LONGECITY

Hi all
just heard that research given at the American Aging Association - 34th Annual Meeting
research paper was discussed that showed alt 711 - which i presently take 50 mg a day of as do a number of you folks i know- effects/breaks only a tiny percent of primary cross-linking. i am not a bio chemist but point put forth was that the liver toxicity-
[which we were aware of as last test showed possibility of liver cancer in mice- human tests were halted]
that the liver toxicity vis a vis the small percent of crosslinking bonds actually effected by alt711 made it of questionable value. to clarify- if you took more this would not be addressed, the type of crosslinking effected by any amount is very tiny amount of crosslinking that occurs.

hope i comunicated that reasonably, the liver toxicity also appears higher than the company's tests showed according to the research. so having said this is from a knowledeable person at GeroNova who sponsered the meeting- i do not see how to get copies of that paper at
http://www.americanaging.org/2005.html so second hand info on my part but perhaps someone here was there and can fill us in?? or is a biochemist who is aware of this- i had heard whiffs of this previously but the potential - breaking exisiting crosslinking is exciting as hell and i covered my rear with mucho liver protective stuff - but if the percent is very tiny and toxicity may be higher - not worth it.
looking forward from hearing from anyone at conference or who has heard this latest research.
Chandra

Hi all
just heard that research given at the American Aging Association - 34th Annual Meeting
research paper was discussed that showed alt 711 - which i presently take 50 mg a day of as do a number of you folks i know-

Where do you get your ALT-711? If from china I would highly recommend against it.

effects/breaks only a tiny percent of primary cross-linking.

The weight of research on human and animals studies show a significant reversal of Age induced Glycation. I would not characterize its effects as “tiny”.

i am not a bio chemist but point put forth was that the liver toxicity-
[which we were aware of as last test showed possibility of liver cancer in mice- human tests were halted] that the liver toxicity vis a vis the small percent of crosslinking bonds actually effected by alt711 made it of questionable value. to clarify- if you took more this would not be addressed, the type of crosslinking effected by any amount is very tiny amount of crosslinking that occurs.

I’ve been taking ALT-711 for over 5 years….so far zero liver problems. But a few improvements on my blood tests results.

As far as the recent study (I have yet to see it) unless enough studies are done to counteract the large amount of studies showing it safe and effective.

Examples:

J Card Fail. 2005 Apr;11(3):191-5.
The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure.
CONCLUSION: Sixteen weeks of treatment with the glucose crosslink breaker, alagebrium, resulted in a decrease in left ventricular mass and improvements in left ventricular diastolic filling and quality of life in patient with DHF.

Am J Hypertens. 2004 Dec;17(12 Pt 2):23S-30S.
Advanced glycation end-product cross-link breakers: a novel approach to cardiovascular pathologies related to the aging process.

Advanced glycation end product (AGE) formation that occurs with aging and diabetes leads to the cross-linking of proteins and subsequent changes in the physicochemical properties of tissues. Cellular responses to AGE that lead to either pathological conditions or removal of AGE are mediated by a number of receptors that have been identified on various cell types such as macrophages, endothelial cells, and smooth-muscle cells. Mechanisms by which AGE affect the cardiovascular system include AGE cross-linking of long-lived proteins such as collagen and elastin and altered cellular responses. Alagebrium (3-phenacyl-4,5-dimethylthiazolium chloride, ALT-711) is the first drug in a new class of thiazolium therapeutic agents that break established AGE cross-links between proteins. In animal studies, alagebrium was effective in reducing large artery stiffness, slowing pulse-wave velocity, enhancing cardiac output, and improving left ventricular diastolic distensibility. In human studies to determine safety and efficacy, alagebrium was safe and well tolerated. In the first phase 2 clinical study, alagebrium improved arterial compliance in elderly patients with vascular stiffening. In two subsequent phase 2 clinical studies, one addressing diastolic heart failure and the other addressing systolic hypertension, alagebrium was effective in improving cardiac function and uncontrolled systolic blood pressure, particularly in more severely affected patients. Additional clinical studies to determine the utility of alagebrium in treating cardiovascular disorders associated with aging are in progress.

Diabetes. 2004 Jul;53(7):1813-23.
Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. “A sixfold increase in plaque area with diabetes was attenuated by 30% with ALT-711…”

Circulation. 2001 Sep 25;104(13):1464-70.
Improved arterial compliance by a novel advanced glycation end-product crosslink breaker.
CONCLUSIONS: ALT-711 improves total arterial compliance in aged humans with vascular stiffening, and it may provide a novel therapeutic approach for this abnormality, which occurs with aging, diabetes, and isolated systolic hypertension.

HI, could you tell me where I can buy ALT 711 ?
Edited by LifeMirage, 06 July 2005 - 07:28 AM.

Until it is approved by the FDA or another country there is no source for it that I would recommend.

has AVON (who licensed Alt-711 from Alteon) introduced a cosmoceutical using the compound yet?

Hi MethuselahMouse,

Alteon has patents on numerous related compounds (Patent No. 6,596,744)

Avon licensed a compound related to ALT-711, not ALT-711 itself.
The chemical name of the compound that Avon obtained a license to use:

2-amino-4,5-dimethylthiazole HBr

ALT-711 has a few names:

(most recent generic name) Alagebrium Chloride,

chemical names:

Phenacyldimethylthiazolium chloride or 4,5-dimethyl-3(2-oxo-phenylethyl)-thiazolium chloride

Yes, Avon seems to have incorporated the 2-amino-4,5-dimethylthiazole HBr into some of their products. A search of Avon products revealed the compound in the ingredient list of:

ANEW ALTERNATIVE Intensive Age Treatment

There may be other Avon products containing the ingredient.

I have wondered why Avon chose to license this particular one. It is a small molecule, perhaps it penetrates the skin tissue better.

Also, Alteon may have licensed the separate compound to keep regulatory issues separate (cosmetic vs drug)

Um, these guys don't ship to outside USA. Anyone got an idea where to buy the AVON cream? (i'd like to try it). amazon simple is a reseller so won't ship to europe either :-(

Ok, could someone give an overview on the efficacy vs. safety of alagebrium? At this point of trials, do you think it would be worth to take it (if you could get it), especially since I am still in my 20s? What about other AGE breakers?

I wouldn't touch that stuff with a ten foot pole. From Alteon's own research, it is hardly effective at breaking AGE whatsoever.

Hi MethuselahMouse,

Alteon has patents on numerous related compounds (Patent No. 6,596,744)

Avon licensed a compound related to ALT-711, not ALT-711 itself. 
The chemical name of the compound that Avon obtained a license to use:

2-amino-4,5-dimethylthiazole HBr

ALT-711 has a few names:

(most recent generic name) Alagebrium Chloride,

chemical names:

Phenacyldimethylthiazolium chloride or 4,5-dimethyl-3(2-oxo-phenylethyl)-thiazolium chloride

Yes, Avon seems to have incorporated the 2-amino-4,5-dimethylthiazole HBr into some of their products.  A search of Avon products revealed the compound in the ingredient list of:

ANEW ALTERNATIVE Intensive Age Treatment

There may be other Avon products containing the ingredient.

I have wondered why Avon chose to license this particular one.  It is a small molecule, perhaps it penetrates the skin tissue better.

Also, Alteon may have licensed the separate compound to keep regulatory issues separate (cosmetic vs drug)

Hey Mike. Surprised to see you in the nootropic forum!

What data have you seen that suggests ALT-711 is an "effective" AGE breaker? I've seen little compelling data. Rather, it seems Alteon's drug works at breaking AGE, but hardly. I could be mistaken.

What data have you seen that suggests ALT-711 is an "effective" AGE breaker?

The nature paper (1996) on Alt-711's precursor PTB shows this rather convincingly, but only for one type of crosslink (diketones). The problem with this is that the crosslink they break has not been isolated from living creatures, although it does form in vitro when amino acids are exposed to glucose and thus plausibly should exist in vivo (where amino acids are exposed to glucose all the time). It is possible that current methods of crosslink isolation are limiting, but it is equally possible that the clinical effects of Alt-711 are to be attributed to something else. To understand Alt-711, we need to know whether and in what abundance diketone crosslinks exist in vivo.

We will see truly impressive clinical results only with breakers that affect the highly abundant glucosepane and K2P crosslinks.

The nature paper (1996) on Alt-711's precursor PTB shows this rather convincingly, but only for one type of crosslink (diketones). The problem with this is that the crosslink they break has not been isolated from living creatures, although it does form in vitro when amino acids are exposed to glucose and thus plausibly should exist in vivo (where amino acids are exposed to glucose all the time). It is possible that current methods of crosslink isolation are limiting, but it is equally possible that the clinical effects of Alt-711 are to be attributed to something else. To understand Alt-711, we need to know whether and in what abundance diketone crosslinks exist in vivo.

We will see truly impressive clinical results only with breakers that affect the highly abundant glucosepane and K2P crosslinks.

I am not saying ALT 711 doesn't work; just that it isn't quite what Alteon hoped for.

yes , I agreed with nootropikamil, alt 711 is not so effective as what Alteon hoped for, in my research , the analogue of alt 711 has slightly reproduction toxicity

they're currently working on a glucosepene crosslink breaker, when that comes out it'll affect 40%+ of crosslinks [lol]

they're currently working on a glucosepene crosslink breaker

Do you have any further information regarding this? Please send me everything you know!

As far as the recent study (I have yet to see it) unless enough studies are done to counteract the large amount of studies showing it safe and effective.

Examples:

J Card Fail. 2005 Apr;11(3):191-5.
The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure.
CONCLUSION: Sixteen weeks of treatment with the glucose crosslink breaker, alagebrium, resulted in a decrease in left ventricular mass and improvements in left ventricular diastolic filling and quality of life in patient with DHF.

Am J Hypertens. 2004 Dec;17(12 Pt 2):23S-30S.
Advanced glycation end-product cross-link breakers: a novel approach to cardiovascular pathologies related to the aging process.

Advanced glycation end product (AGE) formation that occurs with aging and diabetes leads to the cross-linking of proteins and subsequent changes in the physicochemical properties of tissues. Cellular responses to AGE that lead to either pathological conditions or removal of AGE are mediated by a number of receptors that have been identified on various cell types such as macrophages, endothelial cells, and smooth-muscle cells. Mechanisms by which AGE affect the cardiovascular system include AGE cross-linking of long-lived proteins such as collagen and elastin and altered cellular responses. Alagebrium (3-phenacyl-4,5-dimethylthiazolium chloride, ALT-711) is the first drug in a new class of thiazolium therapeutic agents that break established AGE cross-links between proteins. In animal studies, alagebrium was effective in reducing large artery stiffness, slowing pulse-wave velocity, enhancing cardiac output, and improving left ventricular diastolic distensibility. In human studies to determine safety and efficacy, alagebrium was safe and well tolerated. In the first phase 2 clinical study, alagebrium improved arterial compliance in elderly patients with vascular stiffening. In two subsequent phase 2 clinical studies, one addressing diastolic heart failure and the other addressing systolic hypertension, alagebrium was effective in improving cardiac function and uncontrolled systolic blood pressure, particularly in more severely affected patients. Additional clinical studies to determine the utility of alagebrium in treating cardiovascular disorders associated with aging are in progress.

Diabetes. 2004 Jul;53(7):1813-23.
Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. “A sixfold increase in plaque area with diabetes was attenuated by 30% with ALT-711…”

Wow nice research. I just bought some from www.morelife.org.

How safe is that stuff?