Neurochemical Research

, Volume 37, Issue 12, pp 2706–2714 | Cite as

Effect of One-Year Vitamin C- and E-Supplementation on Cerebrospinal Fluid Oxidation Parameters and Clinical Course in Alzheimer’s Disease

  • Sönke Arlt
  • Tomas Müller-Thomsen
  • Ulrike Beisiegel
  • Anatol Kontush
Original Paper


Antioxidant vitamins are being widely discussed as a therapeutic option in Alzheimer’s disease (AD). We recently found that supplementation with vitamin C and E over 1 month leads to an increase of their levels in cerebrospinal fluid (CSF) and a reduction of CSF lipid peroxidation. In the present study, we followed-up the biochemical and clinical effect of vitamin C and E supplementation in an open clinical trial over 1 year. Twelve AD patients stably taking a cholinesterase inhibitor were supplemented with vitamin C (1,000 mg/day) and E (400 I.U./day), while 11 patients taking cholinergic medication only served as a control group. Cognition was assessed at baseline, after 6 months and 12 months using the Mini-Mental State Examination; a more detailed testing of cognitive function was performed at baseline and after 12 months. From eight of the vitamin-supplemented patients, CSF was taken at baseline, after 1 month and after 1 year to measure the antioxidant effect of vitamin supplementation on CSF lipids using a recently established in vitro oxidation assay. CSF antioxidant vitamins were significantly increased after 1 month and 1 year of supplementation, while in vitro oxidation of CSF lipids was significantly reduced only after 1 year of the supplementation. The clinical course of AD did not significantly differ between the vitamin and the control group. We conclude that supplementation with vitamins E and C did not have a significant effect on the course of AD over 1 year despite of a limited antioxidant effect that could be observed in CSF.


Alzheimer’s disease Cerebrospinal fluid Vitamin E, vitamin C Oxidative stress 



We thank Dr. Katrine Semmler for skillfull biochemical measurements and Dr. Stefanie Ganzer-Otte for clinical investigation of some patients. This study was performed in the framework of the Research Group “Molecular Pathomechanisms in Alzheimer’s Disease” and supported by the grant FOR 267/2-1 of the Deutsche Forschungsgemeinschaft.

Conflict of interests

None of the authors report competing interests.


  1. 1.
    Sayre LM, Smith MA, Perry G (2001) Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr Med Chem 8:721–738PubMedCrossRefGoogle Scholar
  2. 2.
    Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G (2000) Oxidative stress in Alzheimer’s disease. Biochim Biophys Acta 1502:139–144PubMedCrossRefGoogle Scholar
  3. 3.
    Atwood CS, Huang X, Moir RD, Tanzi RE, Bush AI (1999) Role of free radicals and metal ions in the pathogenesis of Alzheimer’s disease. Met Ions Biol Syst 36:309–364PubMedGoogle Scholar
  4. 4.
    Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, Floyd RA, Markesbery WR (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA 88:10540–10543PubMedCrossRefGoogle Scholar
  5. 5.
    Schippling S, Kontush A, Arlt S, Buhmann C, Sturenburg HJ, Mann U, Muller-Thomsen T, Beisiegel U (2000) Increased lipoprotein oxidation in Alzheimer’s disease. Free Radic Biol Med 28:351–360PubMedCrossRefGoogle Scholar
  6. 6.
    Bassett CN, Neely MD, Sidell KR, Markesbery WR, Swift LL, Montine TJ (1999) Cerebrospinal fluid lipoproteins are more vulnerable to oxidation in Alzheimer’s disease and are neurotoxic when oxidized ex vivo. Lipids 34:1273–1280PubMedCrossRefGoogle Scholar
  7. 7.
    Arlt S, Beisiegel U, Kontush A (2002) Lipid peroxidation in neurodegeneration: new insights into Alzheimer’s disease. Curr Opin Lipidol 13:289–294PubMedCrossRefGoogle Scholar
  8. 8.
    Lee HP, Zhu X, Casadesus G, Castellani RJ, Nunomura A, Smith MA, Lee HG, Perry G (2010) Antioxidant approaches for the treatment of Alzheimer’s disease. Expert Rev Neurother 10:1201–1208PubMedCrossRefGoogle Scholar
  9. 9.
    Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s disease cooperative study. N Engl J Med 336:1216–1222PubMedCrossRefGoogle Scholar
  10. 10.
    Kontush A, Mann U, Arlt S, Ujeyl A, Luhrs C, Muller-Thomsen T, Beisiegel U (2001) Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer’s disease. Free Radic Biol Med 31:345–354PubMedCrossRefGoogle Scholar
  11. 11.
    Doba T, Burton GW, Ingold KU (1985) Antioxidant and co-antioxidant activity of vitamin C. The effect of vitamin C, either alone or in the presence of vitamin E or a water-soluble vitamin E analogue, upon the peroxidation of aqueous multilamellar phospholipid liposomes. Biochim Biophys Acta 835:298–303PubMedCrossRefGoogle Scholar
  12. 12.
    McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the Nincds-Adrda work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology 34:939–944PubMedCrossRefGoogle Scholar
  13. 13.
    Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRefGoogle Scholar
  14. 14.
    Arlt S, Finckh B, Beisiegel U, Kontush A (2000) Time-course of oxidation of lipids in human cerebrospinal fluid in vitro. Free Radic Res 32:103–114PubMedCrossRefGoogle Scholar
  15. 15.
    Hixson JE, Vernier DT (1990) Restriction Isotyping of human apolipoprotein E by gene amplification and cleavage with Hhai. J Lipid Res 31:545–548PubMedGoogle Scholar
  16. 16.
    Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, Aisen P (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69(7):836–841PubMedCrossRefGoogle Scholar
  17. 17.
    Reddy VP, Zhu X, Perry G, Smith MA (2009) Oxidative stress in diabetes and Alzheimer’s disease. J Alzheimers Dis 16:763–774PubMedGoogle Scholar
  18. 18.
    Brewer GJ (2010) Why vitamin E therapy fails for treatment of Alzheimer’s disease. J Alzheimers Dis 19:27–30PubMedGoogle Scholar
  19. 19.
    Kontush K, Schekatolina S (2004) Vitamin E in neurodegenerative disorders: Alzheimer’s disease. Ann N Y Acad Sci 1031:249–262PubMedCrossRefGoogle Scholar
  20. 20.
    Harrison FE, Allard J, Bixler R, Usoh C, Li L, May JM, McDonald MP (2009) Antioxidants and cognitive training interact to affect oxidative stress and memory in App/Psen1 mice. Nutr Neurosci 12:203–218PubMedCrossRefGoogle Scholar
  21. 21.
    Sung S, Yao Y, Uryu K, Yang H, Lee VM, Trojanowski JQ, Pratico D (2004) Early vitamin E supplementation in young but not aged mice reduces abeta levels and amyloid deposition in a transgenic model of Alzheimer’s disease. FASEB J 18:323–325PubMedGoogle Scholar
  22. 22.
    Murakami K, Murata N, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T (2011) Vitamin C restores behavioral deficits and amyloid-beta oligomerization without affecting plaque formation in a mouse model of Alzheimer’s disease. J Alzheimers Dis 26:7–18PubMedCrossRefGoogle Scholar
  23. 23.
    Saxena G, Singh SP, Agrawal R, Nath C (2008) Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice. Eur J Pharmacol 581:283–289PubMedCrossRefGoogle Scholar
  24. 24.
    Romero A, Egea J, Garcia AG, Lopez MG (2010) Synergistic neuroprotective effect of combined low concentrations of galantamine and melatonin against oxidative stress in Sh-Sy5y neuroblastoma cells. J Pineal Res 49:141–148PubMedGoogle Scholar
  25. 25.
    Melo JB, Sousa C, Garcao P, Oliveira CR, Agostinho P (2009) Galantamine protects against oxidative stress induced by amyloid-beta peptide in cortical neurons. Eur J Neurosci 29:455–464PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Sönke Arlt
    • 1
  • Tomas Müller-Thomsen
    • 1
  • Ulrike Beisiegel
    • 2
  • Anatol Kontush
    • 3
  1. 1.Department of Psychiatry and PsychotherapyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Institute for Biochemistry and Molecular Cell BiologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.Dyslipidemia, Inflammation and Atherosclerosis Research Unit (UMRS 939)National Institute for Health and Medical Research (INSERM)ParisFrance

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