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* A.G.E.s can be important pathologic agents responsible for the
morphologic and functional deficits of diabetic nephropathy.
* Alagebrium appears to protect kidney structure and function and
reverses A.G.E - mediated effects on the kidney.
* As early as the 3rd week of treatment, alagebrium decreases the
serum concentration of eN-carboxymethyllysine (CML), a marker of
Advanced 8Glycation End-products (A.G.E.s), by 41%, concomitant with
increasing urinary excretion of CML by 138%.
* By 3 months of treatment, alagebrium reduces serum, skin and
kidney levels of CML, while increasing their output in the urine.
* A rise in the albumin/creatinine ratio and morphological and
structural changes associated with diabetic nephropathy can be
slowed or reversed by alagebrium.

[The above was just posted to the newsgroup sci.life-extension today (9/20) and
I posted the abstract for it there, and now here below.

Am J Nephrol. 2006 Sep 13;26(5):430-436
Prevention and Reversal of Diabetic Nephropathy in db/db Mice Treated with
Alagebrium (ALT-711).
Peppa M, Brem H, Cai W, Zhang JG, Basgen J, Li Z, Vlassara H, Uribarri J.
Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Research
Institute and Diabetes Center, 'Attikon' University Hospital, Athens, Greece.

Background: Alagebrium (ALT-711) has been shown to improve renal dysfunction in
animal models of diabetes. Methods: To test its effects in diabetic nephropathy
(DN), ALT-711 was administered (1 mg/kg daily i.p.) to 9-week-old female db/db
mice (n = 15, group A1) for 3 weeks and to 3-month-old (n = 15, group A2),
7-month-old (n = 7, group A3), and 12-month-old (n = 5, group A4) female db/db
mice for 12 weeks, while a similar number of diabetic and nondiabetic mice were
used as controls. The epsilonN-carboxymethyllysine (CML) levels in serum, urine,
skin, and kidney tissue were measured by enzyme-linked immunosorbent assay. The
renal morphometric parameters were assessed by electron and light microscopy.
Results: By the 3rd week of treatment, the serum CML level decreased by 41%, and
the urinary CML concentration increased by 138% from baseline, while the urinary
albumin/creatinine ratio was lower (p < 0.05) in diabetic and nondiabetic group
A1 mice. After 3 months of treatment, serum, skin, and kidney CML levels and
urinary albumin/creatinine ratio were lower (p < 0.05) and the urinary CML
levels higher (p < 0.05) in treated group A2, A3, and A4 animals compared with
groups which received phosphate-buffered saline, with a similar pattern observed
in nondiabetic mice. The renal morphological parameters characteristic of DN
decreased in treated compared with untreated mice. Conclusion: Alagebrium may
prevent, delay, and/or reverse established DN in db/db mice by reducing the
systemic advanced glycation end product pools and facilitating the urinary
excretion of advanced glycation end products.
PMID: 16974073

--Paul]

[Interestingly as seen in figure 3 in the full text the kidney CML levels of the
diabetic group given ALT-711 were not only lower than in the untreated diabetic
group but they actually declined from 3 months of age to 7 months of age and
further to 12 months of age. -°Olafur]


Wonder if you could comment on this because I seem to remember there
was a discussion here where you (Paul) questioned whether alagebrium
was effective or breaking the right A.G.E.s (please clarify) and
whether the new data would change your perspective.

[*I* did not question it. I merely mentioned that some quite reputable
biochemical scientists had questioned it and the early evidence seemed to be in
favor of their opinion that ALT-711 did not break the AGEs and crosslinks that
were the most important in the body as a whole. However, there are many types of
crosslinks and AGEs and their importance varies considerably with different
tissue types.

There has since been good evidence that ALT-711 will break the cross links that
are most prevalent in the eye lens and that it might totally reverse presbyopia
and possibly even cataracts. The procedure to do this is not simple and I am
getting ready to try it on myself (likely not until I get back to Casa Grande at
the end of October).

You are right that this result for kidneys provides good evidence that ALT-711
will break CML AGEs (or if not actually break them, will cause them to be
dislodged and excreted) and that CML AGEs may be particularly harmful with
respect to kidney function. --Paul]


I have been considering adding alagebrium to my regimen, but am not
sure if at 40 years old it would be the right time to be doing it.
Would a younger person need less? Or is it a good all-around
preventative?

[Since ALT-711 has been used sufficiently long by sufficiently many people that
it appears to be without major negative effects in moderate dosages (less than 2
mg/kg for chronic use) and cross-links and AGEs have accumulating primary
negative effects from the day that you are born, I am now of the opinion that it
is never too early to start using it as an important preventive measure, with
the exception being that perhaps it is still wise to wait until physical
maturity. As with most supplements, a younger person will likely need less and
would be safer to take less since s/he is going to be taking it for a longer
time. So for a 25 year old in perfect health (for that age) I would suggest at
most 1/2 mg/kg daily, but for someone of age 40 1 mg/kg would not likely be too
much.

Note that while the dosage used for the mice in the experiment above was quite
low (1 mg/kg) and mouse dosages are normally reduced by a factor of about 7 to
get human dosages, the fact that it was given IP (intraperitoneal) greatly
enhances the dosage that actually reaches cells. That is why I still think human
dosages should be approximately as I have stated above. --Paul]