Very Interesting Study showing the value of VitaminE and CoQ 10.  Thanks for
sending it out.  Rob
----- Original Message -----
From: Kathrynne Holden, MS, RD <[log in to unmask]>
To: <[log in to unmask]>
Sent: Monday, May 28, 2001 4:23 PM
Subject: From NPF


> Dear Listfriends,
> The topic of CoQ10 comes up frequently, and I thought you might be
> interested in the following report, posted by Dr. Lieberman, on the NPF
> list:
> ==============================
>
>
> --------------------------------------------------------------------------
------
>
>
> Mitochondrial Function and Coenzyme Q10
> in Parkinson's Disease
> By Cliff Shults, M.D., Professor of Neurosciences, University of
> California, San Diego; Chief, Neurology Services, Veterans Affairs San
> Diego, Healthcare System; and Director, National Parkinson Foundation
> Center of Excellence at University of California, San Diego/Salk
> Institute
>
>
> 3-dimentional reconstruction of
> a mitochondrion in a neuron in the brain
> The study of mitochondrial function in Parkinson's disease (PD) was
> stimulated by Dr. William Langston's discovery of a group of intravenous
> drug users who had acutely developed the tremor; rigidity; and slowness
> typical of Parkinson's disease after using a designer narcotic. Dr.
> Langston and his colleagues determined that the chemical in the designer
> narcotic responsible for the development of Parkinson's disease was
> methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). To be toxic to the
> dopamine-producing nerve cells in the substantia nigra (the brain cells
> that are lost in PD) MPTP must first be converted in the brain to the
> actual toxin, MPP+. The nerve cells in the substantia nigra are
> selectively
> damaged by MPP+ because the MPP+ is actively transported into those
> cells.
> Once inside the dopamine-producing nerve cells, the MPP+ is taken up
> into
> the mitochondrion, which is the part of the cells that makes energy.
> MPP+
> interferes with a certain step in energy production, complex I. Through
> interference with energy production and a resultant increase in the
> production of oxygen free radicals, chemicals which are toxic to cells,
> the
> MPP+ causes damage and death of the dopamine-producing nerve cells.
>
> The observation that MPTP is toxic to nerve cells through interference
> with
> mitochondrial function led to studies of mitochondrial function in the
> brains from patients with PD. Dr. Tony Schapira, working with Drs. Peter
> Jenner and David Marsden in London, found that complex I activity was
> selectively reduced in the substantia nigra of patients with PD. At
> about
> the same time, Dr. Davis Parker, who is now at the University of
> Virginia,
> reported a significant reduction in complex I activity in platelets from
> patients with PD. Platelets are the cells in blood that cause it to
> clot.
> Platelets may seem an unusual tissue in which to study brain function,
> but
> many of the biochemical processes that occur in the brain also occur in
> platelets. For example, platelets have been shown to take up dopamine,
> and
> they contain monoamine oxidase B (the enzyme inhibited by selegiline)
> and
> synuclein (the molecule involved in certain cases of familial PD). The
> reports of Schapira and Parker have been subsequently confirmed by other
> investigators.
>
> Although the studies of Schapira and Parker indicated that mitochondrial
> function is reduced in the brain and platelets from Parkinson's disease
> patients, the possibility remained that the reduction was due to factors
> other than PD. One possible confounding factor was the level of
> debilitation. It was conceivable that debilitation associated with
> advanced
> PD might result in reduction in platelet mitochondrial activity in a
> fashion akin to the anemia caused by chronic disease. A second possible
> confounding factor was drug therapy. In the studies of mitochondrial
> function described above, most patients studied were receiving treatment
> with levodopa. This may be of significance because Dr. Serge Przedborski
> and his colleagues at Columbia University have reported that chronic
> treatment of rats with levodopa caused a reversible reduction of complex
> I
> activity in the substantia nigra.
>
> Dr. Richard Haas and I at the University of California, San Diego,
> reasoned
> that if the reduction in complex I activity found in PD is part of the
> process that results in death of dopamine-producing nerve cells in the
> substantia nigra, then it should be found early in the course of the
> illness. On the other hand, if the impairment in complex I activity is
> due
> to debilitation or medication for PD, then the activity should not be
> reduced in patients with early, untreated disease. To address this
> question, our group carried out two studies. First, we evaluated
> mitochondrial function in platelets from a group of patients with
> Parkinson's disease who had early disease and were not on medication for
> PD, and from two control groups, age/sex-matched controls and spouses.
> The
> spouses acted as controls for the home environment. We studied
> mitochondrial function in platelets from 18 PD subjects, 18
> age/sex-matched
> controls and 13 spouses. We found that the activity of complex I was
> significantly lower in the PD patients than in either age/sex-matched
> controls or spouses.
>
> The first part of this study clearly showed that the reduction in the
> activity of complex I defect found in platelets from patients with PD is
> not due to debilitation or the effect of medication for PD. Our finding
> further suggests that impaired complex I function may be part of, or the
> result of, the processes that cause death of the nigral neurons.
>
> To evaluate the possible effects of medications that are commonly used
> to
> treat PD on mitochondrial function, we evaluated platelet mitochondrial
> function a second time in 11 patients after the patients had received
> carbidopa/ levodopa (Sinemet 25/100, one tablet three times each day)
> for
> one month, and a third time after the patients had received
> carbidopa/levodopa and selegiline (Eldepryl, 5 mg twice each day) for an
> additional month. We found that treatment with carbidopa/levodopa and
> selegiline did not affect mitochondrial function in platelets.
>
> A goal of our research is to develop better treatments for PD
> Mitochondria
> produce energy in useful forms for the cells by transferring electrons
> between molecules. The electron acceptor for complex I in the
> mitochondria
> in humans is a molecule named coenzyme Q10. Coenzyme Q10, also known as
> ubiquinone, also appears to play an important role as an anitoxidant.
> Antioxidants are molecules that are able to eliminate free radicals, the
> molecules mentioned above that can damage cells. Coenzyme Q10's dual
> functions as an integral member of the mitochondrial electron transport
> chain and as an anitioxidant make it potentially important in the
> treatment
> of PD because evidence has accumulated that both mitochondrial
> dysfunction
> and damage to nerve cells in the substantia nigra due to oxidative free
> radicals occur in PD.
>
> To further explore the possible causes of the reduction in mitochondrial
> function in the Parkinson's patients, Dr. Haas, Dr. Flint Beal (formerly
> of
> Massachusetts General Hospital, now the Chair of the Neurology
> Department
> at Cornell/New York Hospital), and I measured the levels of coenzyme Q10
> in
> the platelet mitochondria that have been isolated in our original study.
> We
> found that the level of coenzyme Q10 was significantly lower in the PD
> subjects than in the control subjects, who had been matched for age and
> sex.
>
> Dr. Beal and I next investigated whether oral administration of coenzyme
> Q10 could reduce the damage caused by MPTP in one-year-old mice. As
> mentioned above, MPTP is the compound discovered by Dr. Langston that
> selectively injures the dopamine-producing nerve cells in the substantia
> nigra. Four groups of one-year-old mice received either a standard diet
> or
> a diet supplemented with coenzyme Q10 for five weeks. After four weeks,
> one
> group that had received the standard diet and one group that had the
> coenzyme Q10 supplemented diet were treated with MPTP. The four groups
> continued on their assigned diets for an additional week. We found that
> treatment with coenzyme Q10 did not significantly affect the levels of
> dopamine in the striatum in animals that did not receive MPTP. The
> striatum
> is the area of the brain that the dopamine-producing nerve cells in the
> substantia nigra send fibers to. In animals that received MPTP, animals
> fed
> coenzyme Q10 had significantly greater preservation of dopamine in the
> striatum when compared to animals that received a standard diet without
> coenzyme Q10. We also found that the dopaminergic nerve fibers were
> significantly preserved in animals that received coenzyme Q10. Because
> coenzyme Q10 had not been systematically studied in PD patients, we next
> undertook a pilot study in 15 Parkinson's patients of the effects of one
> month of oral coenzyme Q10 (200 mg + vitamin E 400 I two, three, or four
> times/day; five subjects at each dose). We evaluated adverse events,
> plasma
> levels of coenzyme Q10, signs of PD, and complex I activity in platelet
> mitochondria. Oral coenzyme Q10 caused a significant increase in the
> plasma
> level at each dose studied. Coenzyme Q10 was well tolerated, but two
> subjects at the highest dose had mild changes in the urine at the end of
> the study. These changes did not persist and were of uncertain clinical
> significance. In 12 subjects (four subjects at each dose), the activity
> of
> complex I was determined at both the baseline and final visits. When the
> data from all 12 subjects were analyzed together, there was a trend
> toward
> an increase in the activity of complex I.
>
> The above work stimulated development of a study to evaluate the effects
> of
> coenzyme Q10 in patients with early, untreated PD. Development of the
> study
> was a collaborative effort of Dr. Karl Kieburtz, Dr. David Oakes, Dr.
> Ira
> Shoulson and Sandra Plumb of the University of Rochester, Dr. Jay Nutt
> of
> Oregon Health Sciences University, Dr. Jorge Juncos of Emory University,
> Dr. Beal, Dr. Haas, and myself. The study is supported by the National
> Institute of Neurological Disorders and Stroke (NINDS), which is part of
> the National Institutes of Health (NIH), under a new program to carry
> out
> pilot clinical trials of novel therapies for PD and other neurological
> diseases. Drs. Mike Walker and Gene Oliver of NINDS have played
> instrumental roles in the development of this new program, which
> promises
> to be very useful in bringing promising new treatments for PD into
> clinical
> trials.
>
> The study will be carried out by investigators at 12 medical centers,
> all
> of whom are members of the Parkinson Study Group. The Parkinson Study
> Group
> is a consortium of over 50 of the leading clinical centers in PD in
> North
> America. Persons with early PD, who do not require treatment of their PD
> with levodopa or other medication, will be eligible to participate in
> the
> study. Patients will receive one of three doses of coenzyme Q10 (300,
> 600
> or 1200 mg per day) or placebo, so each subject will have a three in
> four
> chance of receiving coenzyme Q10. Each patient will be followed for up
> to
> 17 months. Our study should indicate whether there is evidence that
> coenzyme Q10 can slow the worsening that PD patients typically
> experience.
>
> This line of research began with the clinical observation that a then
> unidentified chemical (MPTP) could cause a parkinsonian syndrome, then
> progressed through the research efforts of many laboratories, and has
> emerged into a clinical trial of a potentially protective treatment for
> PD.
> The support of the National Parkinson Foundation has been very valuable
> to
> our group and many other groups working in this area.
>
> For further details regarding the study, please contact:
>
> Sandy Plumb
> Clincal Trials Coordination Center
> 1351 Hope Avenue, Suite 220, Rochester, NY 14620
> Phone: 716-275-7311
>
>
>
> --
> Kathrynne Holden, MS, RD
> Author: "Eat well, stay well with Parkinson's disease"
> "Constipation and Parkinson's" --  audiocassette & guidebook
> "Guidelines for Medical Nutrition Therapy for Parkinson's
> disease" & Risk Assessment Tools
> "Risk for malnutrition and bone fracture in Parkinson's
> disease," J Nutr Elderly. V18:3;1999.
> http://www.nutritionucanlivewith.com/
>
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