Two thousand international units per day of vitamin E was associated with a delay in clinical progression of 19% per year, compared with placebo, according to findings published in JAMA.
In addition, the study – one of the largest and longest treatment trials in patients with mild to moderate Alzheimer’s disease – supports the safety of vitamin E supplements.
“In contrast to the conclusion drawn from a 2005 meta-analysis of vitamin E, which showed that high-dose vitamin E (at least 400 IU/d) may increase the risk of all-cause mortality, we found no significant increase in mortality with vitamin E,” wrote the researchers. “The annual mortality rate was 7.3 percent in the alpha tocopherol group vs. 9.4 percent for the placebo group.”
Duffy MacKay, ND, vice president, scientific and regulatory affairs for the Council for Responsible Nutrition (CRN), welcomed the study’s findings, saying: “This study is significant as it presents strong data on the safety of vitamin E, at high doses, and dismisses previous questions raised about the safety of this essential nutrient. This new study demonstrates that scientists seeking to slam the door on vitamins, and new vitamin research, is the antithesis of what science is all about.
“In addition to confirming the safety of vitamin E, this study, one of the largest and longest treatment trials in patients with mild to moderate Alzheimer’s disease, found 2000 IU/daily of vitamin E compared with placebo resulted in slower functional decline in these patients. These results point to a powerful role of integrating proper nutrition into disease management, and provide hope for Alzheimer’s patients and their care givers.
“However, the dietary supplement industry should be reminded that dietary supplements cannot be marketed or sold to consumers as a disease treatment, and we recommend that those suffering with Alzheimer’s disease rely on the advice of a trusted doctor as to the appropriate treatment plan. Self-dosing at the levels studied in this trial are not recommended.
“It is commendable that aspects of this study ‘reflect the best in trials of Alzheimer disease therapy,’ as noted in an accompanying editorial, though we still encourage more research to further assess the role vitamin E plays in both the prevention and treatment of this very complicated disease.”
Researchers led by Maurice Dysken, MD, of the Minneapolis VA Health Care System, recruited 613 patients with mild to moderate Alzheimer’s to participate in their randomized clinical trial. The participants were randomly assigned to one of four groups: The first group received 2000 IU/d of vitamin E, the second group received 20 mg per day of memantine (an Alzheimer's disease medication), the third group received a combination of vitamin E and memantine, and the last group received placebo.
Data from the 561 participants who completed the study indicated that, over almost 2.5 years, the vitamin E group displayed slower functional decline equivalent to a clinically meaningful delay in progression of 6.2 months, compared with placebo. No benefits were observed in the memantine only or the vitamin E-memantine combination groups.
The study also supported the safety of vitamin E at a dose of 2000 IU per day.
On the other hand, significant increases in serious adverse events of “infections or infestations” were observed in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants), compared with placebo.
“In the current study, the placebo group lost approximately 3 units more on the [Alzheimer’s Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory] than the alpha-tocopherol group,” wrote the researchers.
“A loss of this magnitude could translate into either the complete loss of being able to dress or bath independently, for example, or losing independence on any 3 different [Activities of Daily Living]. Because vitamin E is inexpensive, it is likely these benefits are cost-effective as alpha tocopherol improves functional outcomes and decreases caregiver burden.”
Treatment vs preventions
In an accompanying editorial in JAMA, Denis Evans, MD, Martha Clare Morris, ScD, and Kumar Bharat Rajan, PhD, from Rush University Medical Center in Chicago, wrote: “Many features of the trial by Dysken et al reflect the best in trials of Alzheimer’s disease therapy, especially its size, duration, and separation from commercial motivation. However, as with almost all previous Alzheimer’s disease trials, the therapeutic effect seen was modest and more relevant to Alzheimer’s disease symptoms and consequences than to reversal of the disease process. The importance of treating patients with Alzheimer’s disease is clear, but finding the best balance between treatment and prevention efforts is challenging for this grim disease affecting millions of people from all developed countries.”
“Considering the difficulties inherent in trying to treat rather than prevent very high-prevalence diseases and the limitations thus far of the therapeutic efforts for people with Alzheimer’s disease, shifting to more emphasis on prevention seems warranted.”
2014, Volume 311, Number 1, Pages 33-44, doi:10.1001/jama.2013.282834
“Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease - The TEAM-AD VA Cooperative Randomized Trial”
Authors: M.W. Dysken, M. Sano, S. Asthana, et al.
2014, Volume 311, Number 1, Pages 29-30, doi: 10.1001/jama.2013.282835
“Vitamin E, Memantine, and Alzheimer Disease”
Authors: D.A. Evans, M.C. Morris, K.B. Rajan