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Neurodegeneration: Implications for Integrative Management
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Parkinson’s Disease as Multifactorial Oxidative Neurodegeneration:
Implications for Integrative Management
Paris Kidd
Altern Med Rev 2000;5(6):502-545.
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ABSTRACT
Parkinson’s disease (PD) is the most common movement pathology, severely
afflicting dopaminergic neurons within the substantia nigra (SN) along with
non-dopaminergic, extra-nigral projection bundles that control circuits for
sensory, associative, premotor, and motor pathways. Clinical, experimental,
microanatomic, and biochemical evidence suggests PD involves multifactorial,
oxidative neurodegeneration, and that levodopa therapy adds to the oxidative
burden. The SN is uniquely vulnerable to oxidative damage, having a high
content of oxidizable dopamine, neuromelanin, polyunsaturated fatty acids,
and iron, and relatively low antioxidant complement with high metabolic
rate. Oxidative phosphorylation abnormalities impair energetics in the SN
mitochondria, also intensifying oxygen free radical generation. These
pro-oxidative factors combine within the SN dopaminergic neurons to create
extreme vulnerability to oxidative challenge. Epidemiologic studies and
long-term tracking of victims of MPTP (1-methyl-4-phenyl- 1,2,3,6,-tetrahydropyridine)
poisoning, suggest oxidative stress compounded by exogenous toxins may
trigger the neurodegenerative progression of PD. Rational, integrative
management of PD requires: (1) dietary revision, especially to lower
calories;
(2) rebalancing of essential fatty acid intake away from pro-inflammatory
and toward anti-inflammatory prostaglandins; (3) aggressive repletion of
glutathione and other nutrient antioxidants and cofactors; (4) energy
nutrients acetyl L-carnitine, coenzyme Q10, NADH, and the membrane
phospholipid phosphatidylserine (PS); (5) chelation as necessary for heavy
metals; and (6) liver P450 detoxification support.
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