Advanced glycation end products (AGEs) in diet predicts blood AGEs

[Guest guest]

Hi All,

The level of AGEs in the diet appears to correlate, and probably cause, the

level

that is seen in the blood, for the below.

In the pdf-available below, Fig. 1 showed that the level of AGEs in the normal

subject diets was a fairly straight line with the level of AGEs in the blood.

If no

AGEs were eaten, the level was a third of that for the highest, according to the

straight line joining widely scattered points. The difference between the 0

dietary

AGEs and the average level of dietary AGEs corresponded to a ~2-fold higher

level of

blood AGEs.

Uribarri J, Cai W, Sandu O, Peppa M, Goldberg T, Vlassara H.

Diet-Derived Advanced Glycation End Products Are Major Contributors to the

Body's

AGE Pool and Induce Inflammation in Healthy Subjects.

Ann N Y Acad Sci. 2005 Jun;1043:461-6.

PMID: 16037267

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=16037267 & query_hl=36

INTRODUCTION

Advanced glycation end products (AGEs) are a heterogeneous group of compounds

with

significant prooxidant and proinflammatory actions.1,2 They form in the body

under

physiologic conditions produced by the reaction of reducing sugars and reactive

aldehydes with the free amino group of proteins, lipids, and nucleic acids.3

Their

rate of endogenous formation is markedly enhanced in diabetes mellitus.2 They

also

form externally during the heat processing of food.4,5 The potential biological

role

of these exogenous AGEs has generally been ignored because of the assumption

that

they undergo negligible gastrointestinal (GI) absorption. Recently, however, it

has

become apparent that dietary AGEs contribute significantly to the body's AGE

pool,6-9 and may play a significant pathogenic role in a variety of disease

states.7-15 We will review formation of AGEs during the cooking of food, their

GI

absorption, and their biological effects. Finally, we will briefly discuss new

information on dietary AGEs derived from studies on a large cross-section of

healthy

subjects.

Heat treatment of foods containing sugars and/or lipids and proteins may result

in

the formation of AGEs. This nonenzymatic reaction is also called the Maillard

reaction in honor of the French chemist who examined the reaction between

glycine

and glucose in 1912.4

Several factors are known to affect AGE generation in foods, including nutrient

composition, temperature, humidity, pH, and duration of cooking.4,5 A large

database

with the contents of N-carboxymethyl-lysine (CML), a commonly measured AGE, in

more

than 200 food items has recently become available.5 The average AGE content for

each

food group classified as per the American Diabetes Association exchange lists is

shown in Table 1, adapted from reference 5. In general, foods high in lipid and

protein content exhibit the highest AGE levels; for example, the fat and meat

groups

contain 30- and 12-fold higher AGE content than the carbohydrate group,

respectively.5 Temperature and method of cooking appear to be more critical to

AGE

formation than time of cooking. This is evidenced by the higher AGE values of

samples broiled or grilled at temperatures of 230°C for shorter cooking times

when

compared to samples boiled in liquid media at 100°C for longer periods.5

Clearly,

meat and meat-derived products, processed by high, dry heat such as in broiling,

grilling, frying, and roasting are major sources of AGEs. Since these foods are

commonly consumed in the USA, most people are constantly on a high-AGE diet. In

fact, when we actually estimated the daily AGE consumption, based on analyses of

three-day food records from 90 healthy subjects, the average value was 16,000 ±

5000

AGE kilo units/day (mean ± SD).

TABLE 1. AGE content of selected food items a

...........................................

Food item AGE content

...........................................

Fats

Almonds, roasted 66.5 kU/g

Oil, olive 120 kU/g

Butter 265 kU/g

Mayonnaise 94 kU/g

Proteins

Chicken, broiled (15 min) 58 kU/g

Chicken, fried (15 min) 61 kU/g

Beef, boiled (60 min) 22 kU/g

Beef, broiled (15 min) 60 kU/g

Tuna, roasted (40 min) 6 kU/g

Tuna, broiled (10 min) 51 kU/g

Cheese, American 87 kU/g

Cheese, brie 56 kU/g

Tofu, raw 8 kU/g

Tofu, broiled 41 kU/g

Carbohydrates

Bread, whole wheat 0.5 kU/g

Pancakes, homemade 10 kU/g

Apples 0.13 kU/g

Bananas 0.01 kU/g

Carrots 0.1 kU/g

Green beans 0.2 kU/g

............................................

a Data from Goldberg et al.5

NOTE: AGE denotes CML-like immunoreactivity, assessed by ELISA (4G9mAb)

INTESTINAL ABSORPTION OF AGEs

The intestinal absorption of AGEs has long been demonstrated yet ignored because

of

its small magnitude.16 Recent studies on human subjects, however, have shown a

significant increase in plasma AGE levels within two hours following the oral

administration of a single AGE-rich meal.6 To address this issue further, normal

Sprague-Dawley rats were fed single- and double-labeled AGE-modified protein

diet

preparations; within a few hours serum peaks of these radiolabeled AGEs were

easily

demonstrated.17

Several animal studies have shown a correspondence between dietary AGE content

and

serum and tissue AGE levels.10-15 Moreover, studies in diabetics and renal

failure

patients have shown a significant association between dietary and circulating

AGE

levels.7-9

All the above data demonstrate that food-derived AGEs are directly absorbed into

the

circulation and contribute to the body's AGE pool. The exact mechanism for this

absorption, however, remains unclear at present.

BIOLOGICAL EFFECTS OF FOOD-DERIVED AGEs

Food-derived AGEs induce protein cross-linking and intracellular oxidant stress

similar to their endogenous counterparts when tested in vitro using

human-derived

endothelial cells.18 These prooxidant and proinflammatory properties are also

found

in the circulating AGE fractions derived from these exogenous AGEs. For

instance,

low-density lipoprotein (LDL) samples obtained from diabetic subjects exposed to

a

high-AGE diet for several weeks led to a marked increase in MAPK

phosphorylation,

NF-B activity, and VCAM-1 secretion when added to cultured human endothelial

cells.19 These results were in contrast to the response to LDL extracted from

diabetic subjects under similar glycemic control but exposed to a low-AGE

diet.19

Experiments performed in different animal models have established a significant

role

for dietary AGEs in inducing type 1 diabetes mellitus in nonobese diabetic (NOD)

mice,10 insulin resistance in db/db (+/+) mice,11 atherosclerosis in

apoE-deficient

mice,12,13 diabetic nephropathy,14 or wound healing in NOD and db/db (+/+)

mice.15

In a group of diabetic subjects, dietary AGE restriction was associated with

significant reduction of two markers of inflammation, plasma C-reactive protein

(CRP) and peripheral mononuclear cell TNF-, as well as of VCAM-1, a marker of

endothelial dysfunction.7 These observations were later extended to chronic

renal

failure patients on maintenance peritoneal dialysis, in whom dietary AGE

restriction

was associated with a parallel reduction of serum AGEs and CRP.8 The parallel

changes of serum AGEs and CRP following dietary AGE modifications are highly

suggestive of a role for dietary AGEs in inducing inflammation.

More recently, a group of diabetic patients underwent testing of flow-mediated

vasodilatation (FMD) in response to the single oral administration of an

AGE-rich

beverage (without any glucose). Ninety minutes later, serum AGEs increased,

while

FMD response was markedly impaired.20 These findings demonstrate an acute

harmful

effect of dietary AGEs on endothelial function.

STUDIES IN HEALTHY SUBJECTS

We recently performed a cross-section analysis of 90 healthy subjects.

Demographic

data, three-day food records, and fasting blood were obtained during the

subjects'

usual activity and diet. Subjects were given detailed instructions on how to

record

three-day food records, including cooking methods. A database with the AGE

content

of a large number of food items was used to estimate the AGE content of food.5

AGEs

were measured by ELISA using a monoclonal antibody against CML. We found

significant

correlation between dietary AGE content and serum AGEs (Fig. 1), and CRP.

A subgroup of five healthy subjects was exposed to short-term dietary AGEs

restriction (daily AGE content reduced fourfold). This reduction of dietary AGEs

intake was associated with an average decrease of serum AGE levels by 30-40%.

These

data match previous findings in diabetics and renal failure patients,7-9 and

imply a

major quantitative contribution of dietary AGEs to the body's AGE pool. Figure 2

depicts our current understanding of the factors regulating circulating AGE

levels.

In summary, the information reviewed above demonstrates that dietary AGEs,

present

in abundance in food commonly consumed in a " Western-style " diet, contribute

significantly to the body's AGE pool. Moreover, these diet-derived AGEs have a

significant association with indicators of inflammation in healthy subjects.

Together with previous evidence in diabetics and renal failure patients, these

data

suggest that dietary AGEs may play an important role in the causation of chronic

diseases associated with underlying inflammation. The findings also highlight

the

importance of consuming diets with low AGE content as a preventive measure.

Al Pater, PhD; email: old542000@...

__________________________________________________