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Meta-Analysis
. 2012 Nov 14;11(11):CD002854.
doi: 10.1002/14651858.CD002854.pub3.

Vitamin E for Alzheimer's dementia and mild cognitive impairment

Nicolas Farina  1 , Mokhtar Gad El Kareem Nasr Isaac, Annalie R Clark, Jennifer Rusted, Naji Tabet
Affiliations
Meta-Analysis

Vitamin E for Alzheimer's dementia and mild cognitive impairment

Nicolas Farina et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Vitamin E is a dietary compound that functions as an antioxidant scavenging toxic free radicals. Evidence that free radicals may contribute to the pathological processes of cognitive impairment including Alzheimer's disease has led to interest in the use of vitamin E in the treatment of mild cognitive impairment (MCI) and Alzheimer's dementia (AD).

Objectives: To assess the efficacy of vitamin E in the treatment of AD and prevention of progression of MCI to dementia.

Search methods: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources were searched on 25 June 2012 using the terms: "Vitamin E", vitamin-E, alpha-tocopherol.

Selection criteria: All unconfounded, double-blind, randomised trials in which treatment with vitamin E at any dose was compared with placebo for patients with AD and MCI.

Data collection and analysis: Two review authors independently applied the selection criteria and assessed study quality and extracted and analysed the data. For each outcome measure data were sought on every patient randomised. Where such data were not available an analysis of patients who completed treatment was conducted. It was not possible to pool data between studies owing to a lack of comparable outcome measure.

Main results: Only three studies met the inclusion criteria: two in an AD population and one in an MCI population. In the first of the AD studies (Sano 1996) the authors reported some benefit from vitamin E (2000 IU/day) with fewer participants reaching an end point of death, institutionalisation, change to a Clinical Dementia Rating (CDR) of three, or loss of two basic activities of daily living within two years. Of patients completing treatment, 58% (45/77) on vitamin E compared with 74% (58/78) on placebo reached one of the end points (odds ratio (OR) 0.49; 95% confidence interval (CI) 0.25 to 0.96). The second AD treatment study (Lloret 2009) explored the effects of vitamin E (800 IU/day) on cognitive progression in relation to oxidative stress levels. Patients whose oxidative stress markers were lowered by vitamin E showed no significant difference in the percentage change in Mini-Mental State Examination (MMSE) score, between baseline and six months, compared to the placebo group. The primary aim of the MCI study (Petersen 2005) was to investigate the effect of vitamin E (2000 IU/day) on the time to progression from MCI to possible or probable AD. A total of 214 of the 769 participants progressed to dementia, with 212 being classified as having possible or probable AD. There was no significant difference in the probability of progression from MCI to AD between the vitamin E group and the placebo group (hazard ratio 1.02; 95% CI 0.74 to 1.41; P = 0.91).

Authors' conclusions: No convincing evidence that vitamin E is of benefit in the treatment of AD or MCI. Future trials assessing vitamin E treatment in AD should not be restricted to alpha-tocopherol.

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Conflict of interest statement

None known.

Figures

Figure 1
Figure 1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

    1. Lloret A, Badía MC, Mora NJ, Pallardó FV, Alonso MD, Viña J. Vitamin E paradox in Alzheimer's disease: it does not prevent loss of cognition and may even be detrimental. Journal of Alzheimer's Disease 2009;17(1):143‐9. - PubMed
    1. Petersen R, Grundman R, Thomas R, Thal L. Donepezil and vitamin E as treatments for mild cognitive impairment. NeuroBiology of Aging 2004;25(S2):20.
    2. Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al. for the Alzheimer's Disease Cooperative Study Group. Vitamin E and donepezil for the treatment of mild cognitive impairment. The New England Journal of Medicine 2005;352(23):2379‐88. - PubMed
    1. Sano M, Ernesto C, Klauber MR, Schafer K, Woodbury P, Thomas R, et al. and members of the Alzheimer's Disease Cooperative Study. Rationale and design of a multicenter study of selegiline and a‐tocopherol in the treatment of Alzheimer's disease using novel clinical outcomes. Alzheimer Disease and Associated Disorders 1996;10(3):132‐40. - PubMed
    2. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. Effects of selegiline and alpha‐tocopherol on cognitive and functional outcome measures in moderately impaired patients with Alzheimer's disease. Neurology 1997;48(3):A377‐8.
    3. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. for the members of the Alzheimer's Disease Cooperative Study. A controlled trial of selegiline, alpha‐tocopherol, or both as treatment for Alzheimer's disease. New England Journal of Medicine 1997;336(17):1216‐22. - PubMed
    4. Sano M, Ernsto C, Thomas RG, Klauber MR, Klauber MR, Schafer K, et al. A controlled trial of selegiline, alpha tocopherol, or both as treatment for Alzheimer's disease. New England Journal of Medicine 1997;336(9):1216‐7. - PubMed
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References to studies excluded from this review

    1. Alzoubi KH, Khabour OF, Abu Rashid B, Damaj IM, Salah HA. The neuroprotective effect of vitamin E on chronic sleep deprivation‐induced memory impairment: the role of oxidative stress. Behavioural Brain Research 2012;226(1):205‐10. - PubMed
    1. Anand VPR, Kumar BJ, Varghese JM, Das SK. Supplementation of vitamin E improves cognitive status and oxidative stress in type 2 diabetes mellitus. International Research Journal of Pharmacy 2011;2(11):169‐72.
    1. Biesalski HK, Grune T, Tinz J, Zollner I, Blumberg JB. Reexamination of a meta‐analysis of the effect of antioxidant supplementation on mortality and health in randomized trials. Nutrients 2010;2(9):929‐49. - PMC - PubMed
    1. Bittner DM. Combination therapy of acetylcholinesterase inhibitor and vitamin E in Alzheimer disease. Journal of Clinical Psychopharmacology 2009;29(5):511‐3. - PubMed
    1. Brewer GJ. Why vitamin E therapy fails for treatment of Alzheimer's disease. Journal of Alzheimer's Disease 2010;19(1):27‐30. - PMC - PubMed

References to ongoing studies

    1. Gopal V. A pilot study of effect of vitamin E on cognition and measures of activities of daily living in patients with moderately severe Alzheimer's disease. National Research Register2005.
    1. Markesbery W, Schmitt F, Kryscio R. Prevention of Alzheimer's disease by vitamin E and selenium. ClinicalTrials.gov2002.
    1. NCT00056329. Multicenter vitamin E trial in aging persons with Down Syndrome, 2000. clinicaltrials.gov/ct2/show/NCT01594346. (accessed 10 October 2012).
    1. NCT01320527. A clinical trial of a vitamin/nutriceutical formulation for Alzheimer's disease, 2012. clinicaltrials.gov/ct2/show/NCT01320527. (accessed 10 October 2012).

Additional references

    1. Ahlskog JE, Uitti RJ, Low PA, Tyce GM, Nickander KK, Petersen RC, et al. No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease. Movement Disorders 1995;10:566‐73. - PubMed
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition. Washington DC: American Psychiatric Press, 1994.
    1. Behl C, Davis J, Cole GM, Schubert D. Vitamin E protects nerve cells from amyloid‐beta protein toxicity. Biochemical and Biophysical Research Communication 1992;186:944‐50. - PubMed
    1. Berg L. Clinical Dementia Rating (CDR). Psychopharmacology Bulletin 1988;24:637‐9. - PubMed
    1. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews 2010, Issue 2. [DOI: 10.1002/14651858.CD007176] - DOI - PubMed

References to other published versions of this review

    1. Isaac M, Quinn R, Tabet N. Vitamin E for Alzheimer's disease and mild cognitive impairment. Cochrane Database of Systematic Reviews 2000, Issue 4. [DOI: 10.1002/14651858.CD002854] - DOI - PubMed
    1. Isaac MGEKN, Quinn R, Taber N. Vitamin E for Alzheimer’s disease and mild cognitive impairment. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD002854.pub2] - DOI - PubMed

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