PT  - JOURNAL ARTICLE
AU  - Pappert, E. J.
AU  - Tangney, C. C.
AU  - Goetz, C. G.
AU  - Ling, Z. D.
AU  - Lipton, J. W.
AU  - Stebbins, G. T.
AU  - Carvey, P. M.
TI  - Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients
AID  - 10.1212/WNL.47.4.1037
DP  - 1996 Oct 01
TA  - Neurology
PG  - 1037--1042
VI  - 47
IP  - 4
4099  - http://n.neurology.org/content/47/4/1037.short
4100  - http://n.neurology.org/content/47/4/1037.full
SO  - Neurology1996 Oct 01; 47
AB  - 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