteins involved in PD progression, we prepared synaptosomal fractions from the frontal cortices of pathologically verified PD patients at different stages along with age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique. Approximately 100 proteins displayed significant differences in their relative abundances between PD patients at various stages and controls; three of these proteins were validated using independent techniques. One of the confirmed proteins, glutathione S-transferase Pi, was further investigated in cellular models of PD, demonstrating that its level was intimately associated with several critical cellular processes that are directly related to neurodegeneration in PD. These results have, for the first time, suggested that the levels of glutathione S-transferase Pi may play an important role in modulating the progression of PD.

PMID: 19498008 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/19498008?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=6





FASEB J. 2009 Oct;23(10):3263-72. Epub 2009 Jun 19.
Glutathione--a review on its role and significance in Parkinson's disease.
Martin HL, Teismann P.
School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Aberdeen, AB25 2ZD, Scotland, UK.

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting over a million people in the United States alone, and is characterized by rigidity, bradykinesia, resting tremor, and postural instability. Its main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra pars compacta. However, the pathogenesis of this loss is not understood fully. One of the earliest biochemical changes seen in PD is a reduction in the levels of total glutathione, a key cellular antioxidant. Traditionally, it has been thought that this decrease in GSH levels is the consequence of increased oxidative stress, a process heavily implicated in PD pathogenesis. However, emerging evidence suggests that GSH depletion may itself play an active role in PD pathogenesis. This review aims to explore the contribution of GSH depletion to PD pathogenesis.

PMID: 19542204 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19542204?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=4



What’s Hot in Parkinson’s Disease?
July 2009


Glutathione Fails to Demonstrate Significant Improvement in Parkinson’s Disease Symptoms in a Recently Published Trial
Michael S. Okun, M.D.


National Medical Director, National Parkinson Foundation


Dr. Robert Hauser and colleagues at the National Parkinson Foundation (NPF) Center of Excellence at the University of South Florida recently put a highly
controversial drug of interest in Parkinson’s disease to the test. They carefully performed the first randomized double-blind, placebo-controlled clinical trial of intravenous glutathione therapy in twenty one Parkinson’s disease patients. The therapy was well tolerated but there was no significant improvement in any outcome variable.


The National Parkinson Foundation has for many years received a large number of information requests on whether intravenous glutathione therapy works in any positive way for Parkinson’s disease. Glutathione acts as an antioxidant, and has been found to be reduced in the brains of patients with Parkinson’s disease.


Some doctors have chosen to offer a fee for infusion of glutathione service. It is important for patients to be aware of several important facts about glutathione therapy: first, there is a lack of evidence it actually works; second, the therapy requires an intravenous line which has both short and long term risks; and finally, insurance does not cover the costs of this therapy.


There is a clear message for patients and families in the Parkinson’s disease community regarding this drug. At this time there exists no compelling evidence that intravenous glutathione results in any meaningful clinical improvement in Parkinson’s disease patients. Patients should beware of any medical practices offering a fee for glutathione treatment of Parkinson’s disease.


The Hauser article appeared in the journal, Movement Disorders:
Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D. Mov Disord.
Randomized, double-blind, pilot evaluation of intravenous glutathione in
Parkinson's disease. 2009 May 15;24(7):979-83.
*A letter to the editor of Movement Disorders concerning the appropriate
interpretation of the results for patients has been submitted by Dr.’s Jankovic
(Baylor), Lang (Toronto Western), and Okun (University of Florida)


http://www.parkinson.org/Document.Doc?id=497



DRUG INFORMATION ROUNDS
Antioxidants, Supplements, and Parkinson's Disease
Cynthia A Weber, PharmD


Primary Care Resident, Family Medicine, College of Pharmacy, The University of Iowa, Iowa City, IA


Michael E Ernst, PharmD BCPS


Associate Professor (Clinical), Division of Clinical and Administrative Pharmacy, College of Pharmacy; Department of Family Medicine, Roy J and Lucille A Carver College of Medicine, The University of Iowa
Reprints: Dr. Ernst, Department of Family Medicine/01291-A PFP, The University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242-1097, fax 319/384-7822, [log in to unmask]


OBJECTIVE: To review the use of antioxidants and other supplements for the prevention and treatment of Parkinson's disease (PD).


DATA SOURCES: Biomedical literature was accessed through MEDLINE (1996-June 2005); key search terms included Parkinson's disease, coenzyme Q10 (CoQ10), antioxidants, supplements, and glutathione. Pertinent references cited in those articles were also evaluated for inclusion in this review.


DATA SYNTHESIS: Three main antioxidants or supplements have been studied for use in the prevention or treatment of PD: tocopherol, CoQ10, and glutathione. These agents have been studied because of their potential to alter the course of 2 common theories of PD pathogenesis: free radical generation and mitochondrial complex-1 deficiency. The literature search revealed 3 large clinical studies of tocopherol (2 observational, 1 prospective randomized), 4 trials of CoQ10, and 1 study of glutathione. With the exception of the large observational studies with tocopherol and one study of CoQ10 that enrolled 80 patients, each of the other studies retrieved included fewer than 30 patients and were conducted for 3 months or less. Antioxident supplementation, in particular tocopherol, did not appear to alter the course of PD. However, in 2 of the studies of CoQ10 and in the study of glutathione, a small but statistically significant improvement in PD symptoms was observed.


CONCLUSIONS: At present, antioxidants and supplements appear to have a limited role in the prevention or treatment of PD. Of those reviewed here, CoQ10 appears to provide some minor treatment benefits. More study is necessary to determine whether CoQ10 has a significant role as primary or adjunctive therapy in PD.


Key Words: antioxidants, coenzyme Q10, glutathione, Parkinson's disease


Published Online, April 18, 2006. www.theannals.com, DOI 10.1345/aph.1G551 

http://www.theannals.com/cgi/content/abstract/40/5/935





Glutathione peroxidase in early and advanced Parkinson's disease.
A defective antioxidant scavenging system plays a major role in one ofthe theories of the pathogenesis of Parkinson's disease. The aim ofthis study was to investigate whether there is a general difference inantioxidant activity between early and advanced cases of Parkinson'sdisease. Twenty five recently diagnosed patients, without any clinicalfluctuations (group A), and 25 patients in a late phase of the diseasewith severe fluctuations in response to levodopa therapy (group B) wereincluded in the study. Erythrocyte glutathione peroxidase wasdetermined as a measure of antioxidant activity and significantly lowervalues were found in group B than in group A. Regression analyses ingroups A and B showed significant correlation between glutathioneperoxidase and duration of disease, but not between glutathioneperoxidase and age of patients.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1014468/











 
 
 

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