Get Newsletter
AlzRisk Risk Factor Literature Search Strategy and Results

Risk Factor: Nutritional Antioxidants
  (vitamin C, vitamin E)
Risk Factor Type: Nutrition and supplements
Current Understanding:
The tables in the Risk Factor Overview present a modest number of reports with generally null results on nutritional antioxidants (vitamins C and E)—based on dietary intake, dietary supplement use, or plasma levels— and risk of Alzheimer disease (AD) and total dementia. Apart from a possible suggestion of benefits of dietary vitamin E on AD risk, these data provide little support for a role of nutritional antioxidants in the prevention of Alzheimer disease. There are several limitations in these studies that could lead to either spurious negative or positive associations, and thus explain the mixed results. It also remains possible that specific types of exposures defined by timing (e.g., in midlife rather than late life), duration (e.g., over many years), or dietary context (e.g., with phytochemicals) might have beneficial effects that could not be detected in the studies reported to date. The collective findings from current studies do not suggest a protective effect of vitamin C on the risk of developing AD and therefore do not warrant a recommendation of increasing intake of vitamin C in the diet or through supplements to prevent AD. However, individuals might choose to increase intake of vitamin C for other reasons. For vitamin E supplementation, the body of the evidence argues against its use to prevent dementia due to lack of efficacy and potential toxicity. However, dietary vitamin E may be beneficial, and appears to carry little risk of toxicity. For a review of the putative mechanisms by which these nutritional antioxidants may influence AD risk and detailed commentary on interpreting the findings below in a broader context, please view the Discussion.
Last Search Completed: 27 October 2016 - Last content update released on 22 Nov 2016.

Risk Factor Overview


We searched Pubmed for peer-reviewed articles reporting on the association between nutritional antioxidants and Alzheimer’s disease (AD) incidence in cohort or nested case-control studies. The search returned 478 unique citations that, after title and abstract review against our inclusion criteria, were narrowed down to 41 citations for full-text review (all published in English). Of these, 16 fully met criteria for inclusion in our summary tables. We additionally excluded one article that otherwise met our inclusion criteria, but duplicated an analysis from a cohort that contributed data to another included article. We reviewed these duplicate articles on a case-by-case basis, and selected the most informative article based on sample size, follow-up time, exposure assessment or modeling, and appropriateness of analytic methods. Please see our methods section for more detail on our general systematic review methods.

We ran an update of the search in Pubmed covering articles published between April 29, 2013 and October 27, 2016, which returned 141 new citations. We excluded 135 citations that did not meet our inclusion criteria (e.g. topic not appropriate, review or editorial, animal studies). Five studies were excluded after full text review because they did not meet inclusion criteria. One article was added to our Alzrisk tables from this updated search.

Search & Review Flowchart
Search Strategy
Selection of Papers Reporting on Data from the Same Cohort

Search Strategy Flowchart

Search Strategy

Using our systematic review methods, we developed a search strategy (table below) for Pubmed.

Search Strategy Table

Selection of Papers Reporting on Data from the Same Cohort

Some cohort studies produced multiple articles reporting on the association between nutritional antioxidants and risk for Alzheimer’s disease. To avoid presenting duplicate results, we reviewed such articles on a case-by-case basis and selected the most informative article(s) based on sample size, follow-up time, exposure assessment or modeling, and appropriateness of analytic methods.

For each cohort listed below, we cite the duplicative articles we reviewed and give our rationale for their inclusion or exclusion. The full citation for each article is provided in the reference section.

Honolulu-Asia Aging Study (HAAS)

We included main results from Laurin 2002, Laurin 2004, and selected unique results from Masaki 2000. Laurin 2004 reported findings for mid-life (dietary) antioxidant exposure. Both Laurin 2002 and Masaki 2000 reported findings for alternate definitions of (supplemental) antioxidant exposure during late-life (e.g., joint C and E use at one time point vs. multiple time points).

Personnes Agées QUID (PAQUID)

We included Helmer 2003 and excluded Larrieu 2004. The analytic cohorts were identical and Larrieu 2004 only adjusted for age, sex, education, and APOE-4 but Helmer 2003 also adjusted for hypertension, BMI, wine consumption, tobacco use and baseline cognitive status.


Helmer C, Peuchant E, Letenneur L, Bourdel-Marchasson I, Larrieu S, Dartigues JF, Dubourg L, Thomas MJ, Barberger-Gateau P. Association between antioxidant nutritional indicators and the incidence of dementia: results from the PAQUID prospective cohort study. Eur J Clin Nutr. 2003;57(12):1555-61

Larrieu S, Letenneur L, Helmer C, Dartigues JF, Barberger-Gateau P. Nutritional factors and risk of incident dementia in the PAQUID longitudinal cohort. J Nutr Health Aging. 2004;8(3):150-4

Laurin D, Foley DJ, Masaki KH, White LR, Launer LJ. Vitamin E and C supplements and risk of dementia. JAMA. 2002;288(18):2266-8.

Laurin D, Masaki KH, Foley DJ, White LR, Launer LJ. Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. Am J Epidemiol. 2004;159(10):959-67

Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000;54(6):1265-72