Alternative Medicine Review 2000 (Dec); 5 (6): 502–545 ~ FULL TEXT
Parris M. Kidd, PhD
Introduction
Parkinson's disease (PD) is the most common disease of motor system
degeneration and, after Alzheimer's disease, the second most common neurodegenerative
disease.1 Parkinson's disease takes a heavy toll in mental anguish, lost
productivity, and health care expenditures. PD prominently features dopamine
transmitter insufficiency, and current management is almost exclusively
reliant on dopamine replacement drugs. But, while these drugs are initially
effective in most patients, they do not slow the underlying degeneration
in the area of the brain most affected, the substantia nigra (SN). Their
effectiveness declines over time and their adverse effects become increasingly
more troublesome. Broader options for long-term management are urgently
needed.
Many different lines of evidence have converged to suggest PD is primarily
an oxidative disease, fueled by endogenous susceptibility and driven by
the cumulative contributions of endogenous and exogenous (environmental)
oxidant stressors. In this review the evidence for the various oxidative
contributions to PD is critiqued, from the perspective of developing a
more effective and necessarily more integrative strategy for its medical
management.
Nutrient Deficiencies in Parkinson's Disease
The brain uses the same nutrients that other organs use; therefore,
all nutrient classes can be useful to Parkinson's patients. Many nutrients
have been found deficient in PD, and others are likely to be deficient
at some point during disease progression. [ 66 ]
Certain individual amino acids are precursors to brain neurotransmitters
and significantly ameliorate symptoms when given as dietary supplements.
Tyrosine, phenylalanine, and tryptophan can all be blocked from absorption
by levodopa, thereby becoming deficient. L-tyrosine is a direct precursor
to levodopa, which is then converted to dopa-mine. Deficiency may develop
due to reduced intake from meat, dairy and eggs, or to diminished enzymatic
conversion from phenylalanine. PD patients also may have impaired capacity
to utilize L-tyrosine, [ 67 ] even though it
may be normally absorbed. [ 68 ] In 1989, Lemoine
and collaborators reported L-tyrosine gave better clinical results and
had many fewer side effects than levodopa when tested in a small group
of patients. [ 66 ] L-tyrosine should not be
taken at the same time of day as levodopa, since it competes for absorption.
D-phenylalanine is another amino acid that should not be taken with
levodopa. [ 66 ] The D-form (DPA specifically;
not the L-form) was reported to improve rigidity, walking, speech difficulties,
and psychic depression, but not tremor. [ 69 ]
L-tryptophan also competes with levodopa for absorption. [ 66 ]
Parkinson's disease patients treated with levodopa can manifest low serum
tryptophan, [ 70 ] and L-tryptophan therapy
often helps them break through their depression. [ 71 ]
In a placebo-controlled study, L-tryptophan produced improvements in functional
ability beyond those afforded by levodopa, and also significantly improved
mood and drive. [ 72 ] Given with niacin and
pyridoxine, L-tryptophan was useful in ameliorating the motor complications
from long-term levodopa therapy. [ 66 ]
L-methionine is an essential amino acid, and its supplementation may
benefit PD. In one study, 15 patients who had maximal improvement from
standard medications were increased gradually from 1 g/day to 5 g/day. [ 73 ]
Ten of the 15 improved on all measures except tremor and drooling.
A number of B vitamins may be deficient in PD patients. In one reported
case, deficiency of folic acid due to an inborn error of folate metabolism
generated parkinsonian symptoms which included progressive hypokinesia,
tremor, rigidity, and "pill-rolling," with deficiency of dopamine
though SN degeneration was not found at autopsy. [ 74 ]
Niacin can become deficient in patients treated with levodopa, especially
if it is given with carbidopa or other decarboxylase inhibitors. [ 75 ]
Supplementation with niacin may prolong elevated brain levodopa levels. [ 76 ]
In the case of vitamin B6, treatment with levodopa alone often raises
the levels of this vitamin, so co-supplementation is contraindicated. [ 77 ]
By contrast, treatment with the commonly prescribed levodopa-carbidopa
combination may provoke a marginal B6 deficiency, and supplementation with
B6 can benefit at least some of these patients. [ 78,79 ]
Vitamin B6 can be injected intraspinally with thiamine, for partial symptomatic
relief. [ 66 ]
Vitamin C (ascorbic acid) is sometimes found decreased in Parkinson's
brains. [ 34 ] One double-blind trial in PD
found supplementation produced a modest improvement in functional performance. [ 66 ]
In 1975, Sacks and Simpson reported 4 g/day ascorbic acid lessened nausea
and other levodopa side effects in the case of a 62-year-old man. [ 80 ]
When alternated between ascorbic acid and placebo (citric acid) under double-blind
conditions, his patterns of improvement correlated with the periods of
receiving ascorbic acid.
Vitamin E supplementation may be important for PD patients. A 1988 survey
of the dietary habits of PD patients prior to the age of 40 revealed that
intakes of nuts, oils, and plums relatively high in vitamin E were associated
with lowered risk of PD. [ 66 ] Previous clinical
studies using high doses of encapsulated vitamin E suggested this vitamin
has an important role in slowing disease progression. [ 81,82 ]
Disagreement exists as to whether copper is elevated or deficient in
PD. It was reported elevated in the cerebrospinal fluid of Parkinson's
patients, the degree of elevation being significantly correlated with both
disease severity and rate of progression. [ 83 ]
The researcher suggested copper chelation be used therapeutically in these
cases. However, others reported copper in the SN region was abnormally
low. [ 84,85 ]
Glutathione becomes more depleted from the SN as the disease progresses
(Figure 4). [ 34 ]
N-acetyl cysteine [ 86 ] and alpha-lipoic acid
contribute to GSH repletion and are also potent antioxidants. Building
on the highly positive findings from Italy - that intravenous GSH benefited
all nine patients with early PD46 - the pioneering Perlmutter Center offers
intravenous GSH as the most direct means for GSH repletion. [ 2 ]
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