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Science Forum Index » Life Extension Forum » OTC anti-AGE question...
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| Jefferson... |
 Posted: Mon May 12, 2008 11:03 am |
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Olafur Pall Olafsson wrote:
Quote: I was surprised that you did not list resveratrol. There have been
studies that relate resveratrol to AGE inhibition. It may be true that
the mega doses needed might be too expensive for many people.
Frank
While resveratrol may be able to prevent some of the harmful effect of
AGEs I have not seen any study that indicates it can inhibit their
formation. I doubt such a study exists, and if it does it is most
likely an in vitro study, in which case the results would not be
applicable to humans based on the low bioavailability of resveratrol.
Since resveratrol is being used in mega doses to treat type 2 diabetics
and those with metabolic syndrome there should be in vivo evidence
available for humans to support AGE inhibition with resveratrol in the
near future. It only remains for the evidence to be released.
"Sirtris Announces Positive Results with Proprietary Version of
Resveratrol, SRT501, in a Phase 1b Type 2 Diabetes Clinical Study
January 8, 2008
SRT501, the first SIRT1 activator to enter the clinic, shows safety,
trends in lowering fasting plasma glucose, and a significant lowering of
glucose in an oral glucose tolerance test as presented at the 26th
Annual JPMorgan Healthcare Conference, January 7th 2008
CAMBRIDGE, Mass., Jan 07, 2008 -- Sirtris Pharmaceuticals, Inc. (NASDAQ:
SIRT), a biopharmaceutical company focused on discovering and developing
small molecule drugs to treat diseases of aging such as Type 2 Diabetes,
announced today that the Company's first product to enter the clinic,
SRT501, was found to be safe and well-tolerated, and was found to
significantly lower glucose in an oral glucose tolerance test conducted
as part of a 28 day Phase 1b clinical study in patients with Type 2
Diabetes. These data were presented at the 26th Annual JPMorgan
Healthcare Conference on Monday, January 7th 2008 at 1:30 pm PST in San
Francisco.
This 28-day Phase 1b study was designed to assess the safety,
tolerability and pharmacokinetics of once-daily, orally administered
doses of either 2.5 g or 5 g of SRT501 in patients with Type 2 Diabetes
who were naive to other diabetes drug treatments. Both doses of SRT501
were found to be safe and well-tolerated, and pharmacokinetics, a
measure of drug levels in the blood, were identical at days one and 28,
suggesting no drug accumulation. There were no serious adverse events
and no dose-related adverse events. Importantly, SRT501 showed a
statistically significant improvement in an oral glucose tolerance test
on day 28 at two hours and a trend towards lower fasting plasma glucose
levels.
SRT501 is also being tested in patients with Type 2 Diabetes in a Phase
1b BID (twice daily administration) study and in a Phase 2a study in
combination with metformin, the current first-line therapy for Type 2
Diabetes. SIRT1 is the founding member of the human sirtuin family of
enzymes which control the aging process. Specifically, SRT501 acts by
increasing mitochondrial activity and therefore is targeted to address
metabolic diseases, such as Type 2 Diabetes.
"This is the first time that a small molecule targeting sirtuins, the
genes which control the aging process, has shown efficacy in a disease
of aging," said Peter Elliott, Ph.D., Senior Vice President of
Development at Sirtris. "These Phase 1b study results are an important
step forward for Sirtris because they represent significant progress in
our clinical development of sirtuin therapeutics. We are very pleased to
see the safety profile observed in preclinical studies translate into a
well-tolerated drug molecule in patients, and we are very encouraged by
the glucose lowering effects measured in the oral glucose test."
Christoph Westphal, M.D., Ph.D., CEO and Vice Chair of Sirtris added,
"Effective treatment for Type 2 Diabetes, a disease of aging, is an
unmet medical need and sirtuin therapeutics may offer significant
potential. SRT501 may represent a promising treatment option for these
patients. We look forward to obtaining the results from our other Phase
1b clinical trial and the results from our Phase 2a clinical trial later
this year." http://tinyurl.com/66qaox
Sirtuins: Novel targets for metabolic disease -
http://tinyurl.com/64yjph; PMID: 18393104 "Elliott PJ, Jirousek M.
Sirtris Pharmaceuticals Inc, 200 Technology Square, Cambridge, MA 02139,
USA. Email: pelliott at (no spam) sirtrispharma.com.
Sirtuins represent a novel family of enzymes that are collectively well
situated to help regulate nutrient sensing and utilization, metabolic
rate and ultimately metabolic disease. Activation of one of these
enzymes, SIRT1, leads to enhanced activity of multiple proteins,
including peroxisome-proliferator activated receptor coactivator-1alpha
(PGC-1alpha), which helps to mediate some of the in vitro and in vivo
effects of sirtuins. As such, enhanced SIRT1 activity decreases glucose
levels, improves insulin sensitivity, increases mitochondrial number and
function, decreases adiposity, improves exercise tolerance and
potentially lowers body weight. SRT-501 is a proprietary formulation of
resveratrol with improved bioavailability. As such, SRT-501 represents
the first in a novel class of SIRT1 activators that has proven to be
safe and well-tolerated in humans. Clinical trials in type 2 diabetic
patients are currently underway.")
It is implicit if a pharmaceutical normalizes metabolism such as glucose
homostasis by lowering blood glucose, increasing insulin sensitivity,
etc., it would ultimately minimize the potential of AGE accumulation.
This is not to say AGE accumulation will not occur by having HbA1c
levels less than 4.7%.
A scholar.google search for resveratrol+"advanced glycation
end-product"+AGE+inhibitor+human resulted in 57 finds. Quite a few of
these finds have been cited frequently.
Frank |
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| David Saum... |
| Posted: Mon May 12, 2008 8:20 pm |
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"Thyro" <thyroactive1 at (no spam) gmail.com> wrote in message
news:193c7a6b-0cf7-4ee0-b31b-07fd50f5a50e at (no spam) m3g2000hsc.googlegroups.com...
Quote: Five years ago on this forum I asked:
"What's the best Anti-glycation agent available over-the-counter (if
any). "
Suggestions included:
Benfotiame
Carnosine
Chromium
Biotin
Magnesium
Aspirin (maybe)
And avoiding glycating foods and food preparation methods.
What's the thinking now? Any additions? New suggestions?
flavonoids?
----- Original Message -----
From: "Olafur Pall Olafsson" <olafurpall at (no spam) yahoo.com>
Newsgroups: sci.life-extension
Sent: Wednesday, November 07, 2007 1:47 AM
Subject: [Inhibition of advanced glycation by flavonoids. A nutritional
implication for preventing diabetes complications?]
J Soc Biol. 2007;201(2):189-98.
Click here to read
[Inhibition of advanced glycation by flavonoids. A nutritional
implication for preventing diabetes complications?]
[Article in French]
Urios P, Grigorova-Borsos AM, Peyroux J, Sternberg M.
Equipe de recherche "Protéines modifiées, protéases et
physiopathologie de l'endothélium vasculaire", Département de
Biochimie, Faculté de Médecine & Laboratoire de Pharmacologie, Faculté
de Pharmacie, Université René Descartes, Paris, France;
Advanced glycation of collagens contributes to development of
micro- and macrovascular complications in diabetes. Since flavonoids
are potent natural antioxidants, it was interesting to examine their
effect on the formation of a cross-linking advanced glycation
endproduct, pentosidine, in collagen incubated with glucose. Monomeric
flavonoids (25 and 250 microM) markedly reduced pentosidine/
hydroxyproline values in a concentration- and structure-dependent
manner. Procyanidin oligomers from grape seed were more active than
pine bark procyanidin oligomers. Oligomers are known to be cleaved
into monomers in the gastric milieu and monomeric flavonoids to be
absorbed and recovered at micromolar concentrations (with a long
plasmatic half-life) in extracellular fluids, in contact with
collagens. In conclusion, flavonoids are very potent inhibitors of
pentosidine formation in collagens, active at micromolar
concentrations; these concentrations might be achieved in plasma of
diabetic patients after oral intake of flavonoids.
Publication Types:
* English Abstract
PMID: 17978753 [PubMed - in process]
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