Pappert E J, Tangney C C, Goetz C G, Ling Z D, Lipton J W, Stebbins G T, Carvey P M
Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Neurology. 1996 Oct;47(4):1037-42. doi: 10.1212/wnl.47.4.1037.
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.
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.
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.
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 microM/l (SD +/- 4.69) versus mean CSF level 0.114 microM/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.
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.
确定口服补充α-生育酚是否能提高帕金森病（PD）患者脑室脑脊液（vCSF）中的α-生育酚水平，以及vCSF水平是否与血浆α-生育酚水平呈线性相关。
尽管α-生育酚具有潜在的神经保护特性，但它未能改变PD的临床进展。然而，补充α-生育酚对大脑或vCSF水平的影响从未在人体中进行过评估，vCSF中α-生育酚的剂量反应曲线也尚未建立。
五名植入Ommaya导管的PD患者在5个月内口服dl-α-生育酚。每位患者每天摄入α-生育酚，每月剂量增加（400、800、1600、3200、4000 IU/天）。在基线和每个月末采集血浆和vCSF样本。通过高压液相色谱结合荧光和电化学检测对α-生育酚水平进行三次测定。
在基线时，血浆和vCSF中检测到内源性α-生育酚，不同液腔之间存在一百倍以上的差异（血浆平均水平18.76μM/l（标准差±4.69），而脑脊液平均水平为0.114μM/l（标准差±0.084）。血浆中出现了明显的剂量反应曲线；即使每天400 IU，与基线相比也有统计学上的显著增加。随着剂量增加，显著增加持续，没有饱和迹象。然而，在任何剂量下，包括超临床剂量（4000 IU/天），vCSF中α-生育酚水平均无显著增加。血浆和vCSF中α-生育酚水平之间无相关性。
口服补充α-生育酚，即使是超临床剂量，也不能提高vCSF中α-生育酚水平。这种缺乏变化可能是由于穿过血脑屏障的通道有限或α-生育酚代谢非常迅速。鉴于这些药理学数据，所有先前关于α-生育酚在PD中疗效的阴性研究可能都需要重新评估。
