Glutathione & Parkinson’s

Parkinson’s disease is a progressive neurodegenerative disorder that is associated with
the presence of Lewy bodies and the loss of dopaminergic neurons within the substantia nigra.
We now know that oxidative stress is a significant contributor to the pathogenesis of Parkinson’s
disease. Additionally, research suggests that glutathione, a thiol tripeptide that is involved in the
scavenging of reactive oxygen species, may play a crucial role in protecting dopaminergic
neurons from oxidative stress. As a result, glutathione is currently being investigated as a
potential therapeutic agent in the treatment of Parkinson’s disease.

The reduced form of glutathione plays a critical role in the substantia nigra, where it
serves as a mediator of oxidative stress. Research demonstrates lower levels of glutathione in the
substantia nigra of postmortem Parkinson’s disease patients relative to age-matched controls,
while glutathione levels in other parts of the brain remained unchanged.

Glutathione levels in the substantia nigra of patients with other neurodegenerative diseases involving the basal
ganglia, such as Supranuclear Palsy and Multiple System Atrophy, were not altered, suggesting
that lower glutathione levels in the substantia nigra is, in fact, a feature of Parkinson’s disease
and not necessarily of neurodegenerative disorders in general.

Because of glutathione’s ability to protect the brain from oxidative stress-induced
damage and because of the facts that glutathione levels are depleted early in the course of
Parkinson’s and the glutathione levels appear to be inversely related to disease severity,
researchers hypothesized that glutathione may be an efficacious therapy in the treatment of
Parkinson’s disease. While studies regarding glutathione and Parkinson’s are comparatively
limited, we do have some data on the intranasal and intravenous routes of administration.
In a randomized, double-blind, placebo-controlled trial involving intranasal glutathione at
two different dosages (100 mg and 200 mg) and a saline control, each administered three times
per day for three months, all cohorts improved during the intervention period.

This included the placebo group. The 200 mg glutathione group did experience improvements in the total Unified
PD Rating Scale (UPDRS) and UPDRS motor subscore over baseline, but neither treatment
group was superior to placebo. Researchers concluded that larger studies that were longer in
duration were necessary to elucidate whether or not intranasal glutathione is superior to placebo
in the treatment of Parkinson’s disease.

In an open-label, small-scale study where researchers administered 600 mg of
intravenous glutathione twice daily for 30 days to early-stage, treatment-naïve Parkinson’s
patients, all nine of the patients improved during the course of the study with a 42% decline in
disability. These benefits lasted 2-4 months after discontinuation of the infusions.
Another study, a randomized, double-blind, placebo-controlled trial, administered 1400
mg of intravenous glutathione or placebo three times per week for four weeks to 20 individuals
with Parkinson’s disease. At the end of the study, the changes in UPDRS scores weren’t
significant, although the glutathione group did experience improvements in UPDRS ADL and
motor subscores during the duration of the study. The glutathione group then saw a worsening of
those scores in the 8 weeks directly following the study. Researchers noted that although the
study results point to symptomatic effect with the administration of intravenous glutathione,
larger studies are needed to draw more concrete conclusions.

The differences in results between the two available studies on intravenous glutathione in
the treatment of Parkinson’s disease may be attributable to a variety of different factors,
including the fact that one study was open label while the other was a randomized clinical trial
and the differences in the degree of disease progression between participants in the two studies.
The open-label, uncontrolled nature of the first study makes its results less reliable than the first,
while it is also highly likely that the recently-diagnosed, treatment-naïve nature of the individuals
in the first study led to a more exaggerated response to the therapy.

Researchers remarked that limited transport of glutathione across the blood brain barrier
and into the substantia nigra could be a potential explanation for the limited efficacy seen with
the administration of glutathione in a condition like Parkinson’s which we know is associated
with insufficient glutathione levels. Researchers are continually seeking to create forms of
glutathione that would be transported more efficiently into the brain.

Intravenous administration of glutathione was found to be safe. No participants withdrew
from the study because of adverse effects, and reported adverse effects were similar to those
reported in the placebo group.

Reference List
1) Sian J, Dexter DT, Lees AJ, Daniel S, Jenner P, Marsden CD. Glutathione- related
enzymes in brain in Parkinson’s disease. Ann Neurol. 1994;36:356–361.
2) Mischley LK, Lau RC, Shankland EG, Wilbur TK, Padowski JM. Phase IIb Study of
Intranasal Glutathione in Parkinson’s Disease. J Parkinsons Dis. 2017;7(2):289–299.
doi:10.3233/JPD-161040
3) Sechi G, Deledda MG, Bua G, Satta WM, Deiana GA, Pes GM, Rosati G. Reduced
intravenous glutathione in the treatment of early Parkinson’s disease. Prog
Neuropsychopharmacol Biol Psychiatry. 1996;20(7):1159-70.
4) Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D. Randomized, doubleblind, pilot evaluation of intravenous glutathione in Parkinson’s disease. Mov Disord.
2009;24(7):979-83.
5) Smeyne M, Smeyne RJ. Glutathione metabolism and Parkinson’s disease. Free Radic
Biol Med. 2013;62:13–25. doi:10.1016/j.freeradbiomed.2013.05.001