Antioxidants may not benefit patients with Alzheimer's disease

Daily supplementation with antioxidants, vitamins E and C, and alpha acid (ALA), did not improve memory function in patients with Alzheimer’s disease (AD), according to a new study.

In fact, researchers who conducted the study, published in the Archives of Neurology, noted a faster decline as measured with the Mini-Mental State Examination (MMSE).

“Antioxidant randomized clinical trials in AD have had mixed results,” stated the researchers, led by Douglas Galasko, MD, from the University of California, San Diego. “We hypothesized that if antioxidant treatment affects key pathogenic mechanisms in patients with AD, this would be reflected by cerebrospinal fluid (CSF) biomarker changes.”

The researchers randomly assigned 78 patients with mild-to-moderate Alzheimer's disease, seen at 12 different medical centers, to 1 of 3 different supplement groups:

A daily combination of vitamin C (500 mg/d), vitamin E (800 IU/d), and ALA (900 mg/d) administered 3 times per day.

Coenzyme Q (CoQ; 400 mg) 3 times per day.

Placebo administered 3 times per day.

The primary outcome measures were levels of 4 biochemical markers measured in CSF: Aβ42, a 42–amino acid peptide that leads to plaques on the brain of patients with AD; tau and tau phosphorylated (P-tau), which relate to neuron damage; and F2-isoprostane levels, which relates to oxidative damage to the central nervous system.

The researchers comparatively assessed cognition with the MMSE at baseline and 16 weeks as well as functional abilities rated by an informant interview using the ADCS Activities of Daily Living Scale (ADCS-ADL).

They found that patients taking vitamins E and C and ALA showed greater decline in cognitive abilities compared to patients taking placebo. Patients taking vitamins E and C and ALA showed a small but significant mean 19% decrease from baseline in levels of F2-isoprostane, suggesting a decrease in oxidative stress in the brain.

The researchers also noted that it is not clear whether this small reduction could have any clinical impact in AD. There was no change for patients taking CoQ or placebo. And the combination of vitamins E and C and ALA did not affect CSF biomarkers related to Aβ, tau, or P-tau.

“Increased decline on the MMSE and a trend in this direction on the ADCS-ADL in the E/C/ALA group raises a concern that this combination could adversely affect cognition in AD,” the researchers wrote.

“The lack of correlation of changes in these measures with changes in CSF biomarkers suggests that the cognitive changes may not be due to worsening of AD-related pathology. Although a mechanism is uncertain, this cognitive finding raises a caution and will need to be carefully monitored if longer-term studies are planned.”