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Parkinson's Disease: Is Victory in
Sight?
With complete references for researchers
If research into Parkinson's disease continues at its
present pace this dreaded disease may well be fully understood and largely
preventable by the year 2000.
Parkinson's disease (paralysis, shaking palsy) was first described in
1817. L-dopa, the mainstay of current drug therapy was introduced in 1970 and
since then hundreds of research papers have been published on the disease. It
is now increasingly clear not only what causes Parkinson's, but also how it can
be prevented and its relentless progress slowed down.
Incidence and Symptoms
Idiopathic (of no known cause) Parkinson's disease
affects about one percent of the population over the age of 60 years in the
United States. It is more common among men than among women and also seems to
be more widespread in northern countries. The incidence of the disease
increases with age although aging itself is not believed to be a causative
factor. Parkinson's disease is rarely inherited and less than one per cent of
all cases are thought to have a genetic component. At this time there is no
medical cure for the condition, but drugs which alleviate the symptoms and slow
the progress of the disease are available(1-5).
The main symptom of Parkinson's disease is a pronounced tremor affecting the
extremities notably the hands, chin or lips. The tremor is most evident at rest
and disappears with movement. Other characteristic symptoms of Parkinson's
disease are stiffness or slowness of movement, a shuffling walk, stooped
posture, and difficulties in performing simple tasks. Memory impairment and
cognitive dysfunction are rarely encountered in early stage Parkinson's
disease. Depression is, however, a common feature and about 30 per cent of
Parkinson's disease victims eventually develop Alzheimer's disease or other
forms of dementia(1-3,6-8).
Environmental and Dietary Factors
Parkinson-like symptoms can also occur as a result of
head injuries, carbon monoxide poisoning or poisoning by pharmaceutical or
other drugs. Certain diuretics (reserpine), antipsychotics (chlorpromazine),
and heart drugs (verapamil) have all been implicated in causing or worsening
Parkinson's disease symptoms as has the "designer drug" MPTP (methyl phenyl-
tetrahydropyridine). In some cases, drug-induced Parkinson's disease may be
halted or reversed if the drug is promptly withdrawn. Naproxen and other NSAIDs
(non-steroidal anti-inflammatory drugs) may also exacerbate Parkinson's
disease(1,2,8-10).
Recent research carried out in Iceland, which has a very high incidence of
Parkinson's disease, has shown that children born during or after a whooping
cough (pertuses) epidemic are particularly vulnerable to Parkinson's disease
in later life(11). This finding supports the idea that Parkinson's disease may
develop later in life as a result of a neurotoxi event which occurred at an
early age(8).
The main pathological feature of Parkinson's disease is the progressive
destruction of dopamine-producing cells in the substantial
nigra region of the
brain stem. The loss of dopamine production affects the balance between
dopamine and acetylcholine in the brain with the result that messages to the
muscles become garbled. It is estimated that the characteristic Parkinson's
disease symptoms develop once 70 per cent of the dopaminergic neurons in the
substantial
nigra have been destroyed(1,2,5,8).
The question as to what causes the destruction of the dopamine-producing cells
has puzzled researchers for years but a consensus is now emerging that
Parkinson's disease is caused by oxidative stress and metal toxicity(1,2,5,8).
The idea that oxidative stress, ie. an excess of free radicals in the body, can
cause disease was first brought forward in 1983(12). In 1994 Professors
Halliwell and Jenner of King's College, London proposed that neurodegenerative
diseases and Parkinson's disease in particular were the result of oxidative
stress(13,14). Numerous studies have shown that Parkinson's disease victims
have low levels of natural antioxidants (glutathione and super oxide dismutase)
and high levels of iron in the substantial nigra areas of their brains. It is
believed that iron helps catalyze the free radical reactions which destroy the
dopamine- producing cells(2,8,15-21). Other metals, notably manganese, cadmium,
copper, and mercury (from dental amalgams) have also been implicated as
causative factors in the development of Parkinson's disease(2,8,22-27).
People who live in areas where the aluminum content of the drinking water is
high have an excessive risk of developing Parkinson's disease(4,28-32). Recent
research has linked high aluminum levels in drinking water to acid rain which
leaches the aluminum out of the soil and transfers it to the ground
water(4,28,29). Occupational exposure to pesticides and herbicides has also
been linked to a significantly higher risk of developing Parkinson's
disease(33-36).
Diet is another important factor in Parkinson's disease. Researchers at the
University of Magdeburg in Germany recently reported that people with a high
intake of sugar (mono- and disaccharides) increase their risk of developing
Parkinson's disease by a factor of three as compared to people with a more
moderate intake. The same study also showed that diets high in vitamin C and
beta-carotene provide significant protection(37). American researchers have
concluded that a high intake of animal fats is associated with a five-fold
increase in the risk of developing Parkinson's disease(20).
Antioxidants: The Key to Prevention
and Control
Researchers at the University of Hawaii recently reported that people with a
high blood level of the natural antioxidant uric acid have a lower risk of
developing Parkinson's disease than do people with lower levels. Unfortunately,
high levels of uric acid may cause heart disease and gout, and as a matter of
fact, the overall mortality rate in the high uric acid group was about 30 per
cent higher than in the low uric acid group. Nevertheless, the uric acid study
does provide evidence that high levels of antioxidants may help prevent
Parkinson's disease(21,38).
That antioxidants also slow down the progression of existing Parkinson's
disease was demonstrated in 1991 in a pilot study carried out by Dr. Stanley
Fahn of Columbia University. Dr. Fahn found that Parkinson's disease patients
given large doses of oral vitamin C and synthetic vitamin E supplements (3000
mg and 3200 IU daily respectively) delayed the progression of their disease to
the point where they needed l-dopa 2.5 years later than a group of patients who
were not taking supplements(39,40). Later research has shown that synthetic
vitamin E in itself does not retard the progression of Parkinson's
disease(2,41). Thus it is likely that it was vitamin C by itself or its
combination with vitamin E which was the active component in Dr. Fahn's
experiment. This fits with a later finding that vitamin E, a fat- soluble
vitamin, does not readily cross the blood-brain barrier nor does it accumulate
in the cerebrospinal fluid which bathes the brain(5,42). Vitamin C, on the
other hand, while not crossing the blood-brain barrier does enter the
cerebrospinal fluid and can be found there in concentrations proportional to
dietary intake(43-45). Inasmuch as vitamin C is a highly effective antioxidant
and is particularly adept in quenching hydroxyl radicals (the main culprits in
the dopamine-cell destruction), it is becoming increasingly clear that this
vitamin may be an excellent protector against Parkinson's disease and can
materially help in slowing down the progression of the disease(46).
Flavonoids, and in particular the proanthocyanidins (grape seed and pine bark
extracts) which are water-soluble, stronger antioxidants than vitamin C, and
readily cross into the brain fluid should also be excellent candidates as
Parkinson's disease presenters and retarders. Clinical trials are, however,
still required to support this hypothesis(47).
Another promising candidate in Parkinson's disease prevention is coenzyme Q10
(ubiquinone) which also is absorbed in brain fluids and is a very powerful
antioxidant. Recent research has shown that the coenzyme Q10 content of the
mitochondria (energy-producing cell components) in the brain declines rapidly
when Parkinson's disease is induced in monkeys; this reduction in coenzyme Q10
level leads to a detrimental increase in free radical destructive
reactions(48).
The overall conclusion of this recent research is that one can lower one's risk
of developing Parkinson's disease by reducing one's intake of animal fats and
sugar, avoiding excessive exposure to metals such as aluminum, iron, manganese,
mercury, cadmium and copper, and by ensuring an adequate intake of
antioxidants.
Conventional Treatment
Meanwhile, what can be done for people who already have
the disease? Conventional medical treatment relies heavily on l-dopa
(levo-dihydroxy- phenylalanine) a dopamine-precursor which can cross the
blood-brain barrier and is converted to dopamine in the brain. L-dopa is now
rarely used by itself, but rather in combination with carbidopa (Sine met) or
benserazide (Madopar) which protects it from breaking down before it reaches
the brain tissue. As l-dopa must compete with other amino acids in crossing
both from the gut to the blood stream and from the blood stream to the brain it
is usually recommended that it be taken between meals rather than with
meals(1,2,8,49).
Although l-dopa medications can bring significant relief from Parkinson's
disease symptoms they become less effective with time. After four or five years
of increasing dosages their effect becomes sporadic and unpredictable (the
"on-off syndrome") and patients become increasingly helpless and depressed.
There is also evidence that the use of l-dopa medications may lead to a
deficiency of B vitamins, especially niacin and vitamin B-6. Most Parkinson's
disease experts now recommend that l-dopa therapy be started as late as
possible after diagnosis of Parkinson's disease so as to postpone the day when
it no longer works and to limit its many serious adverse effects(1,2,5,7,8,50).
Selegiline (Deprenyl, Eldepryl) is another drug used in Parkinson's disease
therapy. It works by blocking the breakdown of dopamine in the brain. Recent
trials have shown that starting Parkinson's disease patients off on selegiline
can extend the time period before they need l-dopa by about nine
months(2,5,8,51). Combinations of l-dopa medications and selegiline have also
been tried in early stage Parkinson's disease patients, but were found to have
no advantage. As a matter of fact, a recent study concluded that the
combination therapy increased mortality by about 50 per cent when compared to
Parkinson's disease patients treated with l-dopa medications alone(7,52).
Anticholinergenic drugs work by reducing the amount of acetylcholine produced
in the brain and thereby redresses the imbalance between dopamine and
acetylcholine. They are no longer recommended for older patients as they have
serious neuropsychiatry side-effects(7,8).
Alternative Treatment
Until recently there were few alternative treatments
available for Parkinson's disease patients. This is now changing.
Supplementation with vitamin C and E markedly slows the progression of the
disease in its early stages. Other antioxidants such as coenzyme Q10 and
proanthocyanidins may be equally or more effective - however, this remains to
be proven in clinical trials. Supplementation with vitamin B complex may also
be necessary, especially for patients who take l-dopa medications. The timing
of protein intake can markedly increase the effectiveness of l-dopa and thereby
lead to reduced dosage requirements. Researchers now recommend that protein
intake be kept as low as possible and that protein be included primarily in the
evening meal(47,49).
Australian researchers have found that broad beans (Vicia faba) is an extremely
good source of l-dopa and can, in some cases, actually replace l- dopa. A 100 g
serving of broad beans (including the pods) provides about 250 mg of l-dopa and
in addition, a significant amount of proanthocyanidins. The broad beans remain
effective even if canned or frozen, but should always be consumed whole as the
pod has been found to have the highest concentration of l-dopa. Medication
dosage may have to be adjusted if broad beans are consumed on a regular
basis(49,53).
Stress aggravates Parkinson's disease and relaxation therapy has been found
useful in the treatment of the disease. A well thought-out program of rest,
exercise, and physiotherapy can also significantly ameliorate the symptoms of
Parkinson's disease(1,8,54).
The finding that Parkinson's disease is almost certainly caused by oxidative
stress aggravated by metal toxicity is a major step forward in understanding
and eventually conquering the disease. At present the best preventive strategy
is to limit the intake of animal fats and sugar, eat a diet rich in fruits and
vegetables, avoid toxic metals and an excessive iron intake, and insure an
adequate intake of antioxidants. These preventive measures may also be useful
in slowing down the progression of the disease. As research intensifies new
avenues will no doubt open up and by the end of the century Parkinson's disease
will hopefully be both preventable and controllable.
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