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DHEA supplement shows no effect on Alzheimer's disease

Ian Goddard igoddard at erols.mom
Sat Apr 12 20:55:42 EST 2003

"James Michael Howard" <jmhoward at arkansas.net> wrote:

>DHEA is known to produce "neuroprotective" effects on the brain.  In 1985, I
>copyrighted the hypothesis that low DHEA may result in AD in vulnerable
>people.  (My principal hypothesis is that DHEA evolved to optimize
>replication and transcription of DNA, so I decided that reduced DHEA should
>adversely affect neuronal tissues, tissues which I believe to be exquisitely
>sensitive to levels of DHEA.)  If one assumes that declining DHEA results in
>lack of support of neuron function, then "disease" processes may accrue.
>(Neuronal maintenance declines to the point of neuronal dysfunction.)  If
>this disease process advances to a point where normal neuron functions are
>not able to repair the damage, then the stimulus of supplemental DHEA would
>probably not increase repair.  The key to studying DHEA is a large study
>involving a large number of people taking DHEA before the average onset of
>AD pathology.  The study you cite fails in the same way gasoline fails to
>help cars which have already failed.
>> http://www.eurekalert.org/pub_releases/2003-04/aaon-dss033103.php

  IAN: A likely flaw in that study is the relatively low dose used, 
  100 mg. I've seen much higher doses in non-Alzheimer's studies. 
  The Life Extension Foundation says for DHEA, "the usual dose 
  is ... 40-100 mg in males." It seems reasonable that in extreme 
  cases such as dementia larger doses might be required. I think 
  the study should have examined much higher doses than 100 mg. 

  Note also that at three months, 100 mg produced a benefit although 
  "the benefit narrowly missed statistical significance." Mr Howard's
  DHEA-Alzheimer's hypothesis is not without indications in research 
  such as the following selections, which are just a few among many:

Brain Res Mol Brain Res  1999 Mar 20;66(1-2):35-41 

Dehydroepiandrosterone (DHEA) protects hippocampal cells from
oxidative stress-induced damage.

Bastianetto S, Ramassamy C, Poirier J, Quirion R.

Department of Psychiatry, Douglas Hospital Research Centre, McGill
University, 6875 LaSalle Boulevard, Verdun, Quebec, Canada.

It has been postulated that decreases in plasma levels of
dehydroepiandrosterone (DHEA) may contribute to the development of
some age-related disorders. Along with neuroprotective and memory
enhancing effects, DHEA has been shown to display antioxidant
properties. Moreover, oxidative stress is known to cause lipid
peroxidation and degenerative changes in the hippocampus, an area
involved in memory processes and especially afflicted in Alzheimer's
disease (AD). Accordingly, we investigated the antioxidant effects of
DHEA in models of oxidative stress using rat primary hippocampal cells
and human hippocampal tissue from AD patients and age-matched
controls. A pre-treatment of rat primary mixed hippocampal cell
cultures with DHEA (10-100 microM) protected against the toxicity
induced by H2O2 and sodium nitroprusside. Moreover, DHEA (10-100
microM) was also able to prevent H2O2/FeSO4-stimulated lipid oxidation
in both control and AD hippocampal tissues. Taken together, these data
suggest that DHEA may be useful in treating age-related central
nervous system diseases based on its protective effects in the
hippocampus. Copyright 1999 Elsevier Science B.V.

PMID: 10095075 [PubMed - indexed for MEDLINE]


Neuropsychobiology  2000;42(2):51-7 

Hippocampal perfusion and pituitary-adrenal axis in Alzheimer's

Murialdo G, Nobili F, Rollero A, Gianelli MV, Copello F, Rodriguez G,
Polleri A.

Department of Endocrinological and Metabolic Sciences, Epidemiology
Service, University of Genova, Italy. disem at unige.it

The hippocampus is involved in Alzheimer's disease (AD) and regulates
the hypothalamus-pituitary-adrenal axis (HPAA). Enhanced cortisol
secretion has been reported in AD. Increased cortisol levels affect
hippocampal neuron survival and potentiate beta-amyloid toxicity.
Conversely, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are
believed to antagonize noxious glucocorticoid effects and exert a
neuroprotective activity. The present study was aimed at investigating
possible correlations between hippocampus perfusion - evaluated by
SPECT - and HPAA function in AD. Fourteen patients with AD and 12
healthy age-matched controls were studied by (99m)Tc-HMPAO
high-resolution brain SPECT. Plasma adrenocorticotropin, cortisol, and
DHEAS levels were determined at 2.00, 8.00, 14.00, 20.00 h in all
subjects and their mean values were computed. Cortisol/DHEAS ratios
(C/Dr) were also calculated. Bilateral impairment of SPECT hippocampal
perfusion was observed in AD patients as compared to controls. Mean
cortisol levels were significantly increased and DHEAS titers were
lowered in patients with AD, as compared with controls. C/Dr was also
significantly higher in patients. Using a stepwise procedure for
dependent SPECT variables, the variance of hippocampal perfusional
data was accounted for by mean basal DHEAS levels. Moreover,
hippocampal SPECT data correlated directly with mean DHEAS levels, and
inversely with C/Dr. These data show a relationship between
hippocampal perfusion and HPAA function in AD. Decreased DHEAS, rather
than enhanced cortisol levels, appears to be correlated with changes
of hippocampal perfusion in dementia. Copyright 2000 S. Karger AG,

Publication Types:
    Clinical Trial

PMID: 10940758 [PubMed - indexed for MEDLINE]



  "To lengthen thy life, lessen thy meals." Benjamin Franklin   

  Ongoing CR monkey study update: "In the monkeys...those on
  reduced feeding since the study started are dying at a rate 
  that is about half that of the monkeys receiving a full food
  ration." Associated Press: Eating less may extend human life.
  August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-

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