X-Message-Number: 24758
Date: Tue, 5 Oct 2004 05:33:43 -0700 (PDT)
From: Doug Skrecky <>
Subject: dietary AGE - adding insult to injury?

J Am Diet Assoc. 2004 Aug;104(8):1287-91.
Advanced glycoxidation end products in commonly consumed foods.
 OBJECTIVE: Advanced glycoxidation end products (AGEs), the derivatives of
glucose-protein or glucose-lipid interactions, are implicated in the
complications of diabetes and aging. The objective of this article was to
determine the AGE content of commonly consumed foods and to evaluate the
effects of various methods of food preparation on AGE production. DESIGN:
Two-hundred fifty foods were tested for their content in a common AGE
marker (epsilon)N-carboxymethyllysine (CML), using an enzyme-linked
immunosorbent assay based on an anti-CML monoclonal antibody. Lipid and
protein AGEs were represented in units of AGEs per gram of food. RESULTS:
Foods of the fat group showed the highest amount of AGE content with a
mean of 100+/-19 kU/g. High values were also observed for the meat and
meat-substitute group, 43+/-7 kU/g. The carbohydrate group contained the
lowest values of AGEs, 3.4+/-1.8 kU/g. The amount of AGEs present in all
food categories was related to cooking temperature, length of cooking
time, and presence of moisture. Broiling (225 degrees C) and frying (177
degrees C) resulted in the highest levels of AGEs, followed by roasting
(177 degrees C) and boiling (100 degrees C). CONCLUSIONS: The results
indicate that diet can be a significant environmental source of AGEs,
which may constitute a chronic risk factor for cardiovascular and kidney

Atherosclerosis. 2002 Aug;163(2):303-11
Lowering of dietary advanced glycation endproducts (AGE) reduces
neointimal formation after arterial injury in genetically
hypercholesterolemic mice.
  Restenosis remains a major cause of morbidity and mortality after
coronary angioplasty. Injury-induced inflammation, thrombosis, smooth
muscle cell (SMC) proliferation, and neointimal formation contribute to
restenosis. These events are linked to circulating glucose-derived
advanced gycation endproducts (AGE), known to promote cell proliferation,
lipid glycoxidation and oxidant stress. This study evaluates the
association between dietary AGE content and neointimal formation after
arterial injury in genetically hypercholesterolemic mice. Male,
12-week-old, apolipoprotein E-deficient (apoE(-/-)) mice were randomly
assigned to receive either a high AGE diet (HAD; AGE=15000 U/mg), or a
similar diet with ten-fold lower AGE (LAD; AGE=1500 U/mg). These mice
underwent femoral artery injury 1 week later, and were maintained on
their diets for an additional 4 weeks. At 4 weeks after injury,
significant decrease in neointimal formation was noted in LAD-fed mice.
Neointimal area, intima/media ratio, and stenotic luminal area (LA) were
less pronounced in the LAD group than the HAD group (P<0.05). These
quantitative differences were associated with a marked reduction
(approximately 56%) of macrophages in the neointimal lesions, as well as
an obvious reduction of SMC content of LAD-fed mice. The reduction of
neointimal formation in the LAD mice correlated with a approximately 40%
decrease in circulating AGE levels (P<0.0005). Immunohistochemistry also
showed a reduced ( approximately 1.5-fold) deposition of AGE in the
endothelia, SMC, and macrophages in neointimal lesions of LAD-fed mice.
These results represent the first evidence in vivo for a causal
relationship between dietary AGE and the vessel wall response to acute
injury, suggesting a significant potential for dietary AGE restriction in
the prevention of restenosis after angioplasty.

Diabetes Metab Res Rev. 2002 May-Jun;18(3):224-37.
Prevention of diabetic nephropathy in mice by a diet low in glycoxidation
  BACKGROUND: Reactive advanced glycation end products (AGEs), known to
promote diabetic tissue damage, occur endogenously as well as in heated
foods and are orally absorbed. The relative contribution of diet-derived
AGEs to diabetic nephropathy (DN) remains unclear. METHODS: We tested a
standard mouse food (AIN-93G) found to be rich in AGEs (H-AGE diet) in
parallel with a similar diet that contained six-fold lower AGE content
(L-AGE), but equal calories, macronutrients, and micronutrients.
Non-obese diabetic mice (NOD) with type 1 diabetes (T1D) and db/db mice
with type 2 diabetes (T2D) were randomly assigned to each formula for
either 4 or 11 months, dur ng which time renal parameters and AGE levels
were assessed. RESULTS: Com pared to the progressive DN and short
survival seen in NOD mice exposed to long-term H-AGE feeding, L-AGE-fed
NOD mice developed minimal glomerular pathology and a modest increase in
urinary albumin:creatinine ratio (p<0.005), and a significantly extended
survival (p<0.0001), consistent with lower serum (p<0.025) and kidney
AGEs (p<0.01). Also, in the 4-month study, and in contrast to the
H-AGE-fed mice, L-AGE-fed NOD and db/db mice exhibited low levels
of renal cortex TGF beta-1 (p<0.05), laminin B1  mRNA (p<0.01) and alpha 1
IV collagen mRNA (p<0.05) and protein, in concert with reduced serum and
kidney AGEs (p<0.05, respectively). CONCLUSION: Intake of high-level,
food-derived AGEs is a major contributor to DN in T1D and T2D mice.
Avoidance of dietary AGEs provides sustained protection against DN in
mice; providing the rationale for similar studies in human diabetic

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=24758