Interesting findings

[Guest guest]

Docs:

Here are some interesting findings regarding antioxidants and

Alzheimer's.

Lyndon McGill, D.C.

EvolvHealth Wellness Advisory Council Member

Salem, Oregon

www.SalemSpineClinic.com

www.EvolvingDaily.com

Antioxidant Study in Alzheimer’s Raises Red Flag

March 19, 2012 — The antioxidant combination of vitamin E,

vitamin C, and alpha-lipoic acid (ALA) did not alter cerebrospinal

fluid (CSF) biomarkers related to amyloid and tau pathology in a

16-week study of patients with mild to moderate Alzheimer's

disease (AD).

The antioxidant combination led to a relatively small reduction

in CSF F2-isoprostane level, suggesting a decrease in oxidative

stress in the brain, but it was also associated with accelerated

cognitive decline on the Mini-Mental State Examination (MMSE).

"It is unclear whether the relatively small reduction CSF

F2-isoprostane level seen in this study may lead to clinical

benefits in AD," the authors say. In addition, the more rapid MMSE

score decline "raises a caution and indicates that cognitive

performance would need to be assessed if a longer-term clinical

trial of this antioxidant combination is considered," they add.

The study also failed to find any beneficial effect of high-dose

coenzyme Q (CoQ) on CSF biomarkers. "These results do not support

further clinical trial development of CoQ in AD," the authors say.

R. Galasko, MD, of the University of California, San

Diego, and colleagues reported their findings March 19 in Archives

of Neurology.

Data 'Extremely Useful'

In an email to Medscape Medical News, Nikolaos

Scarmeas, MD, MSc, associate professor of neurology, Columbia

University Medical Center in New York City, who was not involved

in the study, said: "It is a negative study but extremely useful

in many ways. It is trying to demonstrate whether there are truly

the expected antioxidant effects in central nervous system when a

series of antioxidant supplements are administered to patients

with AD."

"Unfortunately," Dr. Scarmeas noted, "the clinical data seem to

move in opposing directions to the biomarker (data): CoQ did not

seem to reduce biomarkers of oxidative stress in CSF, while the

combination of vitamins C, E, and alphalipoic acid did so, but did

not affect AD-related biomarkers and accelerated cognitive

decline. But even this is quite informative."

Oxidative damage is associated with aging and is widespread in

the brain in AD, Dr. Galasko and colleagues note in their article.

Basic and observational studies provide strong support for

antioxidant treatment in AD yet randomized controlled trials have

yielded mixed results.

The researchers hypothesized that if antioxidant treatment

affects key pathogenic mechanisms in AD, this would be reflected

in CSF biomarker changes. To investigate, they studied 78 adults

with mild to moderate AD from the Alzheimer’s Disease ative

Study (ADCS) Antioxidant Biomarker study, a double-blind,

randomized multicenter clinical trial.

Study subjects were randomly assigned to 1 of 3 treatments for 16

weeks: 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of

vitamin C plus 900 mg/d ALA (E/C/ALA); 400 mg of CoQ 3 times a

day; or placebo.

All treatments were well tolerated. Clinical measures of

cognitive abilities were done using the MMSE and functional

assessment using the ADCS Activities of Daily Living (ADCS-ADL)

scale.

Although MMSE scores did not differ between groups at baseline,

they showed a greater decline in the E/C/ALA group relative to

placebo over time. Trends also showed greater decline in ADCS-ADL

scores in the E/C/ALA group.

Table. 16-Week Changes in MMSE and ADCS-ADL by Group

Variable

E/C/ALA

CoQ

Placebo

MMSE score, mean

23.1

23.3

23.1

MMSE score change

−2.8

−1.0

−0.9

ADCS-ADL score, mean

61.1

65.2

65.4

ADCS-ADL score change

−4.6

−2.4

−2.3

ADCS-ADL = Alzheimer’s Disease ative Study

– Activities of Daily Living; ALA = alpha-lipoic acid; C =

vitamin C; CoQ = coenzyme Q; E = Vitamin E; MMSE = Mini-Mental

State Examination

The accelerated decline on the MMSE and a trend in this direction

on the ADCS-ADL in the E/C/ALA group hints that this combination

could adversely affect cognition in AD, the authors note.

"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 "will need to be

carefully monitored if longer-term studies are planned," they

write.

Sixty-six patients provided serial CSF specimens adequate for

biochemical analyses during the 16-week trial. The combination of

E/C/ALA did not affect CSF biomarkers related to beta-amyloid-42

(Aβ42), tau, or P-tau181, suggesting that this antioxidant

combination did not influence pathways related to amyloid and tau

pathology, the authors say.

However, E/C/ALA did result in a significant (P =.04)

decrease in CSF F2-isoprostane levels, consistent with antioxidant

effects in the brain. The decrease was 19% on average from

baseline to week 16. CSF F2-isoprostane levels were unchanged in

the other groups.

They also say the "absence of a biomarker signal" with CoQ

suggests that this antioxidant, at the tested dose, does not

improve indices of oxidative stress or neurodegeneration.

Commenting on the data, Dr. Scarmeas noted that "cognition is a

complex outcome of multiple biological mechanisms, and thus not a

direct correlate of a single biomarker (or) pathway. We probably

need to simultaneously consider multiple biomarkers (mechanisms)

in such studies and always in light of clinical outcomes," he

said.

The study was supported by the National Institute on Aging.

The authors and Dr. Scarmeas have disclosed no relevant

financial relationships.

Arch Neurol. Published online March 19, 2012. Abstract