Can a high dose vitamin E supplementation delay the onset of Alzheimer’s disease?

A recent study by Professor Maurice Dysken of the University of Minnesota Medical School provides data that indicates that high dose vitamin E supplementation could be useful as a therapeutic treatment to delay the onset of Alzheimer’s disease.

Alzheimer’s disease (AD) was first described by the German doctor Alois Alzheimer in 1907. The disease leads to a build-up of fragments of beta-amyloid and intercellular hyperphosphorylated tau strands in the brain. AD leads to progressive cognitive impairment and finally death within ten years of diagnosis. Currently, there is no effective treatment or means of preventing the onset of the condition.

Current therapeutic research concentrates on slowing the progress of the disease. The Alzheimer’s Association say that in 2015 5.3 million Americans currently have the disease, and this level is predicted to triple by 2050. Age and family history are probably the most important risk factors, but lifestyle factors such as lack of exercise, obesity, smoking, lack of education, high blood pressure, depression and elevated homocysteine levels are also important.

Mild cognitive impairment (MCI) is common in people aged over 60 years, but 12-15% of the sufferers of this condition will progress to full blown Alzheimer’s disease.

There is now some evidence that nutrients could play a role in delaying the onset of cognitive decline. Higher intakes of vitamins and minerals, consumed as foods or supplements, are associated with lower risk of developing cognitive deficits, whilst blood serum levels for folate, vitamin A, B6, vitamin B12, C, E, D, K, thiamine, β-carotene & DHA tend to be lower in AD patients. Anti-oxidant activity of these nutrients is likely to play a role. It is therefore concerning to find vitamin E levels are 75% below the recommended levels in the USA and UK.

Current pharmacological treatment to temporarily slow down the progression of mild to severe AD involves two classes of drugs:

1. Acetyl cholinesterase (AChEI) inhibitors (e.g., donepezil) which helps main acetyl choline levels in the brain.

2. NMDA (N-methyl-D aspartate) receptor antagonists (e.g., memantine) which activate ion channel proteins found in nerve cell membranes.

In 1997, Sano et al. looked at the effect of vitamin E and selegiline in a cohort of 341 patients with moderately severe Alzheimer’s disease which showed that vitamin E supplementation alone delayed the progression of AD by about seven months over a two year follow-up period, which was more than selegiline or a combination of both. (Selegiline was used in the past as a treatment for cognitive decline and is still used in some treatments for Parkinson’s disease. It is a monoamine oxidase type B inhibitor allowing increased production of dopamine and phenylethylamine in the brain).

However, a randomized controlled trial (RCT) in 2005, by Petersen et al. did a trial with vitamin E and donepezil in cohort of 769 with mild cognitive impairment patients which showed neither therapy was beneficial over a three year period, though donepezil was shown to reduce conversion to AD over a one to two year period which was consistent with previous trials.

The recent Dysken RCT, monitored a cohort of 613 patients with mild to moderate AD over an average 2.3 year period. One intervention arm was given 1,000 IU of vitamin E was twice a day, whilst another was given 20mg/d memantine. There were also combination treatment and control arms. The vitamin E group showed a delay in progression of AD of 19% in comparison with the control group (i.e., an effective delay of 6.2 months). The total amount of caregiver time also expended was least in the vitamin E intervention group. Again, the vitamin E alone therapy achieved superior results to the memantine or combined therapy. As an addition advantage, there was less mortality in the vitamin E only group.

In summary, a new RCT demonstrates that high dose vitamin E supplementation (2,000 IU per day) can be effective when used alone to delay the progression of mild to moderate Alzheimer’s disease but should not be used in combination with existing drug therapies. Clearly further studies need to be done to confirm these exciting results.

1. Dysken M, Sano M et al., Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease: The TEAM-AD VA Cooperative Randomized Trial, JAMA 2014, 311(1)33–44.
2. Mohajeri H, Troesch B & Weber P, Inadequate supply of vitamins and DHA in the elderly: implications for brain aging and Alzheimer-type dementia, Nutrition 2015, 31(2):261–275.
3. Troesch B, Hoeft B, et al., Dietary surveys indicate vitamin intakes below recommendations are common in representative Western countries, British Journal of Nutrition 2012, 108 (4): 692–698.
4. Sano M, Ernesto C, Thomas RG, et al. 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. 1997; 336(17): 1216–1222.
5. Petersen RC, Thomas RG, Grundman M, et al; Alzheimer’s Disease Cooperative Study Group. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005; 352(23): 2379–2388.