Long-Term Vitamin E Intake Linked to Reduced ALS Risk

Pauline Anderson

March 29, 2011

March 29, 2011 — Taking vitamin E supplements for more than 5 years or consuming a diet rich in this vitamin is associated with reduced risk for amyotrophic lateral sclerosis (ALS), according to a pooled analysis of data on more than 1 million participants in 5 prospective studies.

Although the results are promising and support the hypothesis that long-term intake of vitamin E reduces the risk for ALS, it's too early to make any changes in the recommended daily allowance (RDA) for vitamin E, said lead study author Éilis O'Reilly, ScD, research associate in the Department of Nutrition at Harvard School of Public Health, Boston, Massachusetts.

"We may not be at the point yet where a recommendation can be made," said Dr. O'Reilly in an email to Medscape Medical News. "Indeed, it is hard to know who to make such a recommendation to, given that ALS is such a rare disease."

The study appeared in the March 15 issue of the American Journal of Epidemiology.

Five Major Cohorts

The analysis included data from 5 major ongoing cohort studies, including the Nurses' Health Study (NHS, 1976-2004), the Health Professionals Follow-up Study (HPFS, 1986-2004), the Cancer Prevention Study II Nutrition Cohort (CPS II Nutrition, 1992-2004), the Multiethnic Cohort Study (MEC, 1993-2005), and the National Institutes of Health–AARP Diet and Health Study (NIH-AARP, 1995-2005).

All of these studies were included because each on its own had too few cases to make definitive statements about observed associations, said Dr. O'Reilly.

Information on nutrient intake and use of multivitamins and vitamin E supplements, including frequency of use and dosage, was gathered through questionnaires.

For participants who reported a diagnosis of ALS, researchers requested permission for release of relevant medical records. The treating neurologist was asked to confirm a diagnosis of ALS; confirmation was also made by an in-house neurologist based on a review of medical records.

ALS deaths were identified through the National Death Index. In the NHS and the HPFS, confirmed nonfatal ALS cases were also included.

Among 1,055,546 participants (545,377 men), 805 developed ALS during the follow-up period, which ranged from 10 to 18 years.

Overall, using vitamin E supplements was not associated with ALS; among participants who consumed at least 400 IU/day, the adjusted pooled relative risk (RR) was 1.18 (95% confidence interval [CI], 0.83 – 1.67; P = .35) compared with nonusers.

Duration of Supplement Use

However, within cohorts with information on duration of vitamin E supplement use (231 cases included in the NHS, HPFS, and MEC), ALS rates decreased the more years the supplements were used (P for trend = .01).

Table. Risk for Amyotrophic Lateral Sclerosis by Duration of Vitamin E Use vs Nonusers

Duration of Use Adjusted RR (95% CI)
≤1 year (12 cases) 1.05 (0.60 – 1.84)
2-4 years (7 cases) 0.77 (0.33 – 1.77)
≥5 years (18 cases) 0.64 (0.39 – 1.04)

CI = confidence interval; RR = relative risk

For dietary vitamin E intake, the adjusted RR comparing the highest quartile with the lowest was 0.79 (95% CI, 0.61 – 1.03); an inverse dose response was evident in women (P for trend = .002) but not in men (P for trend = .71).

Foods rich in vitamin E include oils, nuts, spinach, and avocado. Dr. O'Reilly explained that dietary and supplemental vitamin E can be different in terms of the isoforms of the compound, so they may have differing biological effects.  

The current average RDA for vitamin E is 15 mg (22.4 IU) daily for men and women and 19 mg (28.4 IU) for breastfeeding women.

The researchers attempted to ensure that the association between long-term vitamin E intake and ALS was not due to study participants starting to take vitamin E after they developed symptoms of ALS. All the analyses were prospective, so they included only those subjects who were taking vitamin E before they had been diagnosed as having ALS.  

"However, some people may have had symptoms of undiagnosed ALS at the start of the study, when we assessed their vitamin E," said Dr. O'Reilly. "In secondary analyses, we excluded ALS cases that happened in the 4 years after the study began, which reduces the chances of including people who started vitamin E because they experienced symptoms."

She added that if people started using vitamin E because of symptoms, she and her colleagues would find that the vitamin was a risk factor rather than a protective factor.

There appear to be few side effects of excessive vitamin E intake, although toxicity studies have not been long term, said Dr. O'Reilly. "One known concern is that vitamin E can interfere with clotting mechanisms, so some people may experience increased risk of hemorrhage."   

The study found no evidence that smoking, sex, or vitamin C intake modified the results.

The researchers concluded that a possible protective effect of vitamin E deserves further consideration. In the meantime, Dr. O'Reilly stressed that the findings are not definitive and should not spur patients to up their vitamin E intake just to prevent ALS.  

"In terms of supplements, it's important to remember that more is not always better and to adhere to RDA guidelines and that decisions on supplement use should consider the overall health benefit, rather than focusing on 1 particular rare disease like ALS."

She also noted that unlike the situation with common diseases, such as coronary heart disease or diabetes, public health recommendations are not often made for rare diseases such as ALS. 

Mixed Results

Asked for a comment, Thomas M.S. Wolever, PhD, professor in the Department of Nutritional Sciences in the Faculty of Medicine at the University of Toronto, Ontario, Canada, stressed that the associations uncovered by the study don't prove causality.

This all needs to be interpreted with a huge amount of caution.

He noted that studies of vitamin E have had mixed results. "Similar studies show that the use of vitamin E is associated with large risk reductions in risk for heart attacks — but several large, randomized, controlled, clinical trials of vitamin E have shown absolutely no effect," he said in an email to Medscape Medical News.

At the end of the day, he added, "this all needs to be interpreted with a huge amount of caution."

The study authors have disclosed no relevant financial relationships.

Am J Epidemiol. 2011;173:595-602.

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