Diapositive 1

1
Biodistribution and metabolism of the Maillard
reaction products Frederic J Tessier Frederic.tes
sier_at_isab.fr
2
The Maillard reaction products (MRPs)
bio-distribution and metabolism are not
completely understood but advances have been
made. MRPs are usually classified as early MRPs,
advanced MRPs and Melanoidins. These different
groups of MRPs have been tested in animal
experiments. However, only the early MRPs
(Amadori product) has been investigated in human
studies.
Dietary ingestion of food-derived Maillard
reaction products
3
MRP classification according to Finot and Furniss
1

R-NH2
Reducing Sugar
Chemical structures represented by triangles as
followed
Schiff Base
Well-known
Amadori product (ketoamine)
rearrangement
Advanced Glycation End-products (AGEs) and
other Advanced Maillard reaction products
Partially identified
Maillard Reaction products (MRPs)
Pre-melanoidins
Polymerization of the high reactive intermediates
Melanoidins Brown nitrogenous polymers, Insoluble
high molecular weight species
Mainly unidentified
4
Example of foods which may contain MRP
Raw foods have almost no MRP
Bread, biscuit, chocolate, breakfast cereals may
contain high level of Amadori product. Heated
milk, infant milk formula are two example of
beverage which contains lactulosyllysine (Amadori
product)
French fries, potato chips, coffee contains
acrylamide Grilled meat contains heterocyclic
amines According to an ELISA test, many foods
contain carboxymethyllysine
Bread crust, cookies, coffee, chocolate contain
melanoidins
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Bio-distribution and Metabolism of the Amadori
product

• Several experiments were performed mainly with
  fructoselysine (FL) 2
• FL was the only MRP administered in human trials
  3
• FL is not available as a source of lysine
• FL is transported out of the intestine by passive
  diffusion
• In rats, at least 60 of orally ingested free FL
  are excreted in the urine 4
• In humans, urinary excretion of ingested
  casein-bound FL is 3 3
• Lactuloselysine (Amadori product form milk) is
  poorly digested 5
• There is an uptake of FL into the cells of the
  liver and muscles by passive diffusion
• Microorganisms destroy the Amadori product in the
  large intestine
• High excretion rate for human infants 16 in
  urine 55 in faeces 6

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Bio-distribution and Metabolism of the Amadori
product
Dietary Ingestion
Passive diffusion
Systemic circulation
Intestinal digestion of protein-bound FL
Microbial degradation of FL in the hind gut
Kidneys
Liver
Elimination of FL within 12h after ingestion
Urine
3 of protein-bound FL (Humans)
Very low level of FL 1 in adults
Feces
60 of free FL, and 10 of protein-bound FL
(Rats)
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Bio-distribution and Metabolism of the advanced
MRPs
The structural diversity and the wide range of
molecular weights of the advanced MRPs make
difficult to summarized their biodistribution and
metabolism Ne-carboxymetyllysine (CML),
acrylamide, 5-hydroxymethyl-furfuraldehyde (HMF),
dicarbonyls, heterocyclic amines are some example
of advanced MRPs which have been studied
individually.

• Dietary ingested Acrylamide is easily absorbed
  through the intestine tract, rapidely metabolized
  and excreted. However acrylamide and its
  metabolites can accumulate in the body when bound
  to protein in nervous system tissues or
  hemoglobin in blood.
• Heterocyclic amines are also easily absorbed and
  metabolized through phase-I enzyme systems 7
• HMF has been shown to accumulate in kidneys,
  bladder and liver of rats 8
• CML, a well-known AGE or advanced MRP, has been
  quantified in many foods. CML can be also formed
  endogenously. However Liardon et al. assumed that
  the dietary CML is the main source of the urinary
  CML 9

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Bio-distribution and Metabolism of food-derived
AGEs
Based on a human study, Koshinsky et al.
calculated that the total amount of orally
absorbed AGEs found in blood was equal to 10 of
that estimated to be present in the ingested
meal. Of that, only 30 was excreted in the urine
of persons with normal renal function 10
Dietary ingestion of food-derived AGEs
Tissues
10 absorbed
Some dietary AGE derivatives react with
endogenous proteins in the blood tissues
Systemic circulation
Liver
Kidneys
AGE content measured by ELISA 11
30 excreted (of the 10 absorbed)
Urine
9
Bio-distribution and Metabolism of food-derived
AGEs
Some dietary AGE analogs react with tissue
proteins such as collagen
AGE-receptor
Some dietary AGE analogs bind to the cellular
receptors for AGEs (i.e. RAGE) at the surface of
cells
Systemic circulation
Cell

• And may induce
• Intracellular oxidative stress
• Endocytosis and removal of AGEs

LDL
Liver
Kidneys
Some dietary AGE analogs react with circulating
proteins such as LDL
Urine
10
Bio-distribution and Metabolism of the melanoidins

• Experiments were performed mainly on rats and
  reviewed recently by Faist and Erbersdobler 12
• The difficulty to study the biodistribution and
  metabolism of melanoidins is that their chemical
  structure remains almost unknown
• The absorption of the melanoidins is dependent of
  their molecular weight and solubility. The
  absorption of the low molecular weight and water
  soluble melanoidins seems to be favored 13
• In rats 70 to 90 of orally ingested melanoidins
  are excreted in the feces, and only 1 to 5 in
  urine 14,15,16

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Bio-distribution and Metabolism of the melanoidins
Limited absorption by the intestines
Systemic circulation
Suspected digestive or microbial degradation of
melanoidins
Apparently not utilized by the organism, and
excreted
Liver
Kidneys
Urine
Feces
1 to 5 (Rats)
70 to 90 (Rats)
12
Bio-distribution and Metabolism of the melanoidins
Colon
Melanoidins and other MRPs affect the microflora
composition in the gut
Using an in vitro gut model Tuohy et al. found
that glycated bovine serum albumin reduces
numbers of bifidobacteria and increases number of
clostridia 17
Bifidobacteria (beneficial on host
health) Clostridia (detrimental on host health)
Feces
13
References

• Finot Furniss, 1989
• Erbersdobler Faist, 2001
• Lee Erbersdobler, 1994
• Finot Magnenat, 1978
• Finot, 1973
• Niederweiser et al., 1975
• Shina et al., 1994
• Germond et al., 1987
• Liardon et al., 1987
• Koschinsky et al., 1997
• Makita et al., 1992
• Faist Erbersdobler, 2001
• Nair et al., 1981
• Valle-Riestra Barnes, 1969
• Finot Magnenat, 1981
• Homma Fujimaki, 1981
• Tuohy et al., 2005