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Welcome to the Quality Counts. For those health conscious consumers and medical professionals that are looking to purchase nutritional supplements, vitamins, herbs, learning about medications, losing weight, health food, low carbs, high protein nutrition, and exercise, you have come to the right place. Quality Counts serves both the medical practitioner and consumer interested in nutritional therapy and alternative medicine.
Home > Anti-aging Research > AGEs.
Advanced Glycation End Product (AGE) inhibitors & ALT-711 (dimethyl-3-phenacylthiazolium chloride)
Specific Recommendations:
- carnosine / alpha lipoic acid / acetyl-l-carnitine / ginseng / gymnema / chromium / Metformin /
l-arginine
- If you do a search of "Aminoguanidine pimagedine", several sites claim they are the same thing. Aminoguanidine is available at International Anti-aging Systems
General Information:
-
Advanced glycation endproduct
-
Wikipedia - "AGEs affect nearly every type of
cell and molecule in the body, are thought to be major factors in aging and
age related chronic diseases. They are also believed to play a causative
role in the vascular complications of diabetes mellitus"
-
Glucose, Advanced Glycation End Products, and Diabetes Complications: What
Is New and What Works - Clinical Diabetes 21:186-187, 2003 -
"A large body of evidence suggests that AGEs are
important pathogenetic mediators of almost all diabetes complications,
conventionally grouped into micro- or macroangiopathies"
- Cross-link Breakers and Inhibitors - International Anti-Aging Systems
- "It is now well established that the process of
glycosylation is one of the most important causes of ageing, perhaps equally
as important as the process of oxidation (free radical damage)"
- Books on Advanced Glycation End Products - Amazon.com
News & Research:
-
Advanced glycation end products and diabetic foot disease - Diabetes
Metab Res Rev. 2008 May-Jun;24 Suppl 1:S19-24 -
"recent clinical studies have shown that the AGE-breakers may be able to
decrease adverse vascular effects of glycation with few side effects"
-
Advanced glycation end products in senile diabetic and nondiabetic patients
with cataract - J Diabetes Complications. 2008 May 26 -
"The AGE distribution in the senile groups
corroborates the hypothesis that the advanced glycation process might have a
role in cataract formation, which in diabetic patients occurs vigorously as
compared with nondiabetic cataract patients"
-
When
It Comes To Living Longer, It's Better To Go Hungry Than Go Running, Mouse
Study Suggests - Science Daily, 5/14/08 - "at
least two studies which examined people who engage in high-volume exercise
versus people who restricted their calorie intake, had a similar outcome:
caloric restriction has physiological benefits that exercise alone does not
... One theory is that exercise places stress on the body, which can result
in damage to the tissues and DNA. Another theory is that caloric restriction
leads to physiological changes which benefit the body" - I still
think it boils down to the ravages of higher insulin and blood sugar which
increase advanced glycation end products a major cause of aging.
-
Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced
Glycation End-product (AGE)-elicited Hepatic Insulin Resistance via
Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med
Res. 2008 Mar-Apr;36(2):237-43 - "Candesartan,
another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at
serine-307 residues in Hep3B cells. Our study suggests that telmisartan
could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting
serine phosphorylation of IRS-1, at least in part, via activation of
PPAR-gamma" - Note: That might be another reason for
considering telmisartan as a
first line treatment for
hypertension. See telmisartan at
OffshoreRX.com
 .
-
Effect of Rosiglitazone on Cardiac Fibroblast Proliferation, Nitric Oxide
Production and Connective Tissue Growth Factor Expression Induced by
Advanced Glycation End-products - J Int Med Res. 2008
Mar-Apr;36(2):329-35 - "AGEs significantly
accelerated proliferation, increased CTGF expression and decreased nitric
oxide production in cardiac fibroblasts. These effects of AGEs were
inhibited by RGZ in a dose-dependent manner"
-
Increased serum Advanced Glycation End products is a distinct finding in
lean women with PCOS - Clin Endocrinol (Oxf). 2008 Mar 20 -
"PCOS women exhibited statistically higher AGEs
levels"
-
How
Diabetes Drives Atherosclerosis - WebMD, 3/13/08 -
"Abe's team showed that molecules called advanced
glycation end products (AGEs), produced in greater levels by patients with
diabetes, interfere with ERK5 cardioprotection. Glycation reactions cause
the release of oxidizing side products like hydrogen peroxide (H202) that
drive free radical production, inflammation and cell damage in many diseases"
- I was always under the impression that it was advanced glycation
end products in the first place. I guess I was right before they
discovered it.
-
DHEA
Restores Oxidative Balance in Type 2 Diabetes - Medscape, 12/11/07 -
"DHEA significantly reduced oxidative stress
parameters in both plasma and peripheral blood mononuclear cells, the report
indicates, and its administration was followed by a 50% decrease in levels
of pentosidine (a marker of AGE formation)" - See
DHEA products at iHerb
 .
-
Face
facts: Too much sugar causes wrinkles - MSNBC, 10/21/07 -
"At blame is a natural process that's known as
glycation, in which the sugar in your bloodstream attaches to proteins to
form harmful new molecules called advanced glycation end products (or,
appropriately, AGEs for short). The more sugar you eat, the more AGEs you
develop. "As AGEs accumulate, they damage adjacent proteins in a domino-like
fashion," ... Supplement your diet with at least 1 mg of vitamins B1 and B6
a day. These vitamins proved to be potent AGE inhibitors in a number of
published studies"
-
Dehydroepiandrosterone administration counteracts oxidative imbalance and
AGE formation in type 2 diabetic patients - Diabetes Care. 2007 Aug 17 -
"Data indicate that DHEA treatment ameliorates the
oxidative imbalance induced by hyperglycaemia, down-regulates the TNFalpha/TNFalpha
receptors system and prevents AGE formation, suggesting a beneficial effect
on the onset and/or progression of chronic complications in type 2 diabetic
patients"
-
Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced
Glycation End-product (AGE)-induced Monocyte Chemoattractant Protein-1
Expression in Mesangial Cells Through Downregulation of Receptor for AGEs
via Peroxisome Proliferator-activated Receptor-gamma Activation - J Int
Med Res. 2007 Jul-Aug;35(4):482-9 - "Candesartan, an
Ang II type 1 receptor blocker, did not suppress AGEs-induced superoxide
generation. Telmisartan and the antioxidant, N-acetylcysteine, completely
inhibited AGEs-induced MCP-1 overproduction by mesangial cells"
-
Protective Effect of (-)-Epigallocatechin Gallate against Advanced Glycation
Endproducts-Induced Injury in Neuronal Cells - Biol Pharm Bull. 2007
Aug;30(8):1369-73 - "Advanced glycation endproducts
(AGEs) are believed to be secondary factors in the selective neuronal injury
associated with several neurodegenerative disorders. In this study, we
investigated the protective effects of (-)-epigallocatechin gallate (EGCG),
a major monomer of green tea polyphenols, against AGEs-induced damage in
neuron cells. The results showed that EGCG treatment protected against
glyceraldehyde-derived AGE-induced neurotoxicity" - See
green tea products at iHerb.
-
Thiazolidinedione increases serum soluble receptor for advanced glycation
end-products in type 2 diabetes - Diabetologia. 2007 Jul 18 -
"At 6 months, both rosiglitazone and sulfonylurea
resulted in a significant reduction in HbA(1c), fasting glucose and AGE"
-
Cooking to Fight
Inflammation? - Dr. Weil, 7/12/07 - "You can
reduce your intake of AGEs by steaming or boiling foods or by making stews –
the key is to cook at low heat and to maintain the water content of food"
-
Advanced glycation endproducts: what is their relevance to diabetic
complications? - Diabetes Obes Metab. 2007 May;9(3):233-45 -
"AGEs may potentiate the development
of diabetic complications by activation of cell responses by AGE-modified
proteins interacting with specific cell surface receptors, activation of
cell responses by AGE free adducts, impairment of protein-protein and
enzyme-substrate interactions by AGE residue formation, and increasing
resistance to proteolysis of extracellular matrix proteins. The formation of
AGEs is suppressed by intensive glycaemic control, and may in future be
suppressed by thiamine and pyridoxamine supplementation, and several other
pharmacological agents"
-
Advanced glycation end-products and arterial stiffness in hypertension -
Am J Hypertens. 2007 Mar;20(3):242-7 - "Concentration of plasma AGEs is
significantly higher in hypertensive than in normotensive subjects and
related to aortic stiffness independent of age and blood pressure"
-
Benfotiamine prevents macro- and microvascular endothelial dysfunction and
oxidative stress following a meal rich in advanced glycation end products in
individuals with type 2 diabetes - Diabetes Care. 2006 Sep;29(9):2064-71
- "Our study confirms micro- and
macrovascular endothelial dysfunction accompanied by increased oxidative
stress following a real-life, heat-processed, AGE-rich meal in individuals
with type 2 diabetes and suggests benfotiamine as a potential treatment"
-
Effect of valsartan, an angiotensin II receptor blocker, on markers of
oxidation and glycation in Japanese type 2 diabetic subjects: Blood
pressure-independent effect of valsartan - Diabetes Res Clin Pract. 2006
May 29 - "low-dose valsartan
treatment decreased serum AGEs level, whereas blood pressure level was
unchanged. The effect of valsartan on AGEs might be a blood
pressure-independent effect in type 2 diabetic subjects"
-
Antiglycation properties of aged garlic extract: possible role in prevention
of diabetic complications - J Nutr. 2006 Mar;136(3):796S-9S -
"S-Allylcysteine, a key component of
aged garlic, is a potent antioxidant and can inhibit AGEP formation"
- Phase
II Data Show Alagebrium Reduces Arterial Stiffness in Elderly With Isolated
Systolic Hypertension - Medscape, 11/23/05
-
Drug
Compound Restores Youth To Aging Arterial Cells In Elderly Hypertensives,
Hopkins Study Shows - Science Daily, 11/23/05 -
"alagebrium, formally known as
ALT-711 or 4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium chloride, reduced
stiffening in the vessel wall in the main artery of the neck (carotid
artery) by as much as 37 percent. The drug also improved endothelial
function, the ability of the vessels' inner lining to relax and dilate in
response to increased stress from blood flow, by 102 percent"
-
Simvastatin's Benefits May Extend to Atherosclerotic Plaque Stabilisation in Diabetics - Doctor's Guide, 10/25/04 -
"Simvastatin-dependent
plaque stabilisation in patients with type 2 diabetes arises from the drug's ability to decrease expression of receptor for advanced glycation end products (RAGE), and thence to reduce metalloproteinase (MMP)
activity, and promote plaque stabilisation"
- New Class of Antihypertensive Agents Continues in Development - Medscape, 8/19/03 -
"ALT-711 did not demonstrate statistical significance compared with placebo against the
prespecified primary endpoint of reduction of SBP by office cuff pressure measurement at the highest of 4
dose levels (210 mg/day)"
-
Eating
Food Cooked At High Temperature Accelerates Aging - Life Extension Magazine, 5/03 -
"consuming foods high in glycotoxins might be responsible for the induction of a low-grade, but chronic state of inflammation. In addition, the glycotoxins in food cooked at high
temperatures also promote the formation of glycotoxins in our living tissues. The implication of these findings is profound ... Inflammatory cytokine production can be suppressed with the proper supplementation of fish oil, DHEA, vitamin K and nettle leaf extract ... It is also important to avoid over consumption of
foods high in arachidonic acid (beef, egg yolk, dairy, etc.) ... Consuming at least 1000 mg a day of carnosine, and/or 300 mg of the European drug aminoguanidine can inhibit pathological
glycation reactions in the body" - See
iHerb
 or Vitacost
carnosine products.
- Ramipril Reduces Advanced Glycation End Products In Non-Diabetic Nephropathy - Doctor's Guide, 4/21/03 -
"Ramipril
also mildly decreased levels of advanced glycation end products"
- Vitamin C May Aid People with Diabetes - New Hope Natural Media, 2/13/03 -
"Vitamin C inhibits all three of the biochemical reactions that are believed to contribute to the
development of these complications: (1) the production of oxygen-derived free radicals, (2) the accumulation of sorbitol within cells, and (3) a tissue-damaging reaction called glycosylation" - [J.
Hypertension/Medline]- See
iHerb or
Vitacost
vitamin C products.
-
Preserving
Clear Vision - Life Extension Magazine, 2/03 - "It is likely that glycation plays a role in aging in non-diabetics as well, especially those who eat diets high in sugars and refined carbohydrates or those who have blood
sugars higher than normal but not high enough to merit a diabetes diagnosis ...
Carnosine's best-known effect, however, is its ability to prevent the formation of advanced glycated end
products (protein crosslinks). Carnosine competes with proteins for the binding sites they would occupy on sugar molecules, making it the best glycation preventative currently recognized in the world of nutrition research"
- See
iHerb or Vitacost
carnosine products.
-
The
Anti-Aging Effects of Carnosine - Life Extension Magazine, 1/03 -
"Carnosine quenches the most destructive protein-oxidizing agent (the hydroxyl radical). One study showed carnosine was the only antioxidant to significantly protect cellular
chromosomes from oxidative damage.2 Antioxidants cannot completely protect proteins. Nature's second line of defense is to repair or remove damaged proteins.3 This is where carnosine demonstrates its most profound anti-aging effect ... Studies show that carnosine is effective against cross-linking and the formation
of advanced glycation end products (AGE).6,7 Glycated proteins produce 50-fold more free radicals than nonglycated proteins and carnosine may be the most effective anti-glycating agent known" - See
iHerb or Vitacost
carnosine products.
- High-Heat Foods Could Be Bad For You - CBS News, 11/28/02 -
"browned, crispy foods, like that Thanksgiving turkey you just ate, are loaded with proteins
called AGEs which interact with sugar in the body to cause hardening of the arteries ... AGEs are deposited everywhere over time
— in the kidneys, in the vessels of the eyes and they have been implicated in all of these major complications from diabetes"
- Diabetic Heart Disease Risk Studied - Intelihealth, 11/12/02
- Three Of 12 Patients Taking Pyridorin (Pyridoxamine Dihydrochloride) Convert From Macro- To Microalbuminuria - Doctor's Guide, 11/3/02 -
"all
dose levels of Pyridorin were well tolerated, with no serious adverse events reported and no discontinuations due to an adverse event ... Patients taking Pyridorin experienced an average decrease from baseline 24-hour urinary albumin excretion of 32 percent at day 45" - Sounds
like Pyridorin by
BioStratum is a competitor to pimagedine by Alteon. Pyridorin and pimagedine are advanced glycation end product (AGE) inhibitors
Alteon is also working on ALT-711, which is an advanced glycation end
product (AGE) reverser. Carnosine and acetyl-l-carnitine are supplements believed to be advanced glycation end product (AGE) inhibitors. - Ben
-
Why
Antioxidants Aren't Enough - Life Extension Magazine, 1/02
- Oxidative Marker Found In Rheumatoid Arthritis Synovial Tissue - Doctor's Guide, 6/12/02 -
"Raised
AGE levels have been found in the serum and synovial fluid of patients with RA"
- Glycation Levels Could Affect Progression Of Osteoarthritis - Doctor's Guide, 12/7/01
-
What
constitutes a glycation-reduced diet? - Life Extension Magazine, 11/01 -
"Glycation of proteins has been shown to play a prominent role in the development of many diseases related to diabetes, atherosclerosis and cataract formation. Glycation also occurs as a result of
general aging. A glycation reduction diet would be one that is low in simple sugars and carbohydrates. There are also certain supplements that help reduce glycation, such as carnosine. Carnosine is the most effective natural anti-glycating agent ... Other supplements include
alpha lipoic acid, chromium picolinate and calcium pyruvate"
- Alteon's ALT-711 Found to 'Remodel' Cardiovascular System in Preclinical Study - Alteon, 9/24/01 -
"released results of a new
preclinical study that demonstrated the ability of ALT-711 to decrease the thickening of the heart that may occur as a result of hypertension, and to improve the function of the endothelium ... ALT-711 normalized left ventricular fibrosis, or the thickening of the left ventrical of the heart, and improved the
function of the endothelium, the part of the cardiovascular system that regulates both the relaxation and contraction of blood vessels and contributes to the maintenance of the vascular structure. The authors suggest that ALT-711 may be effective for improving cardiovascular remodeling in hypertension"
-
AGE
Breakers - Life Extension Magazine, 8/01 - "If ALT-711 is ever approved by the FDA, it will enable aging humans to reverse the effects of glycation, one of the most devastating consequences of aging"
- Experimental Drug Decreases Age-Related Blood Vessel Stiffening - Doctor's Guide, 9/5/01 -
"In a group of older people with vascular stiffening, the drug, ALT-711, significantly reduced
arterial pulse pressure, defined as the difference between systolic blood pressure and diastolic blood pressure. It also improved the blood vessels' ability to stretch by about 14 percent"
- Aminoguanidine: AGE Inhibitor - Phil Micans PharmB/IAS -
"the membrane surface area of the rats was reduced by 30%. Furthermore, the collagen content of their arterial walls was increased by 24-30%.
Aminoguanidine is therefore acting to improve overall heart and arterial condition and not just by preventing or slowing proteins from cross-linking, but also by decreasing the AGE-induced cross-linking of the extra-cellular matrix ... 11 patients with peripheral vascular disease were treated with aminoguanidine.
Their blood vessels were so clogged that they couldn't walk for more than 500 yards. But after treatment with aminoguanadine the patients blood flow improved on average by 30% and the patients exercise abilities improved by 50% to 105%."
- Alteon Initiates Phase IIb 'SAPPHIRE' Trial of ALT-711 in Systolic Hypertension - Alteon, 7/9/01 -
"By "breaking" the
pathological bonds that cause tissues, organs and vessels to stiffen and lose function over time, ALT-711 has demonstrated the ability to reverse certain age-related and diabetes-related conditions"
- New Concepts Of Osteoarthritis Pathogenesis And Management Guidelines - Doctor's Guide, 6/14/01 -
"With age, there is increased formation of advanced glycation end products (AGEs),
which results in increased cross-linking of cartilage matrix and activation of cytokines"
-
Carnosine
Nature's pluripotent life extension agent - Life Extension Magazine, 1/01 -
"Carnosine distinctly improved the appearance of the aged mice, whose coat fullness and color remained much closer to that of young animals. Significantly more carnosine-treated mice had
glossy coats (44% vs. 5%), while significantly fewer had skin ulcers (14% vs. 36%) . . . .The sharpest contrast between the treated and untreated mice was seen in their behavior. Only 9% of the untreated mice displayed normal behavioral reactivity, compared to 58% of the carnosine treated mice."
-
Staying
Young Forever, Putting new research findings into practice - Life Extension Foundation, 12/99 -
"The formation of AGE happens in everyone and is a major factor in the aging process itself. These damaged proteins may lead to premature signs of aging (wrinkles and brown
spots) and in the long run to damaging effects on most organ systems within the body . . . The amino acid carnosine is a natural AGE inhibitor found in high concentrations in the brain, muscle tissue and the lens of the human eye. It is also known to be an antioxidant capable of protecting cell membranes and other
cell structures. In vitro studies demonstrated that carnosine inhibits glycosylation and crosslinking of proteins induced by reactive aldehydes, and that it is effective in reducing AGE formation by competing with proteins for binding with the sugars. The authors suggest that this nontoxic compound should be
explored in the treatment of such conditions as diabetic complications, inflammatory disorders, alcoholic liver disease and possibly Alzheimer's disease."
- Drug (ALT-711) Decreases Blood Vessel Stiffness in Older Primates - Medscape, 1/31/01 -
"could be a new treatment for high blood pressure, heart failure, and certain vascular complications of diabetes.
The treatment significantly decreased the stiffness of blood vessels"
- Saving Yourself from AGE - Life Enhancement Magazine, 8/00
- Arginine for Muscles, Memory, Sex and More - Life Enhancement Magazine, 12/99 -
"Free arginine has been shown to help prevent a destructive process known as
cross-linking, which is associated with accelerated aging. Excessive cross-linking reactions inevitably damage the kidneys, necessitating dialysis in advanced age"
- Pimagedine Has Potential For Prevention Of Diabetic Complications - Doctor's Guide, 11/8/01
- Lower AGE with Acetyl L-Carnitine - Life Enhancement Magazine, 8/99 -
"Diabetics and others who become susceptible to high levels of glucose in blood serum as they age
suffer from the formation of deleterious hybrid protein-sugar complexes known as advanced glycation end products (AGE) ... ALC decreased the glycation by 42%"
-
Business
and Science Unite to Fight Aging - Life Extension Magazine, 10/98 -
"One feature of aging and of diabetes is increased stiffness of blood vessels, such as the carotid artery in the neck. Egan showed that in rats, the distensibility of the carotid artery falls by more than
50 percent between 24 and 30 months of age in control animals, but falls by less than 7 percent in animals that received 50 mg/kg of Pimagedine in their drinking water. Further, over the same age interval, the rat heart-weight-to-body-weight ratio rose by about 50 percent in control animals, indicating heart
failure; but the same ratio rose by less than about 7 percent in animals treated with Pimagedine. Pimagedine also normalized left ventricular stiffness and the amount of sugar attached to collagen (connective tissue protein). These are huge anti-aging effects.
But as good as Pimagedine is, ALT-711 may be a great deal better. ALT-711 is something called an "alpha dione cleaving agent." While Pimagedine prevents permanent glucose-protein crosslinks from forming, ALT-711 reverses glucose-protein crosslinks after they have formed. Still better, ALT-711 acts like an artificial
enzyme, breaking crosslink after crosslink without itself being consumed in the reaction. It is as if ALT-711 were a "reverse free radical," setting up a chain reaction of positive, rather than negative, chemical reactions.""
- Advanced Glycation End Products - DrMirkin.com -
"cooking proteins with sugars in the absence of water/ forms advanced glycation products that can damage tissues in the body ... The frightening new news
is that eating foods with these advanced glycation products raises blood and tissue levels and increases nerve damage"
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