Antioxidants May Not Help Alzheimer's Patients
Vitamin cocktail might even speed up mental decline, researchers say
March 19, 2012
Researchers have suggested that antioxidants might help thwart Alzheimer's disease, but a new study finds that a "cocktail" of vitamins E, vitamin C and alpha-lipoic acid has no effect on certain indicators of the brain disorder.
The supplements may even have hastened mental decline, the researchers said.
"The benefit on oxidative stress in the brain was small and is of unclear significance," said lead researcher Dr. Douglas Galasko, a professor in residence in the department of neurosciences at the University of California, San Diego.
"Patients did not show cognitive improvement in this short-term study; in fact, there was a slight worsening on one test of cognition in patients who received the antioxidant combination," Galasko said.
Aging causes oxidative damage in the brain, which is extensive in people with Alzheimer's disease. Clinical trials looking at whether a diet rich in antioxidants could reduce that risk have had mixed results, the researchers said.
This study does not support using any of these antioxidants once a diagnosis is made of established Alzheimer's disease, Galasko said. "If antioxidants continue to be tested against Alzheimer's disease, newer approaches or drugs may be needed," he said.
This study, published in the March 19 online edition of the Archives of Neurology, does not address whether taking antioxidants could help to prevent Alzheimer's disease, he noted. Alzheimer's disease is the most common form of dementia among older people.
For the study, Galasko's team gave antioxidant supplements to 78 patients with Alzheimer's disease who were part of a study funded by the U.S. National Institute on Aging. The patients were placed into three groups. One group received daily doses of vitamin E, vitamin C and alpha-lipoic acid. A second group was given coenzyme Q (a compound made naturally in the body to protect cells from damage) three times a day. The third group received a placebo. After 16 weeks, 66 patients had their cerebrospinal fluid analyzed.
Among the three groups, the researchers found no difference in markers related to Alzheimer's disease in the cerebrospinal fluid. These markers included the amyloid-beta protein and the proteins tau and P-tau.
Galasko's group did see lower levels of one marker called F2-isoprostane, which could indicate a reduction in oxidative stress in the brain. However, the use of vitamins might have increased the pace of the disease, causing faster decline in mental ability, they cautioned.
Greg Cole, associate director of the Alzheimer's Disease Research Center at the University of California, Los Angeles David Geffen School of Medicine, said that vitamin E alone has shown some limited benefits in Alzheimer patients, but with no evidence that it really works to reduce oxidative damage, and that alpha lipoate -- a form of alpha-lipoic acid -- alone has also had some reported benefits, he said.
"Unfortunately, these researchers found no impact on pathological protein levels, and in their small group of patients, their cognitive function actually declined more than in the placebo group," Cole noted.
The increased cognitive decline might be due to random variation, he said, "or it may be a surprising but real adverse effect from something as seemingly innocuous as an antioxidant cocktail."
His research group has seen similar adverse effects from some, but not all, antioxidant mixes, he said.
"This should be a caution to the supplement manufacturers who typically sell products throwing in some mix of what seems like a great group of sensible antioxidants," he added. "Everyone assumes that they will work well together and are good for you, but they don't test them."
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http://archneur.ama-assn.org/cgi/content/abstract/archneurol.2012.85v1
Antioxidants for Alzheimer Disease
A Randomized Clinical Trial With Cerebrospinal Fluid Biomarker Measures
Douglas R. Galasko, MD; Elaine Peskind, MD; Christopher M. Clark, MD; Joseph F. Quinn, MD; John M. Ringman, MD; Gregory A. Jicha, MD, PhD; Carl Cotman, PhD; Barbara Cottrell, BS; Thomas J. Montine, MD, PhD; Ronald G. Thomas, PhD; Paul Aisen, MD; for the Alzheimer's Disease Cooperative Study
Arch Neurol. Published online March 19, 2012. doi:10.1001/archneurol.2012.85
Objective To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers.
Design Double-blind, placebo-controlled clinical trial.
Setting Academic medical centers.
Participants Subjects with mild to moderate Alzheimer disease.
Intervention Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo.
Main Outcome Measures Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer's Disease Cooperative Study Activities of Daily Living Scale).
Results Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aβ42, tau, and P-tau181 levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups.
Conclusions Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted.
Trial Registration clinicaltrials.gov Identifier: NCT00117403
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