Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients : Dose-response study and correlations with plasma levels
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...
Gespeichert in:
| Veröffentlicht in: | Neurology 1996-10, Vol.47 (4), p.1037-1042 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1042 |
|---|---|
| container_issue | 4 |
| container_start_page | 1037 |
| container_title | Neurology |
| container_volume | 47 |
| creator | PAPPERT, E. J TANGNEY, C. C GOETZ, C. G LING, Z. D LIPTON, J. W STEBBINS, G. T CARVEY, P. M |
| description | 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. |
| doi_str_mv | 10.1212/WNL.47.4.1037 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_78420876</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>78420876</sourcerecordid><originalsourceid>FETCH-LOGICAL-c273t-5ee77ef0adb3c5422c17a812d1d604fe148257a4fd2347c55bb00319aaf545f13</originalsourceid><addsrcrecordid>eNo9kT1vFDEQhi0ECkdCSYnkApFqD3_teUMXhfAhnYAiEXSrWXusM_jWG89uovwM_jGOcko10jzPvMW8jL2RYi2VVB9-fd-ujV2btRTaPmMr2apNs9Hq93O2EkJ1je5s95K9IvojRIX27IgddV1rrZEr9u88TTto5uzytMOSE48jn3fIb3GcS3RLgsIdFhxKpimOkHhIS_Q8B_4Tyt84Uh5PiftICIR8gjnWS-If-adM2BSkKY8V0Lz4ew6j5y6Xgql6dc_v4rzjUwLaA094i4lO2IsAifD1YR6z68-XVxdfm-2PL98uzreNU1bPTYtoLQYBftCuNUo5aaGTyku_ESagNJ1qLZjglTbWte0wCKHlGUBoTRukPmbvH3Onkm8WpLnfR3KYEoyYF-ptZ5To7KaKzaPo6guoYOinEvdQ7nsp-ocK-lpBb2xv-ocKqv_2ELwMe_RP9uHnlb87cCAHKRQYXaQnTRlrrDb6P88jka0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>78420876</pqid></control><display><type>article</type><title>Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients : Dose-response study and correlations with plasma levels</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>PAPPERT, E. J ; TANGNEY, C. C ; GOETZ, C. G ; LING, Z. D ; LIPTON, J. W ; STEBBINS, G. T ; CARVEY, P. M</creator><creatorcontrib>PAPPERT, E. J ; TANGNEY, C. C ; GOETZ, C. G ; LING, Z. D ; LIPTON, J. W ; STEBBINS, G. T ; CARVEY, P. M</creatorcontrib><description>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.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/WNL.47.4.1037</identifier><identifier>PMID: 8857741</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Biological and medical sciences ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Medical sciences ; Middle Aged ; Neurology ; Parkinson Disease - drug therapy ; Vitamin E - blood ; Vitamin E - cerebrospinal fluid ; Vitamin E - therapeutic use</subject><ispartof>Neurology, 1996-10, Vol.47 (4), p.1037-1042</ispartof><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c273t-5ee77ef0adb3c5422c17a812d1d604fe148257a4fd2347c55bb00319aaf545f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2474734$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8857741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PAPPERT, E. J</creatorcontrib><creatorcontrib>TANGNEY, C. C</creatorcontrib><creatorcontrib>GOETZ, C. G</creatorcontrib><creatorcontrib>LING, Z. D</creatorcontrib><creatorcontrib>LIPTON, J. W</creatorcontrib><creatorcontrib>STEBBINS, G. T</creatorcontrib><creatorcontrib>CARVEY, P. M</creatorcontrib><title>Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients : Dose-response study and correlations with plasma levels</title><title>Neurology</title><addtitle>Neurology</addtitle><description>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.</description><subject>Biological and medical sciences</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Parkinson Disease - drug therapy</subject><subject>Vitamin E - blood</subject><subject>Vitamin E - cerebrospinal fluid</subject><subject>Vitamin E - therapeutic use</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kT1vFDEQhi0ECkdCSYnkApFqD3_teUMXhfAhnYAiEXSrWXusM_jWG89uovwM_jGOcko10jzPvMW8jL2RYi2VVB9-fd-ujV2btRTaPmMr2apNs9Hq93O2EkJ1je5s95K9IvojRIX27IgddV1rrZEr9u88TTto5uzytMOSE48jn3fIb3GcS3RLgsIdFhxKpimOkHhIS_Q8B_4Tyt84Uh5PiftICIR8gjnWS-If-adM2BSkKY8V0Lz4ew6j5y6Xgql6dc_v4rzjUwLaA094i4lO2IsAifD1YR6z68-XVxdfm-2PL98uzreNU1bPTYtoLQYBftCuNUo5aaGTyku_ESagNJ1qLZjglTbWte0wCKHlGUBoTRukPmbvH3Onkm8WpLnfR3KYEoyYF-ptZ5To7KaKzaPo6guoYOinEvdQ7nsp-ocK-lpBb2xv-ocKqv_2ELwMe_RP9uHnlb87cCAHKRQYXaQnTRlrrDb6P88jka0</recordid><startdate>19961001</startdate><enddate>19961001</enddate><creator>PAPPERT, E. J</creator><creator>TANGNEY, C. C</creator><creator>GOETZ, C. G</creator><creator>LING, Z. D</creator><creator>LIPTON, J. W</creator><creator>STEBBINS, G. T</creator><creator>CARVEY, P. M</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19961001</creationdate><title>Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients : Dose-response study and correlations with plasma levels</title><author>PAPPERT, E. J ; TANGNEY, C. C ; GOETZ, C. G ; LING, Z. D ; LIPTON, J. W ; STEBBINS, G. T ; CARVEY, P. M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c273t-5ee77ef0adb3c5422c17a812d1d604fe148257a4fd2347c55bb00319aaf545f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Biological and medical sciences</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Parkinson Disease - drug therapy</topic><topic>Vitamin E - blood</topic><topic>Vitamin E - cerebrospinal fluid</topic><topic>Vitamin E - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PAPPERT, E. J</creatorcontrib><creatorcontrib>TANGNEY, C. C</creatorcontrib><creatorcontrib>GOETZ, C. G</creatorcontrib><creatorcontrib>LING, Z. D</creatorcontrib><creatorcontrib>LIPTON, J. W</creatorcontrib><creatorcontrib>STEBBINS, G. T</creatorcontrib><creatorcontrib>CARVEY, P. M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PAPPERT, E. J</au><au>TANGNEY, C. C</au><au>GOETZ, C. G</au><au>LING, Z. D</au><au>LIPTON, J. W</au><au>STEBBINS, G. T</au><au>CARVEY, P. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients : Dose-response study and correlations with plasma levels</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>1996-10-01</date><risdate>1996</risdate><volume>47</volume><issue>4</issue><spage>1037</spage><epage>1042</epage><pages>1037-1042</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><coden>NEURAI</coden><abstract>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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>8857741</pmid><doi>10.1212/WNL.47.4.1037</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-3878 |
| ispartof | Neurology, 1996-10, Vol.47 (4), p.1037-1042 |
| issn | 0028-3878 1526-632X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_78420876 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | Biological and medical sciences Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dose-Response Relationship, Drug Female Humans Male Medical sciences Middle Aged Neurology Parkinson Disease - drug therapy Vitamin E - blood Vitamin E - cerebrospinal fluid Vitamin E - therapeutic use |
| title | Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients : Dose-response study and correlations with plasma levels |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T20%3A37%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alpha-tocopherol%20in%20the%20ventricular%20cerebrospinal%20fluid%20of%20Parkinson's%20disease%20patients%20:%20Dose-response%20study%20and%20correlations%20with%20plasma%20levels&rft.jtitle=Neurology&rft.au=PAPPERT,%20E.%20J&rft.date=1996-10-01&rft.volume=47&rft.issue=4&rft.spage=1037&rft.epage=1042&rft.pages=1037-1042&rft.issn=0028-3878&rft.eissn=1526-632X&rft.coden=NEURAI&rft_id=info:doi/10.1212/WNL.47.4.1037&rft_dat=%3Cproquest_cross%3E78420876%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=78420876&rft_id=info:pmid/8857741&rfr_iscdi=true |