Biodistribution and
metabolism of the
Maillard reaction
products
Frederic J Tessier
Frederic.tessier@isab.fr
Dietary ingestion
of food-derived
Maillard reaction
products
The Maillard reaction
products (MRPs) biodistribution 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.
MRP classification according to Finot and Furniss [1]
R-NH2
+
Reducing Sugar
Schiff Base
rearrangement
Advanced Glycation End-products (AGEs) and other
Advanced Maillard reaction products
Pre-melanoidins
Polymerization of the high
reactive intermediates
Melanoidins
Brown nitrogenous polymers,
Insoluble high molecular weight species
Maillard Reaction products (MRPs)
Amadori product (ketoamine)
Chemical structures
represented by triangles as
followed:
Well-known
Partially
identified
Mainly
unidentified
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
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]
Bio-distribution and Metabolism of the Amadori product
Dietary
Ingestion
Intestinal
digestion
of proteinbound FL
Microbial
degradation
of FL in the
hind gut
Passive
diffusion
Systemic
circulation
Kidneys
Liver
Elimination of FL
within 12h after
ingestion
Urine
Very low level of FL
Feces
1% in adults
3% of protein-bound FL (Humans)
60% of free FL, and 10% of protein-bound FL (Rats)
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]
Bio-distribution and Metabolism of food-derived AGEs *
Dietary ingestion
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]
Tissues
10% absorbed
Systemic
circulation
Liver
* AGE content measured by ELISA [11]
Some dietary
AGE derivatives
react with
endogenous
proteins in the
blood & tissues
Kidneys
Urine
30% excreted
(of the 10% absorbed)
Bio-distribution and Metabolism of food-derived AGEs
Some dietary AGE analogs react with
tissue proteins such as collagen
LDL
AGE-receptor
Some dietary AGE analogs bind to the
cellular receptors for AGEs (i.e. RAGE)
at the surface of cells
Systemic
circulation
Cell
LDL
LDL
Liver
Kidneys
Urine
And may induce
-Intracellular oxidative stress
-Endocytosis and removal of AGEs
Some dietary AGE analogs react with
circulating proteins such as LDL
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]
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
Feces 70 to 90% (Rats)
Urine
1 to 5% (Rats)
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)
Feces
Clostridia (detrimental on host health)
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
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