Know Your Supplements

Antioxidant Supplements Fail to Prevent Dementia in Older Men

Antioxidant Supplements Fail to Prevent Dementia in Older Men

As we age, our brain cells are exposed to increased levels of oxidative stress. This can damage proteins, lipids, and even our DNA. Antioxidant therapies can counter oxidative stress, but could they also help prevent Alzheimer's disease and other dementias?

New findings published in the Journal of the American Medical Association Neurology (JAMA Neurology) suggest not [1].

The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial, which began in 2002, is the largest prevention trial ever conducted for Alzheimer's disease [1]. It was originally part of an even larger randomized clinical trial called Selenium and Vitamin E Cancer Prevention Trial (SELECT), which tested whether two antioxidant supplements—vitamin E and selenium—could prevent prostate cancer in older men. Over 7,500 participants were randomly assigned to receive either vitamin E, selenium, both, or a placebo. SELECT was stopped early in 2009 due to results showing that these supplements did not prevent prostate cancer, and the vitamin E group showed a trend for an increase in the risk of prostate cancer [2].

Everyone was told to stop taking their supplements, but the PREADViSE trial continued with a smaller cohort of 3,786 people who were followed for seven years. The trial looked at whether their previous supplement use was associated with reduced risk of Alzheimer's disease. It found no difference in the incidence of dementia for any of the groups.

The researchers noted that one major reason for the failure of supplements in preventing dementia was that participants already had a lower dementia risk compared to the general population, perhaps because they had higher levels of education [3-4]. Another possible explanation for the failure of this trial may be because what we call "vitamin E" is actually a family of eight different forms of vitamins. Most vitamin E supplements (including those used in the PREADViSE trial) only contain one of those forms, called alpha-tocopherol. Recent research is revealing that other vitamin E members, such as gamma-tocopherol and beta-tocotrienol, may also be important for health [5].

The results from the PREADViSE study were disappointing but similar to findings from other research on antioxidant supplements [6]. However, multiple observational studies have shown that high dietary intake of vitamin E is linked to a 20–25% lower risk of Alzheimer's disease [7-9]. Thus, choosing a healthy diet rich in many forms of vitamin E may offer greater benefit for brain health compared to taking supplements. Vitamin E is rich in leafy green vegetables, sunflower seeds, and almonds. For other ways to improve cognitive health, see the first steps to protect your cognitive vitality and our blog post on promising diets to improve cognitive vitality.

 

  1. Kryscio RJ, Abner EL, Caban-Holt A et al. (2017) Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol.
  2. Lippman SM, Klein EA, Goodman PJ et al. (2009) Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301, 39-51.
  3. Ott A, Breteler MM, van Harskamp F et al. (1995) Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study. BMJ 310, 970-973.
  4. Stern Y, Gurland B, Tatemichi TK et al. (1994) Influence of education and occupation on the incidence of Alzheimer's disease. JAMA 271, 1004-1010.
  5. Mangialasche F, Solomon A, Kareholt I et al. (2013) Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. Exp Gerontol 48, 1428-1435.
  6. Galasko DR, Peskind E, Clark CM et al. (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69, 836-841.
  7. Li FJ, Shen L, Ji HF (2012) Dietary intakes of vitamin E, vitamin C, and beta-carotene and risk of Alzheimer's disease: a meta-analysis. J Alzheimers Dis 31, 253-258.
  8. Xu W, Tan L, Wang HF et al. (2015) Meta-analysis of modifiable risk factors for Alzheimer's disease. J Neurol Neurosurg Psychiatry 86, 1299-1306.
  9. Morris MC, Evans DA, Bienias JL et al. (2002) Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 287, 3230-3237.

Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.

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