This is the summary review from a recent journal that was dedicated to a great debate around the issue of AGEs.
Mol. Nutr. Food Res. 2007, 51, 1075 – 1078
Review
Dietary advanced glycation end products – a risk to
human health? A call for an interdisciplinary debate
Thomas Henle
3 Biological activity of dietary AGEs – two
sides of a medal?
Starting with reports in the mid 1980s of the 20th century,
the formation ofAGEswas linked to consequences of diabetes
[22] and later on to biological disorders such as cataract
or diabetic nephropathy [23, 24]. Artificially prepared
“AGE-proteins” were found to initiate a range of cellular
responses in vitro, including stimulation of monocyte chemotaxis,
secretion of cytokines and growth factors from
macrophages and endothelial cells, and proliferation of
smooth muscle cells [15]. Concerning molecular mechanisms
responsible for cell activation by AGEs, a specific
receptor designated “RAGE” (”receptor for AGEs”) gained
particular interest [36]. Since its first description, a myriad
of papers has been published showing that binding of ligands
to RAGE results in activation of the proinflammatory transcription
factor nuclear factor-kappaB (NF-jB) and subsequent
expression of NF-jB-regulated cytokines [37, 38].
RAGE-AGE interaction thus may trigger cellular dysfunction
in inflammatory disorders. Based on this findings,
RAGE is discussed as a target for drug development [39],
although the structures of possible RAGE-ligands still have
not been identified. Nowadays, it is generally accepted that
AGEs are an important class of uremic toxins, although there
is virtually no information about defined structure-activity
relationships documenting the “toxic” effect of individual
compounds in physiological concentrations [15, 25].
In line with this discussion, it was not a surprise that
questions arose concerning the intake of dietary AGEs via
the daily food and their possible (patho)physiological role
[26]. From the quantitative point of view, the amount of specific
amino acid derivatives ingested with meals from certain
heated foods farly exceed the total amount of AGEs in
the human body. In this context, it was proposed that serum
AGE levels can be influenced by a diet containing AGEs,
and the term “glycotoxins” was created in order to express
that dietary glycation products may represent a risk factor
in diabetic and uremic patients [27]. Indeed, spectacular
reports showed that a high-AGE diet may lead to an
increase in inflammatory markers [28], and concrete dietary
recommendations were published in order to minimize
health risks by avoiding heated foods [29]. On the other
hand, however, these studies must be discussed carefully
due to considerable limitations in the analytical techniques
used.
Furthermore, several recent reports argue against
adverse effects and even discuss positive aspects resulting
from consumption of browned foods. In a cross-sectional
study with hemodialysis patients, it was found that
increased AGEs are not linked to mortality [30]. On a cellular
level, it was found that defined AGEs do not bind to
RAGE, the prominent receptor for AGEs, and do not induce
inflammatory signals, thus arguing against a uniformly role
of AGEs in cellular activation [31, 32]. Furthermore, there
may even be a “chemoprotective” role of individual dietary
AGES due to antioxidative properties or by inhibiting
tumor cell growth [33–35].
4 Conclusion
Physiological consequences resulting from protein-bound
Maillard compounds in foods must be discussed carefully.
This was the idea behind the debate, which is put for discussion
by the papers by Sebekova and Somoza, who argued
for the motion that dietary AGEs are a health risk, and by
Ames, who provided evidence against the motion.
In this
two excellent reviews, numerous arguments based on
papers published in high-impact journals are given for each
of the opinions. The fact that no final conclusion can be
drawn, may reflect the need for a more comprehensive
examination of this issue in the future. For a deeper understanding
of biological consequences resulting from heated
foods, the relationships between well-defined biological
effects and well-characterized chemical structures must be
studied. Prerequisite for this is profound chemistry – pure
compounds, exact concentrations, and unambiguous analytical
techniques. A real “risk assessment” is much too complex
than to leave it up to one discipline alone. It must be a
comprehensive and interdisciplinary approach, joining the
resources of biology, medicine, and chemistry.
While some people are trying to overly interpret and (mis)apply the results of a few small and not well done studies as evidence against consuming fruits, veggies and starchy veggies because of AGEs.....
The bottom line (again) is...
follow the dietary guidelines and principles recommended here and do not worry about your baked yams, potatoes and oatmeal in the context of a healthy diet and lifestyle.
In Health
Jeff
(PS if anyone is really interested in the AGE issue, PM me and I will send you the numerous studies from the full issue for you to fully read.)
[30] Schwedler, S. B., Metzger, T., Schinzel, R., Wanner, C.,
Advanced glycation end products and mortality in hemodialysis
patients, Kidney Int. 2002, 62, 301–310.
[31] Valencia, J. V., Mone, M., Koehne, C., Rediske, J., Hughes, T.
E., Binding of receptor for advanced glycation end products
(RAGE) ligands is not sufficient to induce inflammatory signals:
Lack of activity of endotoxin-free albumin-derived
advanced glycation end products, Diabetologia 2004, 47,
844–852.
[32] Demling, N., Ehrhardt, C., Kasper, M., Laue, M., et al., Promotion
of cell adherence and spreading: A novel function of
RAGE, the highly selective differentiation marker of human
alveolar epithelial type I cells, Cell Tissue Res. 2006, 323,
475–488.
[33] Marko, D., Habermeyer, M., Kemeny, M., Weyand, U., et al.,
Maillard reaction products modulating the growth of human
tumor cells in vitro, Chem. Res. Toxicol. 2003, 16, 48–55.
[34] Somoza, V., Wenzel, E., Lindenmeier, M., Grothe, D., et al.,
Influence of feeding malt, bread crust, and a pronylated protein
on the activity of chemopreventive enzymes and antioxidative
defense parameters in vivo, J. Agric. Food Chem. 2005,
53, 8176–8182.
[35] Chuyen, N. V., Toxicity of the AGEs generated from the Maillard
reaction: On the relationship of food-AGEs and biological-
AGEs, Mol. Nutr. Food Res. 2006, 50, 1140–1149.