Diet supplements and gene therapy tried for Parkinson's disease
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7369.851 (Published 19 October 2002) Cite this as: BMJ 2002;325:851All rapid responses
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Levodopa treatments are thought to be the most effective for
Parkinson’s disease but most patients receiving chronic treatment develop
motor complications, specifically motor fluctuations and dyskinesia (1).
Levodopa may be toxic to dopaminergic neurons in vitro depending upon the
study circumstances. In patients the motor complications caused by
levodopa appear to be related to the manner in which the drug is
administered. The complications of levodopa are most likely to be seen
after pulsatile stimulation of dopamine receptors by short-acting
dopaminergic agents. Apparently these complications are not caused by long
-acting dopaminergic agents.
This makes sense if the primary defect in Parkinson’s, and other
neurodegenerative disorders such as Alzheimer’s, is a regional and/or
systemic impairment of the adequacy of mitochondrial oxidative
phosphorylation (2). Pulsatile stimulation by short-acting dopaminergic
agents are likely to achieve, for a limited period, higher levels of
stimulation of dopamine receptors than long-acting dopaminergic agents. If
the deletarious effects of the levodopa is due to a compounding of an
underlying impairment of the adequacy of mitochondrial oxidative
phosphorylation, then the effect is most likely to be seen when
stimulation of dopamine receptors is greatest. It is under these
circumstances that the demand for energy from ATP hydrolysis is most
likely to exceed the capacity for ATP resynthesis.
Of much greater concern than the motor complications of levodopa is
the prospect of it causing other neurodegenerative disorders such as
Alzheimer’s. Coenzyme Q is more rational therapy for a mitochondrial
disorder than levodopa because it would seem less likely to cause
neurodegenerative disorders (3). Other micronutrients, such as vitamins
B12, folic acid, B6, niacin, C, E, iron, and zinc, that also have the
potential to improve mitochondrial function might enhance the therapetic
benefits of coenzyme Q without increasing the risks of complications (4).
1. Agid Y, Olanow CW, Mizuno Y. Levodopa: why the controversy? Lancet
2002;360:575.
2. Fiddian-Green RG. Might statins cause Parkinsons? bmj.com, 18 Oct
2002
3. Misner BD. Coenzyme Q-10 Repletion bmj.com, 18 Oct 2002
4. Ames BN. Micronutrients prevent cancer and delay aging.
Toxicol Lett. 1998 Dec 28;102-103:5-18.
Competing interests: No competing interests
Mitochondria cells depend upon electron carrier activity in order to
convert macro-substances into energy-producing Adenosine Triphosphate.
Abnormalities may occur when these substrates are exposed to pathologic-,
time- (age), or free radical- (excess) conditions. Such conditions may
deplete the fat-soluble mitochondrial ubiquitous Q-10 substance faster
than the food chain may actively replenish it, rationally supports a
preventative concentrated dose adjunct for treating Parkinson's Disease
persons.
Mitochondrial abnormalities can occur in Steinert's myotonic
dystrophy (DM) and deficiency of coenzyme Q-10 may result due to
pathogenic mechanisms associated with abnormal CTG trinucleotide
amplification.[1]. Researchers have reported developing a system that will
detect abnormal patterns of tissue oxygenation in a well-characterized
patient with a deficiency of skeletal muscle coenzyme Q-10 [2].
Administration of coenzyme Q(10) in conjunction with standard medical
therapy has been reported to augment myocardial kinetics, increase cardiac
output, elevate the ischemic threshold, and enhance functional capacity in
patients with congestive heart failure. Coenzyme Q(10) therapy is
associated with significant functional, clinical, and hemodynamic
improvements within the context of an extremely favorable benefit-to-risk
ratio. Coenzyme Q(10) enhances cardiac output by exerting a positive
inotropic effect upon the myocardium as well as mild vasodilatation [3].
Aging as a pleiotropic process involves both genetic and environmental
factors. Recently it has been demonstrated that dietary constituents may
affect senescence. In the present study, adult (3 month-old) mice were fed
diets supplemented with ubiquinone (coenzyme Q(10)), alpha-lipoic acid,
melatonin or alpha-tocopherol for a six-month period to determine if
antioxidants may reverse or inhibit the progression of certain age-
associated changes in cerebral mitochondrial electron transport chain
(ETS) enzyme activities. The control consisted of a group of mice
maintained on a basal diet for the same period. The activity of cytochrome
c oxidase (Complex IV) increased with age but melatonin supplementation
restored the activity to levels of 3 month-old animals. The activity of
succinate dehydrogenase (Complex II) showed no age-related changes.
However, this enzyme complex was elevated, in animals supplemented with
coenzyme Q(10), alpha-lipoic acid and alpha-tocopherol, above
corresponding values obtained with basal diet. NADH-ubiquinone
oxidoreductase (Complex I) and ubiquinol:ferricytochrome-c oxidoreductase
(Complex III) activities remained unchanged [4].
If environmental or genetic factors are potentiated by time resulting
in depleted levels Coenzyme Q-10, consuming a concentrated dose presents a
rationale means for preventating predicted pathology.
References
[1] Siciliano G, Mancuso M, Tedeschi D, Manca ML, Renna MR, Lombardi
V, Rocchi A, Martelli F, Murri L. Coenzyme Q10, exercise lactate and CTG
trinucleotide expansion in myotonic dystrophy. Brain Res Bull. 2001 Oct-
Nov 1;56(3-4):405-10.
[2] Wariar R, Gaffke JN, Haller RG, Bertocci LA., A modular NIRS
system for clinical measurement of impaired skeletal muscle oxygenation. J
Appl Physiol. 2000 Jan;88(1):315-25.
[3] Sacher HL, Sacher ML, Landau SW, Kersten R, Dooley F, Sacher A,
Sacher M, Dietrick K, Ichkhan K., The clinical and hemodynamic effects of
coenzyme Q10 in congestive cardiomyopathy. Am J Ther. 1997 Feb-Mar;4(2-
3):66-72.
[4] Sharman EH, Bondy SC. Effects of age and dietary antioxidants on
cerebral electron transport chain activity. Neurobiol Aging. 2001 Jul-
Aug;22(4):629-34.
Disclosure: The author reports competing interests from the private
sector involved in the formulating supplemental pharmaceutical grade
Coenzyme Q-10 specifically for use by athletes competing in extreme
endurance exercise events.
Competing interests: No competing interests
Cholesterol lowering statins currently being prescribed for patients
with atherosclerosis may reduce mitochondrial coenzyme Q thus potentially
compromising the adequcy of mitochondrial oxidative phosphorylation. An
indequacy of mitochondrial oxidative phosphorylation appears to be the
primary cause of organ dysfunctions and failures, including a wide
spectrum of mood and behavioural disorders, in the critically ill. In
which case statins cann be expected to increase the likelihood of
developing organs dysfunctions and failures in the event of developing an
acute illness. Given this report might statins also be expected to
increase the likelihood of developing Parkinson's and/or even Alzheimer's
(1)? If so it might indeed be advisable for patients taking statins to
take coenzyme Q supplements.
1. Hyams DE, Roylance PJ, Kruger K, Bodd E. Do we kill our cardiac
patients with statin therapy? Coenzyme Q10, what do we know? Tidsskr Nor
Laegeforen. 1994 Feb 20;114(5):590.
Competing interests: No competing interests
Re: Might statins cause Parkinsons?
It is really quite interesting to observe how strategically discrete
the drug industry has chosen to be, as more and more compromising evidence
pops up, challenging the potential health threat of statin drugs.
Statins unquestionably lower cholesterol. However, there are numerous
alternatives to taking this category of drugs, alternatives that do not
cause undesirable side effects.
Most concerning is the fact that the statin manufacturers have neglected
to include in their patient information the very important fact that
statin therapy impairs the liver synthesis of coenzyme Q10, a substance of
vital importance to virtually all bodily functions.
As a journalist and medical writer, I am apalled, though not
surprised, to witness how relevant and critical information gets swept
under the carpet for the sole purpose of maintaining an existing market
and avoiding to "rock the boat".
More power to those who are able to, and willing to, disclose this
ill-mannered conduct and bring to the surface information that is of
benefit to those who really need to know: the patients.
Competing interests: No competing interests