Study shows benefit in activities of daily living and savings in caregiver time with vitamin E

Difficulty with activities of daily living often affect Alzheimer's patients, which is estimated to affect as many as 5.1 million Americans. These issues are among the most taxing burdens of the disease for caregivers, which total about 5.4 million family members and friends. New research from the faculty of Icahn School of Medicine at Mount Sinai working with Veterans Administration Medical Centers suggests that alpha tocepherol, fat-soluble Vitamin E and antioxidant, may slow functional decline (problems with daily activities such as shopping, preparing meals, planning, and traveling) in patients with mild-to-moderate Alzheimer's disease and decrease caregiver burden. There was no added benefit for memory and cognitive testing with the vitamin. The study is published online first in the Jan. 1 Journal of the American Medical Association.

06 Jan 2014--"Since the cholinesterase inhibitors [galantamine, donepezil, rivastigmine], we have had very little to offer patients with mild-to-moderate dementia," said Mary Sano, PhD, trial co-investigator, and professor in the department of psychiatry, Icahn School of Medicine at Mount Sinai, and director of research at the James J. Peters Veteran's Administration Medical Center, Bronx, New York. "This trial showed that vitamin E delays progression of functional decline by 19% per year, which translates into 6.2 months benefit over placebo."

The finding is valuable because vitamin E is easy to purchase at local drugstores and it is also inexpensive. The clinical trial investigators believe it can be recommended as a treatment strategy, based on the double-blind randomized controlled trial.

The Veteran's Administration Cooperative Randomized Trial of Vitamin E and memantine in Alzheimer's Disease (TEAM-AD examined the effects of vitamin E 2,000 IU/d, 20 mg/d of memantine, the combination, or placebo on Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory Score. Cognitive, neuropsychiatric, functional, and caregiver measures were secondary outcomes. A group of 613 patients with mild to moderate Alzheimer's disease were in the study, which was launched in August 2007 and finished in September 2012 at 14 Veterans Affairs Medical Centers.

Dr. Sano previously led a study on vitamin E in patients with moderately severe Alzheimer's disease. She found that the vitamin slowed disease progression in this group of patients as well.

Kenneth Davis, MD, Chief Executive Officer and President of the Mount Sinai Health System and Gustave L. Levy Distinguished Professor, applauded the study. "This study is the first to show an added benefit for vitamin E in mild-to-moderate disease," he said. "Now that we have a strong clinical trial showing that vitamin E slows functional decline and reduces the burdens on caregivers, vitamin E should be offered to patients with mild-to-moderate Alzheimer's disease." Research by Dr. Davis and colleagues contributed to the establishment of conventional medical therapies for Alzheimer's disease.

More information: doi:10.l001/jama.2013.282834 and doi:10.l001/jama.2013.282835

Provided by The Mount Sinai Hospital

Scientists identify an innate function of vitamin E

Dr. Paul McNeil, cell biologist at Georgia Health Sciences University, has discovered one of the innate functions of vitamin E. Credit: Phil Jones/GHSU photographer

It's rubbed on the skin to reduce signs of aging and consumed by athletes to improve endurance but scientists now have the first evidence of one of vitamin E's normal body functions.

28 dec 2011--The powerful antioxidant found in most foods helps repair tears in the plasma membranes that protect cells from outside forces and screen what enters and exits, Georgia Health Sciences University researchers report in the journal Nature Communications.

Everyday activities such as eating and exercise can tear the plasma membrane and the new research shows that vitamin E is essential to repair. Without repair of muscle cells, for example, muscles eventually waste away and die in a process similar to what occurs in muscular dystrophy. Muscle weakness also is a common complaint in diabetes, another condition associated with inadequate plasma membrane repair.

"Without any special effort we consume vitamin E every day and we don't even know what it does in our bodies," said Dr. Paul McNeil, GHSU cell biologist and the study's corresponding author. He now feels confident about at least one of its jobs.

Century-old animal studies linked vitamin E deficiency to muscle problems but how that happens remained a mystery until now, McNeil said. His understanding that a lack of membrane repair caused muscle wasting and death prompted McNeil to look at vitamin E.

Vitamin E appears to aid repair in several ways. As an antioxidant, it helps eliminate destructive byproducts from the body's use of oxygen that impede repair. Because it's lipid-soluble, vitamin E can actually insert itself into the membrane to prevent free radicals from attacking. It also can help keep phospholipids, a major membrane component, compliant so they can better repair after a tear.

For example, exercise causes the cell powerhouse, the mitochondria, to burn a lot more oxygen than normal. "As an unavoidable consequence you produce reactive oxygen species," McNeil said. The physical force of exercise tears the membrane. Vitamin E enables adequate plasma membrane repair despite the oxidant challenge and keeps the situation in check.

When he mimicked what happens with exercise by using hydrogen peroxide to produce free radicals, he found that tears in skeletal muscle cells would not heal unless pretreated with vitamin E.

Next steps, which will be aided by two recent National Institutes of Health grants, include examining membrane repair in vitamin E-deficient animals.

McNeil also wants to further examine membrane repair failure in diabetes. Former GHSU graduate student Dr. Amber C. Howard showed in a recent paper in the journal Diabetes that cells taken from animal models of types 1 and 2 diabetes have faulty repair mechanisms. Howard found high glucose was a culprit by soaking cells in a high-glucose solution for eight to 12 weeks, during which time they developed a repair defect. It's also well documented that reactive oxygen species levels are elevated in diabetes.

The Nature Communications paper showed that vitamin E treatment in an animal model of diabetes restored some membrane repair ability. Also, an analogue of the most biologically active form of vitamin E significantly reversed membrane repair deficits caused by high glucose and increased cell survival after tearing cells in culture.

Now McNeil wants to know if he can prevent the development of advanced glycation end products – a sugar that high glucose adds to proteins that his lab has shown can also impede membrane repair – in the animal models of diabetes. The researchers have a drug that at least in cultured animal cells, prevents repair defects from advanced glycation end products.

Provided by Georgia Health Sciences University

Vitamin E Offers No Protection from Cataracts

By John Gever
BOSTON, 04 may 2008-- Ten years of vitamin E supplements were associated with no effect on cataract development among middle-age and older women, researchers here found.
Among 37,675 participants in the Women's Health Study, involving women 45 and older, 1,159 of those taking vitamin E supplements and 1,217 of those taking placebo developed cataracts, reported William G. Christen, D.Sc., of Brigham and Women's Hospital, and colleagues in the May issue of Ophthalmology.
That worked out to a relative risk of 0.96 (95% CI 0.88 to 1.04), the researchers said.
The Women's Health Study randomized health professionals to 600 IU of vitamin E or placebo every other day, and to 100 mg of aspirin or placebo every other day. Early participants also took beta-carotene. The primary endpoints involved cardiovascular events and cancer. The study began in 1993 and is ongoing.
Because cataracts are thought to arise from oxidative damage to the lens, a number of prospective trials have examined whether vitamin E supplements can prevent them.
None of them identified a benefit, but the longest follow-up in those studies was 6.5 years. Cataracts are slow to develop, and finding a benefit from vitamin E may require a longer trial, Dr. Christen and colleagues said.
Mean follow-up in the Women's Health Study was 9.7 years, with data through March 2004 analyzed in the study.
Participants completed annual questionnaires, which included an item asking whether they had a new diagnosis of cataract or had undergone a cataract extraction.
Those with "yes" answers were asked to give consent for their ophthalmologists or optometrists to be consulted. These professionals then were asked to submit detailed information on the participants' diagnosis and treatment.
Dr. Christen and colleagues obtained adequate information for more than 91% of participants reporting new cataracts.
The data failed to show any effect of vitamin E on subgroups of participants, stratified by age or type of cataract (nuclear sclerosis, cortical, or posterior subcapsular).
Nor did stratification by risk factor reveal a benefit for vitamin E.
Risk factors analyzed in the study included smoking status, alcohol use, body mass index, hypertension, hyperlipidemia, diabetes, menopausal status, use of hormone replacement therapy, parental history of early heart attack, and current multivitamin use.
The only risk-factor subgroups that came close to a significant benefit from vitamin E were those with a parental history of early heart attack (RR 0.80, P=0.08), those with body mass index less than 25 (RR 0.91, P=0.10), and those with hypertension (RR 0.91, P=0.16).
Dr. Christen and colleagues said the apparent lack of effect, while consistent with earlier trials, does not absolutely rule out the possibility that anti-oxidant treatment could help prevent cataracts.
Other researchers have suggested that a barrier forms by middle age that prevents anti-oxidant molecules from reaching the lens nucleus.
"If real, such a barrier might have contributed to the null findings," Dr. Christen and colleagues wrote.
Poor participant compliance seemed unlikely to explain the findings. Thus "averaged throughout the trial, compliance (defined as taking at least two-thirds of the study capsules) was 75.8%, with no difference between the active and placebo groups (P=0.64)," they wrote.
Confounding factors not taken into account in the study design and bias in measuring cataract formation were also possible, though unlikely, the researchers said.
Dr. Christen and colleagues noted that several large ongoing trials are also testing anti-oxidants for preventing eye disease, including the Physicians' Health Study II, a male counterpart to the Women's Health Study.
Data from the large Nurses' Health Study in 2005 found that participants taking vitamin E supplements had slower progression of cataracts. However, that was a retrospective analysis derived from nutrient intake questionnaires, and participants decided on their own whether to take supplements.
The Women's Health Study analysis was funded by the National Institutes of Health. The Women's Health Study is sponsored by the National Heart, Lung, and Blood Institute.
No potential conflicts of interest were reported.

Primary source: OphthalmologySource reference:Christen W, et al "Vitamin E and age-related cataract in a randomized trial of women" Ophthalmology 2008; 115: 822-29.

Myth of Vitamin E Benefits Perpetuated in Peer-Reviewed Journals


IOANNINA, Greece, Dec. 5 -- Although randomized clinical trials have discredited any purported cardiovascular benefits of vitamin E, peer-reviewed medical journals keep citing old disproved epidemiologic findings, found researchers here.
Action Points --->
Explain to interested patients that this study found that articles in the literature continue to cite the protective benefits of vitamin E, beta-carotene, and estrogen for cardiovascular disease, cancer, and Alzheimer's disease, respectively, even though strong evidence from clinical trials has found otherwise.
That emerged from an analysis of citation patterns in journal articles published before, soon after, and several years after the vitamin E claims were contradicted, John P.A. Ioannidis, M.D., of the University of Ioannina School of Medicine, and colleagues, reported in the Dec. 5 issue of the Journal of the American Medical Association.
They said the same pattern -- citing observational findings from epidemiologic studies that have been solidly countered by randomized trials -- also continued for studies of beta-carotene and estrogen.
This trend wastes time, effort, and money and can "also perpetuate a literature of false impressions that can affect future scientific efforts by providing a misleading starting base," said Dr. Ioannidis and colleagues. They did not cite the offending journals by name.
Two articles touting the benefits of vitamin E were published in 1993, but the HOPE trial, which was published in 2000, found that vitamin E did not reduce the risk of cardiovascular events.
A favorable finding for vitamin E was less likely in papers published in 2005 than in 2001 or 1997 (P<0.001), yet half of the 46 vitamin E studies published in 2005 cited the two 1993 papers as evidence of the benefit of vitamin E, Dr. Ioannidis and colleagues said.
Moreover, when researchers analyzed 29 articles published in 2005 that cited the HOPE trial, 20.7% of those were still favorable to vitamin E's role in cardiovascular protection, 37.9% were equivocal, and 41.4% were unfavorable.
The researchers found an even higher rate of erroneous claims for articles on beta-carotene and estrogen.
Clinical trials published in 1994 and 1996 found no evidence that beta-carotene supplements prevent cancer, but 10 of 16 articles published in 2006 cited a 1981 review of epidemiology research, which suggested the antioxidant may help reduce the risk of developing the disease. The remaining six articles were evenly divided between equivocal and unfavorable.
For estrogen, 61.7% of 47 articles published in 2006 indicated the hormone may protect against Alzheimer's disease on the basis of a 1996 observational study, even though a clinical trial in 2004 found a trend for increased risk of dementia in postmenopausal women taking estrogen. Of the remaining articles, 29.8% were equivocal, and 8.5% were unfavorable.
Articles that espoused beta-carotene's cancer preventive effect did not consider contradicting evidence, but many of the studies touting the positive benefits of vitamin E or estrogen included counterarguments for why the clinical trial findings did not hold, including information biases or differences in study participants, interventions, co-interventions, and outcomes measured.
The possibility that some of these counterarguments are valid cannot be fully excluded and poses one limitation for the study, Dr. Ioannidis said. However, he added, the more likely scenario is that these researchers have a "wish bias" and are unwilling to let go of their hypotheses, even when the contradicting evidence is overwhelming.
One way of improving this situation is for researchers who specialize in very narrow fields, such as specific vitamins or hormones, to communicate more with those in clinical science and evidence-based medicine, Ioannidis said. "This communication may improve the rational design of translational research efforts to find effective treatments," he said.
Christian Gluud, M.D., of Copenhagen University Hospital in Denmark, said he thinks this pattern of not accepting the findings of randomized clinical trials when they refute epidemiological studies happens in other areas beyond vitamins and hormones.
"I don't think they've identified a rare behavior," Dr. Gluud said in an interview. "I think what they've identified is the norm." Dr. Gluud was not involved in the study.
In addition to spurring research that is based on false premises, the practice could also harm the public, Dr. Gluud said. If the general population picks up on the erroneous results, people could jump the gun and start taking vitamin supplements for diseases for which they have not been shown to be effective or safe, he said.
The researchers reported no financial conflicts of interest and no funding source was reported.
Primary source: Journal of the American Medical AssociationSource reference:Tatsioni A, et al "Persistence of contradicted claims in the literature" JAMA 2007; 298: 2517-2526.