• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

Resv and Brain Plaque


  • Please log in to reply
4 replies to this topic

#1 Shay

  • Guest
  • 54 posts
  • 6

Posted 03 June 2009 - 06:50 PM


I wonder what "clinically feasible dosages" they used? I'm no expert on the brain, but these seem like highly significant results.

The positive comment about lower glutathione in the brain is confusing because reading about the substance online suggests to me that lower glutathione is a sign of liver trouble.


======================================


Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease.
Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE. Department of Neurology and Neurosciences, Weill Medical College of Cornell University, Burke Medical Research Institute, 785 Mamaroneck Ave., White Plains, NY 10605, United States.

Resveratrol, a polyphenol found in red wine, peanuts, soy beans, and pomegranates, possesses a wide range of biological effects. Since resveratrol's properties seem ideal for treating neurodegenerative diseases, its ability to diminish amyloid plaques was tested. Mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The largest reductions in the percent area occupied by plaques were observed in medial cortex (-48%), striatum (-89%) and hypothalamus (-90%). The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%. The increased cysteine and decreased glutathione may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against beta-amyloid plaque formation and oxidative stress. PMID: 19041676 [PubMed - indexed for MEDLINE]

Edited by Shay, 03 June 2009 - 07:01 PM.


#2 VespeneGas

  • Guest
  • 600 posts
  • 34
  • Location:Oregon, atm

Posted 03 June 2009 - 08:39 PM

I would love to hear some speculation as to WHY lower GSH and higher cysteine levels would spell less cerebral plaque. Also, I second the curiosity about dosage. Anyone have access to the full text?

Click HERE to rent this advertising spot to support LongeCity (this will replace the google ad above).

#3 maxwatt

  • Guest, Moderator LeadNavigator
  • 4,949 posts
  • 1,625
  • Location:New York

Posted 03 June 2009 - 09:19 PM

I do not have the full text, but I did find this on the web:

From the article:

"The control group received a standard AIN-93G diet (Harlan Teklad,
Madison, WI) ad libitum, and the resveratrol group received standard
AIN-93G plus 0.2% resveratrol (Harlan Teklad, Madison, WI) ad libitum
for 45 days. The calculated daily dosage in mice was 300 mg/kg (3 gm
food per day for a 20 gm mouse). The human equivalent using a scaling
factor of 0.08 (http://www.fda.gov/cber/gdlns/dose.htm) is 24 mg/kg or
about 1.68 gms per day for a 70 kg individual.
"


However, Olafur wrote on Usenet sci.life-extension:

the scaling factor FDA gives above is incorrect. A more correct scaling factor can
be gotten using the quarter power scaling law in which case the
scaling factor between a 20g mouse and a 10kg human would be:
((70000/20)^(3/4)) / (70000/20) = 0,13 . The dose for a 70kg human would then be 300mg/kg x 70kg x 0,13 = 2,73g
of resveratrol daily.


Edited by maxwatt, 03 June 2009 - 09:39 PM.


#4 niner

  • Guest
  • 16,276 posts
  • 2,000
  • Location:Philadelphia

Posted 03 June 2009 - 10:28 PM

I also don't have access to the text. cough (Elsevier is a boil on the ass of science....) cough. The scaling laws described here are meant for safety studies, not dose translation for eliciting a pharmacological effect. Based on blood levels achieved in rodents vs men for a given oral dose of resveratrol, I would expect the true translation to be toward or beyond the higher end of the estimates here. However, this was not a dose-ranging study. The guys doing this experiment wanted to be sure they saw an effect, so they probably used more resveratrol than was really needed. It is difficult to extrapolate from this one abstract what dose of resveratrol would be protective against resveratrol. After all, it's only a mouse model of the disease anyway. The possible use of resveratrol in AD was reviewed a few years ago. I'm sure that a lot has happened since.

Brain Res Rev. 2006 Sep;52(2):316-26.
Resveratrol--a boon for treating Alzheimer's disease?
Anekonda TS.

Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, 97006, USA. anekondt@ohsu.edu

Resveratrol, a red wine polyphenol, is known to protect against cardiovascular diseases and cancers, as well as to promote antiaging effects in numerous organisms. It also modulates pathomechanisms of debilitating neurological disorders, such as strokes, ischemia, and Huntington's disease. The role of resveratrol in Alzheimer's disease is still unclear, although some recent studies on red wine bioactive compounds suggest that resveratrol modulates multiple mechanisms of Alzheimer's disease pathology. Emerging literature indicates that mechanisms of aging and Alzheimer's disease are intricately linked and that these mechanisms can be modulated by both calorie restriction regimens and calorie restriction mimetics, the prime mediator of which is the SIRT1 protein, a human homologue of yeast silent information regulator (Sir)-2, and a member of NAD+-dependent histone deacetylases. Calorie restriction regimens and calorie restriction-mimetics trigger sirtuins in a wide variety of organisms, ranging from bacteria to mouse. In a mouse model of Huntington's disease, resveratrol-induced SIRT1 was found to protect neurons against ployQ toxicity and in Wallerian degeneration slow mice, resveratrol was found to protect the degeneration of neurons from axotomy, suggesting that resveratrol may possess therapeutic value to neuronal degeneration. This paper mainly focuses on the role of resveratrol in modulating AD pathomechanisms.

PMID: 16766037



Click HERE to rent this advertising spot to support LongeCity (this will replace the google ad above).

#5 Dmitri

  • Guest
  • 841 posts
  • 33
  • Location:Houston and Chicago

Posted 04 June 2009 - 08:14 AM

I would love to hear some speculation as to WHY lower GSH and higher cysteine levels would spell less cerebral plaque. Also, I second the curiosity about dosage. Anyone have access to the full text?


Here's the article (I hope the link works, I was able to open it with my university code):

EDIT: I deleted the cookies and tried logging on using the link but it doesn't seem to work without my code, so I guess I'll have to read it later and post the information you wanted.

Edited by Dmitri, 04 June 2009 - 08:22 AM.





1 user(s) are reading this topic

0 members, 1 guests, 0 anonymous users