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A surprising number
of enquiries regarding use of glutathione for treatment of PD have been directed
to the editor. We decided to review the videotape and the publication "Powerful
Therapy for Challenging Brain Disorders,"written by David Perlmutter, MD (and
published by the Perlmutter Health Center in Naples, FL). Chapter One deals with
a range of nutritional and vitamin therapies. These include intravenous
glutathione administration, NADH, Coenzyme Q10, phosphatidyl serine, alpha
lipoic acid, vitamin E, Nacetyl-cysteine, acetyl-L-carnitine, vitamin D, vitamin
C and Gingco Biloba. In this article we will focus on Dr.Perlmutter's rationale
for using glutathione, and review the very limited evidence for its
effectiveness in treatment of PD.
Glutathione is
known to be an important antioxidant throughout the body and in the brain.
Glutathione and enzymes related to its metabolism have been reported to be
depleted in the substantia nigra of brains from patients with PD. The primary
role of glutathione is to protect cells from oxyradicals, those destructive
chemicals formed by normal metabolism and by exposure to various environmental
toxicants. Glutathione also enhances the function of other antioxidant compounds
by keeping them in a form suitable for capture of oxyradicals. In 1996, a group
of Italian researchers reported that intravenous glutathione, given twice a day
for one month resulted in a significant improvement of disability. After
glutathione administration was stopped, the therapeutic effect would last for as
long as 2 to 4 months. The study has never been repeated or performed in a way
that would live up to the gold standard of clinical trials, the double-blind,
placebo-controlled trial. Such a test of the effectiveness has never been done,
and it would require that patients with PD be randomly assigned to one of two
treatments, the active intravenous injection glutathione or the intravenous
injection of salt water(saline). The patients would not be allowed to know until
after the study whether they received the glutathione or the saline. Similarly,
the investigating neurologist would not know what the patients received until
after the study. Unfortunately, glutathione is being administered based on
belief that it works rather than on the basis of objective clinical evidence
that it truly works to relieve signs and symptoms and that it slows progression
of disease.
Dr. Perlmutter
began to administer glutathione intravenously (injected directly into the vein)
of PD patients in 1998. He writes, "The effectiveness of this brain antioxidant
in Parkinson's disease is nothing short of miraculous." Whenever a claim of
miraculous treatment is made, patients should have their antennae out and be
especially cautious. Perlmutter also claims, without evidence of a controlled
clinical trial, that "our PD patients are now realizing profound improvements
with respect to reduction of rigidity, increased mobility, improved ability to
speak, less depression and decreased tremor; glutathione has added benefit of
protecting the brain from free radical damage, thus slowing the progression of
the underlying illness."
The "Treatment"
The protocol for
using glutathione is described on Perlmutter's website (www.BrainRecovery.com).
It is a simple matter of purchasing the glutathione dissolved in solution and
having a qualified healthcare practitioner administer it directly into an arm
vein. The solution is infused over a 15-20 min interval of time. The usual dose
is 1400 mg of glutathione three times a week. The injectable form of glutathione
is usually purchased, without a prescription, from a company in Alabama. As
evidence that the treatment works, Dr. Perlmutter relies on his clinical
experience and authority as a board certified neurologist, buttressed by two
testimonial letters from a patient and spouse of a patient who underwent
glutathione therapy. In addition he has videotaped several cases before and
after treatment with glutathione. It appears to be so effective on videotape,
that it is difficult to see why Dr. Perlmutter hasn't studied its effects in a
way that would convince other physicians and patients to use the compound.
Knowledgeable physician's and skeptical patients are aware that videotapes do
not tell the whole truth.
One of the possible
explanations for this lack of research with the compound, according to Dr.
Perlmutter's writing, is that glutathione cannot be patented. Since it cannot be
owned by any particular drug company, he doesn't believe it will ever be tested
as other therapeutic agents are tested.
It is worth
examining excerpts from the two testimonial letters from grateful patients
presented in Dr. Perlmutter's self-published book:
"I received my
first dose of glutathione in your office that day and within two hours I felt
like a new person. I was more animate and expressive almost immediately. Over
the next few weeks, my voice became stronger, I felt less tired and my tremor
almost disappeared. More slowly, my writing has improved; it's not perfect
(never was) but at least with effort and slowing down, I can write legibly now.
I still tend to drool some but even that is much improved."
The other
testimonial letter from a patient's spouse:
"Almost immediately
after your first treatment of glutathione two weeks ago there was a marked
improvement in facial expression, his voice volume and ability to walk and turn.
On our last office visit he received 600 mg and his ability to walk almost
normally lasted the full day and part of the next. He also reports that he has a
general feeling of well-being ... . In addition, we have cut back on his intake
of Sinemet and stopped the Tasmar. In the past without the Sinemet, he had been
unable to walk - his legs practically frozen. With the glutathione therapy, he
can walk with a reduced intake of Sinemet."
Both these letters
attest to the symptomatic relief provided by glutathione. It is surprising that
the anti-oxidant glutathione would alleviate symptoms of PD since its mechanism
of action is to protect the internal environment against oxidative stress. There
is a possibility that glutathione has other poorly understood pharmacological
effects that enhance the action of levodopa or endogenous dopamine. This however
remains to be proven.
It is also possible
that the immediate and short-term benefits of glutathione are the result of a
placebo effect. It is well known that treatments with substances that have no
biological effects can lead to dramatic improvement in signs and symptoms of
disease for many months, and up to a year, if the patient believes he/she is
receiving an active agent. The placebo effect can be very powerful in relieving
symptoms, but is it appropriate to be charged so much in order to be treated
with a placebo?
In summary,
glutathione is an important antioxidant that may or may not eventually be proven
to be useful for the treatment of Parkinson's disease. Dr. Perlmutter and some
of his patients are convinced that intravenous glutathione is a miraculous
treatment for PD. He really claims
two benefits from
the treatment; immediate symptomatic relief and a longer-term neuroprotective
benefit. The immediate symptomatic relief of signs and symptoms should easily be
testable by conducting a double-blind, placebo-controlled trial. To verify that
glutathione slows tile progression
of disease and that
it has neuroprotective effects would require a longer and more expensive
clinical trial. Until intravenous glutathione is subjected to vigorous clinical
trials that include a placebo comparison, patients and physician's will a
convinced of the therapy's effectiveness.
Comment from Dr.
Lieberman
The above is an
accurate assessment of the present status of glutathione.
The University
of Miami has received a grant to study glutathione. The study
Has already
started. The study was obtained with the help of Dr. Perlmutter.