Vitamin E Does Not Prevent Declines in Memory and Cognitive Function

Dietary supplement makers often tout vitamin E products for a variety of purported health benefits, including the promotion of brain health. The vitamin is thought to achieve these benefits because it is an antioxidant, a substance that helps to protect cells from damage.

Over the past two decades, researchers have tested vitamin E supplements in patients with mild cognitive impairment (mild problems with memory and thinking but still able to function) and with Alzheimer’s disease, the leading cause of dementia in the U.S. They had hoped that the antioxidant properties of vitamin E would slow the progression of these disorders by preventing damage to brain cells.

But in April 2017, the Cochrane Database of Systematic Reviews published an updated systematic review of data from randomized, placebo-controlled clinical trials that evaluated the effects of vitamin E in patients with mild cognitive impairment or Alzheimer’s disease. The review found no evidence that vitamin E improves cognitive function in patients with either condition or prevents the progression of mild cognitive impairment to dementia.

Vitamin E facts

Vitamin E is a fat-soluble vitamin that comes in several different forms. The most active form is alpha tocopherol.[1] Vitamin E is found in many foods, including vegetable oils (corn, cottonseed, safflower, soybean and sunflower), olive oil, green leafy vegetables (such as spinach), nuts, whole-grain cereals and egg yolk.[2] Some vitamin E may be lost or destroyed during cooking and storage.

A well-balanced diet with a variety of healthful foods should supply all of the vitamin E that the body needs. The recommended dietary allowance (RDA) of vitamin E is 15 milligrams (mg) [approximately 22 international units (IUs)] per day for most healthy individuals — both male and female — over the age of 13.[3] For women who are breastfeeding, the RDA is 19 mg (about 28 IUs) per day.

Vitamin E deficiency is extremely rare and has not been known to occur solely from an inadequate diet. It occurs mainly in people who have certain conditions of the intestines, pancreas or liver that interfere with the body’s ability to absorb fat-soluble vitamins, which also include vitamins A, D and K.

Cochrane review findings

The authors of the new Cochrane systematic review carefully searched scientific databases for all randomized clinical trials that compared the effects of vitamin E with those of a placebo in patients with mild cognitive impairment or Alzheimer’s disease.[4]

They identified only one trial that tested the effects of vitamin E in patients with mild cognitive impairment. The trial, which was published in the New England Journal of Medicine in 2005, enrolled 769 adults with mild memory problems who had an average age of 73.[5] The subjects were randomly assigned to receive one of the following treatments daily for three years:

• vitamin E, 2,000 IUs;
• donepezil (ARICEPT), a drug approved for treating Alzheimer’s disease, which we have designated as Do Not Use; or
• a placebo.

After three years, 30 percent of the vitamin E group subjects and 28 percent of the placebo group subjects had progressed from mild cognitive impairment to Alzheimer’s disease. In addition, by the end of the study, there were no significant differences between these two groups on stanstandardized tests for memory and other cognitive functions. Based on this data, the Cochrane review authors concluded that there is no evidence that Vitamin E improves cognitive function or reduces the risk of progression to Alzheimer’s disease in people with mild cognitive impairment.

The Cochrane review authors identified three randomized trials that compared the effects of vitamin E with those of a placebo in patients with Alzheimer’s disease. However, only one of these trials provided useful data on cognitive function outcomes. The trial, which was published in the Journal of the American Medical Association (JAMA) in 2014, enrolled 613 patients with mild to moderate Alzheimer’s disease.[6] The subjects were randomly assigned to receive one of the following treatments daily:

• vitamin E, 2,000 IUs;
• memantine (NAMENDA), another drug approved for treating Alzheimer’s disease, which we have designated as Do Not Use;
• both vitamin E and memantine; or
• a placebo.

The Cochrane review authors included in their analysis only data from the first and last groups. After an average follow-up period of slightly more than two years, no significant differences were seen on mental state examinations and other measures of cognitive function between the vitamin E and placebo group subjects. The trial did find that the rate of decline in the ability of subjects to carry out daily activities was slightly lower in the vitamin E group, but this change was not great enough to be clinically important. Based on all the data, the Cochrane review authors concluded that there was little evidence that vitamin E is effective for treating Alzheimer’s disease.

Evidence of harm

Taking vitamin E in doses that far exceed the RDA can be harmful. Some people taking vitamin E supplements at high doses have been reported to suffer muscle weakness, fatigue, dizziness, headaches, nausea, diarrhea, abdominal cramping or high blood pressure.[7]

Vitamin E also may interfere with blood clotting and increase the risk of bleeding.[8] One very large randomized clinical trial found that taking vitamin E (50 mg daily) increased the risk of bleeding in the brain compared with taking a placebo in men who had an increased risk of stroke.[9]

In 2005, the Annals of Internal Medicine published another study that analyzed data from 11 clinical trials evaluating vitamin E supplementation. It found that taking vitamin E in doses of 400 IU or higher per day was associated with an increased risk of death.[10]

Finally, in 2011, JAMA published results of a large randomized clinical trial testing whether vitamin E decreased the risk of prostate cancer. The study showed that vitamin E treatment (400 IU daily) significantly increased the risk of prostate cancer in healthy men.[11]

What You Can Do

For many years, Public Citizen’s Health Research Group has designated vitamin E as a “Do Not Use” dietary supplement. You should not take vitamin E supplements to treat mild cognitive impairment or Alzheimer’s disease because there is no evidence of significant benefit, but there is extensive evidence of significant risk.

References

[1] Mayo Clinic. Drugs and supplements: Vitamin E. http://www.mayoclinic.org/drugs-supplements/vitamin-e/background/hrb-20060476. Accessed August 7, 2017.

[2] Ibid.

[3] The National Academies of Sciences, Engineering, and Medicine. Dietary reference intakes (DRIs): Recommended dietary allowances and adequate intakes, vitamins. http://www.nationalacademies.org/hmd/~/media/Files/Activity%20Files/Nutrition/DRI-Tables/2_%20RDA%20and%20AI%20Values_Vitamin%20and%20Elements.pdf?la=en. Accessed August 7, 2017.

[4] Farina N, Llewellyn D, Isaac MG, Tabet N. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2017, Issue 1. Art. No.: CD002854.

[5] Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379-2388.

[6] 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. JAMA. 2014;311(1):33-44.

[7] Roberts HJ. Perspective on vitamin E as therapy. JAMA. 1981;246(2):129-131.

[8] Stanger MJ, Thompson LA, Young AJ, Lieberman HR. Anticoagulant activity of select dietary supplements. Nutr Rev. 2012 Feb;70(2):107-117.

[9] Leppälä JM, Virtamo J, Fogelholm R, et al. Vitamin E and beta carotene supplementation in high risk for stroke: A subgroup analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Arch Neurol. 2000;57(10):1503–1509.

[10] Miller ER, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37-46.

[11] Klein EA, Thompson IM, Tangen CM, et al. Vitamin E and the risk of prostate cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.