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Home > Anti-aging Research
Advanced Glycation End Product (AGE) inhibitors
- carnosine / alpha lipoic acid / acetyl-l-carnitine / ginseng / gymnema / chromium / Metformin /
- If you do a search of "Aminoguanidine pimagedine", several sites claim they are the same thing. Aminoguanidine is available at International Anti-aging Systems
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:
Consumption of a Diet Low in Advanced Glycation Endproducts for 4 weeks
Improves Insulin Sensitivity in Overweight Women - Diabetes Care. 2013
Aug 19 - "High heat cooking of food induces
formation of advanced glycation endproducts (AGEs), which are thought to
impair glucose metabolism in type 2 diabetic patients. High intake of
fructose might additionally affect endogenous formation of AGEs ... Diets
with high AGE content may increase development of insulin resistance. AGEs
can be reduced by modulation of cooking methods but is unaffected by
moderate fructose intake"
D reduces deposition of advanced glycation end-products in the aortic wall
and systemic oxidative stress in diabetic rats - Diabetes Res Clin Pract.
2013 Mar 20 - "Vitamin D may have an important role
in reducing the risk of cardiovascular disease. Advanced glycation
end-products (AGEs) such as Ne-(carboxymethyl)lysine (CML), have been
implicated in diabetic vascular complications via oxidative stress-mediated
pathways ... Untreated diabetes was associated with significantly elevated
CML levels in the aortic wall (19.5+/-3.3 vs 10.2+/-4.7ng/mL), increased liver
OSI (6.8+/-1.9 vs 3.1+/-0.7), and reduced serum TAC (0.4+/-0.1 vs 0.8+/-0.3mmol
Trolox/L), in comparison with the control group. Cholecalciferol
significantly blocked the accumulation of CML in the aortic wall (10.4+/-8.4
vs 19.5+/-3.3ng/mL), decreased liver OSI (4.2+/-1.4 vs 6.8+/-1.9), and improved
serum TAC (1.0+/-0.2 vs 0.4+/-0.1mmol Trolox/L), compared with the untreated
diabetic group" - See
vitamin D products at iHerb.
Stiffness and Wave Reflections in Relation to Plasma Advanced Glycation End
Products in a Chinese Population - Am J Hypertens. 2013 Feb 28 -
"AGEs accumulate with aging and high cholesterol and
are associated with arterial wave reflections and, in an age-dependent
manner, with arterial stiffness"
Eating deep-fried food linked to increased risk of prostate cancer -
Science Daily, 1/28/13 - "men who reported eating
French fries, fried chicken, fried fish and/or doughnuts at least once a
week were at an increased risk of prostate cancer as compared to men who
said they ate such foods less than once a month ... In particular, men who
ate one or more of these foods at least weekly had an increased risk of
prostate cancer that ranged from 30 to 37 percent. Weekly consumption of
these foods was associated also with a slightly greater risk of more
aggressive prostate cancer ... Deep frying may trigger formation of
carcinogens in food ... Foods cooked with high heat also contain high levels
of advanced glycation endproducts, or AGEs, which have been associated with
chronic inflammation and oxidative stress. Deep-fried foods are among the
highest in AGE content. A chicken breast deep fried for 20 minutes contains
more than nine times the amount of AGEs as a chicken breast boiled for an
hour, for example"
Crusty foods may worsen heart problems associated with diabetes -
Science Daily, 10/22/12 - "We see evidence that
cooking methods that create a crust -- think the edge of a brownie or the
crispy borders of meats prepared at very high temperatures -- produce
advanced glycation end products (AGEs). And AGEs are associated with plaque
formation, the kind we see in cardiovascular disease ... people with higher
rates of cardiovascular complications ate more of these glycated products.
For each unit increase in AGEs intake, a study participant was 3.7 times
more likely to have moderate to high risk for cardiovascular disease ...
Boiling or stewing meat would reduce your AGEs intake further. And
scrambling an egg with cooking spray instead of frying it leads to a
significant reduction in AGEs"
Effects of metformin
on markers of oxidative stress and antioxidant reserve in patients with
newly diagnosed type 2 diabetes: A randomized clinical trial - Clin Nutr.
2012 Aug 21 - "Baseline values of the oxidative
stress markers did not differ significantly between the two groups. In
cases, after three months treatment, there was a significant reduction in
AOPP [Advanced Oxidation Protein Products] (137.52 +/- 25.59, 118.45 +/- 38.42,
p < 0.001), and AGE [advanced glycation end-products] (69.28 +/- 4.58, 64.31 +/-
8.64, p = 0.002) ... Use of metformin is more effective in reducing
oxidative stress compared with lifestyle modification alone" - See
metformin at IAS.
Stop grilling dinner: Specific toxic byproduct of heat-processed food leads
to increased body weight and diabetes, mouse study finds - Science
Daily, 8/20/12 - "mice with sustained exposure to
the compound, methyl-glyoxal (MG), developed significant abdominal weight
gain, early insulin resistance, and type 2 diabetes. MG is a type of
advanced glycation endproduct (AGEs), which is produced when food is cooked
with dry heat. AGEs have been found to lower the body's protective
mechanisms that control inflammation ... In the study, one group of mice was
fed a diet high in MG over four generations, while the control group was fed
a diet without MG ... Over four generations, the mice that ate the MG
started to develop early insulin resistance and increased body fat, whereas
the control group did not have either of these conditions. The researchers
found that MG caused a marked deficiency in protective mechanisms, such as
the survival factor SIRT1 that is present in fat and controls inflammation,
while enhancing the metabolism of glucose and insulin. The ingestion of MG
also adversely affected the activity of an important anti-AGE receptor
called AGER1, which protects SIRT1 and fights insulin resistance ...
clinical guidelines be revised to eliminate foods cooked using dry heat and
replace them with methods that use lower heat or lots of moisture (water) as
in stewing, poaching or steaming. Examples from the AGE-less diet include
stewed beef, chicken and fish instead of grilled meats"
Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on
erectile function in diabetic rats - Int J Impot Res. 2011 Dec 29
intake, cooking practices, and risk of prostate cancer: results from a
multi-ethnic case-control study - Cancer Causes Control. 2011 Dec 30 -
"We observed that high white fish intake was
associated with increased risk of advanced PCA among men who cooked with
high-temperature methods (pan-frying, oven-broiling and grilling) until fish
was well done (p (trend) = 0.001). No associations were found among men who
cooked fish at low temperature and/or just until done"
AMD-like lesions delayed in mice fed lower glycemic index diet - Science
Daily, 11/14/11 - "The dietary glycemic index (DGI)
measures the rate at which glucose is delivered to the bloodstream after
consuming carbohydrates. Higher GI foods including white bread and white
potatoes trigger a rapid delivery of glucose that pushes the body to work
overtime to absorb, whereas lower GI foods, like whole grain bread and
fruits and vegetables, initiate a slower release of glucose that is more
easily processed by cells ... Compared to the mice on the lower GI diet,
mice on the higher GI diet demonstrated elevated accumulations of debris
known as advanced glycation end products (AGEs) in the whole retina,
particularly in the cells of the RPE. The RPE plays a crucial role in
maintaining vision and its dysfunction results in the gradual central vision
loss that is the hallmark of AMD. AGE accumulation has also been linked to
tissue damage in other age-related diseases such as Type 2 diabetes and
Inhibition of advanced glycation end-product formation on eye lens protein
by rutin - Br J Nutr. 2011 Aug 25:1-9 -
"Formation of advanced glycation end products (AGE) plays a key role in the
several pathophysiologies associated with ageing and diabetes, such as
arthritis, atherosclerosis, chronic renal insufficiency, Alzheimer's
disease, nephropathy, neuropathy and cataract. This raises the possibility
of inhibition of AGE formation as one of the approaches to prevent or arrest
the progression of diabetic complications. Previously, we have reported that
some common dietary sources such as fruits, vegetables, herbs and spices
have the potential to inhibit AGE formation. Flavonoids are abundantly found
in fruits, vegetables, herbs and spices, and rutin is one of the commonly
found dietary flavonols. In the present study, we have demonstrated the
antiglycating potential and mechanism of action of rutin using goat eye lens
proteins as model proteins. Under in vitro conditions, rutin inhibited
glycation as assessed by SDS-PAGE, AGE-fluorescence, boronate affinity
chromatography and immunodetection of specific AGE. Further, we provided
insight into the mechanism of inhibition of protein glycation that rutin not
only scavenges free-radicals directly but also chelates the metal ions by
forming complexes with them and thereby partly inhibiting post-Amadori
formation. These findings indicate the potential of rutin to prevent and/or
inhibit protein glycation and the prospects for controlling AGE-mediated
diabetic pathological conditions in vivo" - See
rutin products at iHerb.
Restriction of Advanced Glycation End Products Improves Insulin Resistance
in Human Type 2 Diabetes: Potential role of AGER1 and SIRT1 - Diabetes
Care. 2011 Jul;34(7):1610-6 - "AGE restriction may
preserve native defenses and insulin sensitivity by maintaining lower basal
not an apple a day after all -- it's strawberries: Flavonoids could
represent two-fisted assault on diabetes and nervous system disorders -
Science Daily, 6/27/11 - "fisetin, a
naturally-occurring flavonoid found most abundantly in strawberries and to a
lesser extent in other fruits and vegetables, lessens complications of
diabetes. Previously, the lab showed that fisetin promoted survival of
neurons grown in culture and enhanced memory in healthy mice ... Mice fed a
fisetin-enriched diet remained diabetic, but acute kidney enlargement-or
hypertrophy-seen in untreated mice was reversed, and high urine protein
levels, a sure sign of kidney disease, fell. Moreover, fisetin ingestion
ameliorated anxiety-related behaviors seen in diabetic mice ... blood and
brain levels of sugars affixed to proteins known as advanced glycation
end-products-or AGEs-were reduced in fisetin-treated compared to untreated
Akita mice. These decreases were accompanied by increased activity of the
enzyme glyoxalase 1, which promotes removal of toxic AGE precursors ...
substantial evidence implicates high blood AGE levels with many if not most
diabetic complications ... excessively high AGE levels also correlate with
inflammatory activity thought to promote some cancers. In fact, studies
published by others confirm that fisetin decreases tumorigenicity of
prostate cancer cells both in culture and in animal models ... humans would
have to eat 37 strawberries a day ... Rather than through diet, Maher
envisions that fisetin-like drugs could be taken as a supplement"
AGE Content of Foods - InHuman Experiment, 9/1/09
advanced glycation end products is associated with insulin resistance -
Diabetes Metab Res Rev. 2011 Feb 17 - "On multiple
regression analysis, serum AGEs remained an independent determinant of
HOAM-IR even after adjusting for age, gender, body mass index, waist,
smoking, adiponectin and markers of oxidative stress and inflammation ...
CONCLUSIONS: Formation and accumulation of AGEs progress during normal
aging. We have demonstrated that circulating level of AGEs is associated
with insulin resistance even in non-obese, non-diabetic subjects independent
Inhibition of the receptor for advanced glycation endproducts (RAGE)
protects pancreatic β-cells - Biochem Biophys Res Commun. 2010 Nov 24 -
"Advanced glycation endproducts (AGEs) and the
receptor for AGEs (RAGE) have been linked to the pathogenesis of diabetic
complications, such as retinopathy, neuropathy, and nephropathy. AGEs may
induce β-cell dysfunction and apoptosis, another complication of diabetes
... Inhibition of RAGE prevented AGE-induced pancreatic β-cell apoptosis,
but could not restore the function of glucose stimulated insulin secretion
(GSIS) in rat islets. In summary, the results of the present study
demonstrate that AGEs are integrally involved in RAGE-mediated apoptosis and
impaired GSIS dysfunction in pancreatic β-cells. Inhibition of RAGE can
effectively protect β-cells against AGE-induced apoptosis, but can not
reverse islet dysfunction in GSIS"
Your Skin - ABC News, 11/30/10 - It's a video.
Nutrition and aging skin: sugar and glycation - Clin Dermatol. 2010
Jul-Aug;28(4):409-11 - "The effect of sugars on
aging skin is governed by the simple act of covalently cross-linking two
collagen fibers, which renders both of them incapable of easy repair.
Glucose and fructose link the amino acids present in the collagen and
elastin that support the dermis, producing advanced glycation end products
or "AGEs." This process is accelerated in all body tissues when sugar is
elevated and is further stimulated by ultraviolet light in the skin. The
effect on vascular, renal, retinal, coronary, and cutaneous tissues is being
defined, as are methods of reducing the glycation load through careful diet
and use of supplements"
Glycation End Products in Foods and a Practical Guide to Their Reduction in
the Diet - J Am Diet Assoc. 2010 Jun;110(6):911-916.e12 -
"Modern diets are largely heat-processed and as a
result contain high levels of advanced glycation end products (AGEs).
Dietary advanced glycation end products (dAGEs) are known to contribute to
increased oxidant stress and inflammation, which are linked to the recent
epidemics of diabetes and cardiovascular disease ... Based on the findings,
dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked
state across food categories. Animal-derived foods that are high in fat and
protein are generally AGE-rich and prone to new AGE formation during
cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits,
whole grains, and milk contain relatively few AGEs, even after cooking. The
formation of new dAGEs during cooking was prevented by the AGE inhibitory
compound aminoguanidine and significantly reduced by cooking with moist
heat, using shorter cooking times, cooking at lower temperatures, and by use
of acidic ingredients such as lemon juice or vinegar"
Metformin restores impaired HDL-mediated cholesterol efflux due to glycation
- Atherosclerosis. 2009 Mar 19 - "In the presence of
metformin or aminoguanidine (100mM), glycated HDL-mediated cholesterol
efflux was restored to 97.5+/-4.3% and 96.9+/-3.1%, respectively"
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"
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
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
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
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.
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
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
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
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"
II Data Show Alagebrium Reduces Arterial Stiffness in Elderly With Isolated
Systolic Hypertension - Medscape, 11/23/05
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 -
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)"
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
- Ramipril Reduces Advanced Glycation End Products In Non-Diabetic Nephropathy - Doctor's Guide, 4/21/03 -
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.
vitamin C products.
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"
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
- 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 -
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
Antioxidants Aren't Enough - Life Extension Magazine, 1/02
- Oxidative Marker Found In Rheumatoid Arthritis Synovial Tissue - Doctor's Guide, 6/12/02 -
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
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"
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"
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."
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%"
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"