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October 01, 1996; 47 (4) ARTICLES

Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients

Dose-response study and correlations with plasma levels

E. J. Pappert, C. C. Tangney, C. G. Goetz, Z. D. Ling, J. W. Lipton, G. T. Stebbins, P. M. Carvey
First published October 1, 1996, DOI: https://doi.org/10.1212/WNL.47.4.1037
E. J. Pappert
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C. C. Tangney
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C. G. Goetz
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Z. D. Ling
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J. W. Lipton
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G. T. Stebbins
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P. M. Carvey
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Citation
Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients
Dose-response study and correlations with plasma levels
E. J. Pappert, C. C. Tangney, C. G. Goetz, Z. D. Ling, J. W. Lipton, G. T. Stebbins, P. M. Carvey
Neurology Oct 1996, 47 (4) 1037-1042; DOI: 10.1212/WNL.47.4.1037

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Abstract

Objective: To determine if ventricular cerebrospinal fluid (vCSF) alpha-tocopherol levels in Parkinson's disease (PD) patients can be increased by oral alpha-tocopherol supplementation and whether vCSF levels are linearly related to plasma alpha-tocopherol levels. Background: In spite of its putative neuroprotective properties, alpha-tocopherol has failed to alter PD clinical progression. However, the ability of supplemental alpha-tocopherol to affect brain or vCSF levels has never been assessed in humans nor has a dose-response curve for alpha-tocopherol in vCSF been established. Methods: Five PD patients with Ommaya catheters received oral dl-alpha-tocopherol over 5 months. Each patient ingested alpha-tocopherol daily with monthly dosage increases (400, 800, 1,600, 3,200, 4,000 IU/day). Plasma and vCSF samples were obtained at baseline and at the end of each month. Alpha-tocopherol levels were determined in triplicate by high-pressure liquid chromatography with fluorometric and electrochemical detection. Results: At baseline, endogenous alpha-tocopherol was detected in plasma and vCSF, with a greater than one-hundred-fold difference between the fluid compartments (mean plasma level 18.76 micro Meter/l (SD +/- 4.69) versus mean CSF level 0.114 micro Meter/l (SD +/- 0.084). A clear dose-response curve occurred in plasma, with statistically significant increases over baseline developing even with 400 IU/d. With higher doses, a significant increase continued without evidence of saturation. However, there was no significant increase in vCSF alpha-tocopherol levels at any dose, including the supraclinical (4,000 IU/d). There was no correlation between plasma and vCSF alpha-tocopherol levels. Conclusion: Oral alpha-tocopherol supplementation, even at supraclinical doses, fails to increase vCSF alpha-tocopherol levels. This lack of change may be due to limited passage across the blood-brain barrier or very rapid alpha-tocopherol metabolism. All prior negative studies on efficacy of alpha-tocopherol in PD may need reevaluation in light of these pharmacologic data.

NEUROLOGY 1996;47: 1037-1042

  • Copyright 1996 by Advanstar Communications Inc.
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