Glutathione and Parkinson's

04/22/2010

Introduction

Glutathione is a molecule and potent antioxidant found in our cells. Glutathione is produced by our bodies and levels decrease with aging, many diseases and Parkinson’s disease. Glutathione is a potent antioxidant in the brain, and the loss of glutathione is one of the earliest reported changes in Parkinson’s disease (PD). In all of us, the brain, like other tissues, is constantly producing free radicals, negative by-products of metabolism that need to be eliminated in order to maintain optimum health. The role of glutathione is to eliminate these free radicals; in essence, putting out a fire. It is unclear whether the low glutathione content in the PD substantia nigra is due to impaired production, or because the burden of free-radicals is excessive. Regardless, clinicians and researchers are asking the question, “Can we treat Parkinson’s disease by replenishing brain glutathione levels?”

History

The first study was published in 1996 by Italian researchers who administered intravenous (IV) glutathione twice daily to 9 individuals with early, untreated PD. There was a 42% reduction in PD symptoms at the end of the 30-day study, and the therapeutic effect was observed to last for 2-4 months. (Sechi G, et al. 1996) The study has had little impact on PD care because it was small and no placebo was used, but this promising preliminary data has not gone unnoticed.

Since the publication of this study, IV glutathione has gained popularity among complementary and alternative medicine (CAM) providers. Dr. David Perlmutter, a neurologist in Florida and an avid proponent of the therapy, claims that 1400 mg IV glutathione administered 3x/ week is able to reduce PD symptoms. 

In 2009, researchers in Florida conducted a preliminary study to determine whether Dr. Perlmutter’s IV protocol showed benefit compared to placebo. Over the four weeks of the study, individuals receiving IV glutathione had a mild improvement in symptoms, while those receiving the placebo did not. When glutathione was stopped, the individuals receiving glutathione lost the symptomatic improvement, and returned to their baseline level of symptoms. (Hauser RA, et al. 2009) It is important to note that the differences between these two groups were not significant. While the study is small and only provides preliminary data, it is promising non-the-less.

Mechanism of Action

Both of the studies published thus far ask the question, “Does glutathione improve symptoms in PD?” This is a topic of debate in the medical community, because no one has been able to propose a mechanism by which glutathione might offer symptomatic relief.   Continued interest in glutathione  explores this molecules anti-oxidant properties.   The loss of glutathione in the substantia nigra precedes PD symptoms by more than a decade, and occurs prior to the formation of Lewy bodies, considered a PD precursor. Just because low glutathione levels correlate with PD severity, doesn’t mean that the loss of glutathione causes the disease. This is highlighted by the fact that glutathione is decreased in many diseases including cancer, vascular disease and other diseases of aging. We have no idea whether glutathione has the potential to retard disease progression, as the study has not yet been done.

Future Research

More information is needed to determine if glutathione is helpful in Parkinson’s disease. Although studies to date showed no significant difference between placebo treatments in glutathione many questions are still unanswered such as the optimal dose, timing of treatment in relation to disease severity, and duration of treatment. This author has received NIH funding to study glutathione in PD patients, using an intranasal delivery system. Spraying fluid into the nostrils provides a delivery mechanism that is less invasive, less expensive, can be administered at home, with the hopes of more direct access to the brain.   Because of the novelty of the approach, the first step is to ask, “Is intranasal glutathione safe and tolerable in individuals with PD

Availability

Oral GSH is available over the counter at most health food stores. However, since glutathione is made up of amino acid precursors (similar to proteins),it is broken down in the gut prior to absorption and therefore little is available for use. It is for this reason that treatments focus on intravenous or IV (administered directly into the bloodstream through the vein

Intravenous glutathione is readily available in most cities, and most providers are using the dosing schedule recommended by Dr. Perlmutter.   IV administration requires frequent trips to your provider’s office and the treatment takes about 20 minutes.  

The therapy is experimental and therefore not covered by most insurance plans.   The estimated cost for IV glutathione therapy runs between $40-$75/ injection, approximately $7,800 per year. The cost for intranasal glutathione is $30-45 per month, approximately $400 per year.   Glutathione is purchased from compounding pharmacies and requires a prescription from a licensed health care provider.

Safety

Glutathione is the most abundant antioxidant in the human body, numerous studies have demonstrated its safety when given as a supplement (oral or IV), and the FDA classifies glutathione as “Generally Regarded as Safe.” (GRAS)   Reported side effects are few and far between, and typically have more to do with the administration of glutathione than the medicine itself, i.e. bruising at the IV site or nasal irritation from the spray. Recently, a group of physicians reported a case of severe liver injury in a Japanese man with PD who was receiving 1,200 mg intravenous glutathione daily for 5 months.   The patient discontinued use of IV glutathione, and gradually recovered. (Naito Y, et al. 2010)

 Conclusion

Might glutathione be that long-sought ticket to neuroprotection? Will we find a way to measure glutathione levels in the brain a decade before the first signs of disease occur? If so, can we supplement glutathione and stave off the disease? Might we be able to slow or stop disease progression in those already diagnosed with PD? Well controlled clinical research trials are the first step in answering these questions. The next decade holds tremendous promise for this and other therapies targeting protection of neurons. It’s exciting that this small, inexpensive, naturally occurring molecule is paving the way, and that some of this research is happening locally.

Author: By Laurie K Mischley, ND

Comment by Dr. Giroux: Glutathione is a powerful antioxidant that protects our cells from the damaging effects of free radicals or highly reactive oxidative species produced by our cells. There are theoretical reasons to believe that this molecule can protect cells from damage. Research does not yet support the statement that glutathione is neuroprotective in people with Parkinson’s disease. Intravenous glutathione treatments are expensive, often marketed as neuroprotective yet without scientific support. Dr. Mischley and other scientists are researching this molecule and only through their continued diligence will we understand its true effect. Participation in well designed clinical trials is one way to advance our knowledge of this interesting molecule.