ALPHA-TOCOPHEROL IN THE VENTRICULAR CEREBROSPINAL-FLUID OF PARKINSONS-DISEASE PATIENTS - DOSE-RESPONSE STUDY AND CORRELATIONS WITH PLASMA-LEVELS

Objective: To determine if ventricular cerebrospinal fluid (vCSF) alph a-tocopherol levels in Parkinson's disease (PD) patients can be increa sed by oral alpha-tocopherol supplementation and whether vCSF levels a re 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 supp lemental alpha-tocopherol to affect brain or vCSF levels has never bee n assessed in humans nor has a dose-response curve for alpha-tocophero l in vCSF been established. Methods: Five PD patients with Ommaya cath eters received oral dl-alpha-tocopherol over 5 months. Each patient in gested 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 d etermined in triplicate by high-pressure liquid chromatography with fl uorometric and electrochemical detection. Results: At baseline, endoge nous 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 mu M/l (SD +/- 4.69) versus mean CSF level 0.114 mu M/l (SD +/- 0.084). A clear dose-response curve occurred in plasma, w ith statistically significant increases over baseline developing even with 400 IU/d. With higher doses, a significant increase continued wit hout evidence of saturation. However, there was no significant increas e in vCSF alpha-tocopherol levels at any dose, including the supraclin ical (4,000 IU/d). There was no correlation between plasma and vCSF al pha-tocopherol levels. Conclusion: Oral alpha-tocopherol supplementati on, even at supraclinical doses, fails to increase vCSF alpha-tocopher ol levels. This lack of change may be due to limited passage across th e blood-brain barrier or very rapid alpha-tocopherol metabolism. All p rior negative studies on efficacy of alpha-tocopherol in PD may need r eevaluation in light of these pharmacologic data.