Vitamin E is a potent antioxidant that scavenges free radicals and has sparked interest in the past as a potential option for Alzheimer’s patients.

The term “vitamin E” describes a group of eight fat-soluble compounds, naturally present in food such as vegetable oils, grains, green vegetables, nuts and seeds. The group is composed of four tocopherols and four tocotrienols, each of with has an alfa, beta, gamma e omega isoform. All eight compounds are present and differentially distributed within food sources. Alfa – tocopherol is the primary isoform normally found within vitamin E supplements.

The antioxidant role of vitamin E is based on its chemical structure. They have a chemically functional group (hydroxyl group) in their ring structure (chromanol ring), which can release a hydrogen atom and, in this way, neutralize a variety of aggressive free radicals, including reactive oxygen compounds. This effect is differently pronounced in the various vitamin E compounds: the tocotrienols have a significantly higher antioxidant capacity than alpha-tocopherol, but they are absorbed more inefficiently in the organism[1].

Besides its great antioxidant capability, vitamin E has other neuroprotective functions including anti-inflammatory property, regulation of immune system, reduction of cholesterol levels and influence in gene expression.

The antioxidant activity has been proved in several studies both in vitro and in vivo. One of the most important pieces of evidence was reported on 1997 by Ham and Liebler who gave supplementary vitamin E diet to rats and observed a reduction in the metabolic changes in vitamin E-treated rats[2]. The use of vitamin E in Alzheimer animal models has also showed to reduce symptoms progression and beta amyloid plaques formation [3].

What about the use of vitamin E in humans either to prevent or to reduce cognitive decline in humans?

In 1997 the guideline of the American Psychiatric Association for the treatment of dementias [4] recommended considering vitamin E to slow cognitive decline. But in the 2007 updated guideline, vitamin E was not recommended anymore, because of limited evidence supporting this idea and also because of safety concerns. The concerns about safety arose primarily from one meta-analysis published in 2005 in the journal Annals of Internal Medicine [5] showing that vitamin E supplements were associated with higher all-cause mortality. This meta-analysis was not aimed to Alzheimer’s disease: most of the studies evaluated patients with chronic diseases, and did not consider cognitive deficit or any other symptoms of dementia. However, it created quite a stir in medical societies and generated a bad name for the use of vitamin E supplements.

Since then, several studies have been carried out in both Alzheimer’s and Mild Cognitive Impairment patients, but the evidence remained insufficient for the recommendation of vitamin E supplements[6].

In 2014, a clinical trial of patients with mild or moderate Alzheimer’s disease compared use of memantine (a conventional drug used to treat AD), alpha-tocopherol (2,000 I.U./d), both, or placebo [7]. Compared to placebo, this form of vitamin E was associated with slower functional decline and decreased caregiver burden over an average of 2.27 years. The vitamin E and memantine combination did not maintain this effect. There was no difference in all-cause mortality between groups. With these data, published in the JAMA, vitamin E was “absolved” and returned to the list of therapeutic possibilities for the treatment and prevention of Alzheimer’s disease. Although new studies to prove its effectiveness have yet to be conducted, its use has not shown any major side effects or increased mortality. Thus, the concerns that had previously arisen had disappeared.

It is important to note that the studies cited above as well as many others that have evaluated the role of vitamin E in Alzheimer’s disease, have used supplements containing only alpha tocopherol. This fact is well highlighted in the latest Cochrene-review in 2017 [8], where the authors conclude: “We found no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with Alzheimer’s disease”. In other words, this does not mean that increasing the supply of vitamin E in the diet or using supplements containing other forms of vitamin E (tocopherols and tocotrienols) cannot have such effects – studies with this particular type of supplement have not yet been conducted.

The creator of the Mind diet, Dr. Martha Clare Morris, has also emphasized that the use of vitamin E-rich foods improve cognitive performance in dementia patients and their consumption should be encouraged. In her studies, she found that the highest the amount of vitamin E from food sources, the slowest the cognitive decline in people over 65 years.

This may be a reason for conflicting results in different studies: only alpha-tocopherol, just one of the many naturally occurring vitamin E compounds, has been used in most studies in using supplements.

Our recommendation:

If you want to get all the benefits of vitamin E in preventing neurodegeneration and delaying cognitive deficits, you should increase your consumption of foods rich in natural vitamin E, that is, containing a mixture of tocopherols and tocotrienols. These include dark green vegetables, avocados, sunflower and sesame seeds, red unrefined palm oil, almonds, pumpkin, peanuts and peanut paste, and wheat germ. If you use a supplement, make sure it contains different types of vitamin E compounds, not just alpha-tocopherol, so you can get the best results!

References:

  1. ↑ Lester Packer, Stefan U. Weber, Gerald Rimbach: Molecular Aspects of α-Tocotrienol Antioxidant Action and Cell Signalling. In: The Journal of Nutrition. Band 131, Nr. 2, Februar 2001, S. 369S, doi:10.1093/jn/131.2.369s
  2. ↑Ham AJ, Liebler DC. Antioxidant reactions of vitamin E in the perfused rat liver: product distribution and effect of dietary vitamin E supplementation. Arch Biochem Biophys. 1997 Mar 1;339(1):157-64. doi: 10.1006/abbi.1996.9856. PMID: 9056245.
  3. ↑ Gugliandolo A, Bramanti P, Mazzon E. Role of Vitamin E in the Treatment of Alzheimer’s Disease: Evidence from Animal Models. Int J Mol Sci. 2017;18(12):2504. Published 2017 Nov 23. doi:10.3390/ijms18122504
  4. ↑ Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias of late life. American Psychiatric Association. Am J Psychiatry. 1997 May;154(5 Suppl):1-39. doi: 10.1176/ajp.154.5.1. Erratum in: Am J Psychiatry 1997 Aug;154(8):1180. PMID: 9140238.
  5. ↑ Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. doi: 10.7326/0003-4819-142-1-200501040-00110. Epub 2004 Nov 10. PMID: 15537682.
  6. ↑ Farina N, Isaac MG, Clark AR, Rusted J, Tabet N. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD002854. doi: 10.1002/14651858.CD002854.pub3. Update in: Cochrane Database Syst Rev. 2017 Jan 27;1:CD002854. PMID: 23152215; PMCID: PMC6464798.
  7. ↑ Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial [published correction appears in JAMA. 2014 Mar 19;311(11):1161]. JAMA. 2014;311(1):33-44. doi:10.1001/jama.2013.282834
  8. ↑ Farina N, Llewellyn D, Isaac MG, Tabet N. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2017 Jan 27;1(1):CD002854. doi: 10.1002/14651858.CD002854.pub4. Update in: Cochrane Database Syst Rev. 2017 Apr 18;4:CD002854. PMID: 28128435; PMCID: PMC6464807.