nearly all [studies involving actual health and risk factor outcomes] "simply generate high- and low-AGE diets, generally by cooking the same foods (human diets or rodent lab chow) at different temperatures." Eg, you'll note in my post above that I had actually quoted one such example (reference 5 in that post): "Thus, we conducted a randomized, crossover, intervention trial to clarify whether a habitual diet containing high-heat-treated foods, such as deep-fried potatoes, cookies, brown crusted bread, or fried meat, could promote risk factors of type 2 diabetes or cardiovascular diseases in healthy people." Similarly, (1) below (cited by Sillewater) and this and several other studies included in the CR Society posting I'd linked, just looked at the AGE content of the actual, self-selected diets of subjects.
Well... you cited such a study in one of your previous posts on the topic:
Single oral challenge by advanced glycation end products acutely impairs endothelial function in diabetic and nondiabetic subjects. (PMID 17496238).
Well, first, even that study did not use "analogues produced in a lab and fed in isolation (Like most AGE studies I've read?)", as you'd suggested in the post to which I was responding, but caramelized sugar created by conventional cooking. But yes, I do agree that this was a rather artificial study. I didn't say that there were
no such studies -- just that "
nearly all such studies "simply generate high- and low-AGE diets, generally by cooking the same foods (human diets or rodent lab chow) at different temperatures." "
Regarding the heat treated foods you mentioned, allow me to bold the key words here: "high-heat-treated foods, such as deep-fried potatoes, cookies, brown crusted bread, or fried meat." We're supposedly looking at the relationship between AGE consumption and occurence of type 2 diabetes and CVD, yet how are we correcting for the inclusion of sugars, starches, and foods fried in seed-oils?
Once again: the way you " correct for the inclusion of sugars, starches, and foods fried in seed-oils" is "by cooking
the same foods (human diets or rodent lab chow) at different temperatures." Thus, in the study under discussion, "Both diets were designed to contain comparable amounts of energy and nutrients (53% of energy from carbohydrates, 15% of energy from proteins, and 32% of energy from lipids)." Looking at their Table 1, the the STD (standard, high-AGE diet) contained more sat fat, less MUFA, and the same amount of n6 and n3 PUFA as the STMD (Steamed, low-AGE diet); then, "The STD was prepared by using conventional techniques such as grilling, frying, and roasting and contained industrial food known to be highly cooked.” Ie, the same meat, vegetables, or “starches,” but poached vs. roasting or frying, or baked at low vs. high temperatures; they even went so far as to use heat-extruded vs. steamed corn flakes, dry cookies vs. sponge cake, and well-baked bread with brown crust vs. "mildly baked bread.” Similarly, in (3) below, "Two study diets were designed to have similar content of calories, protein, carbohydrate, and fat but differ by ~5-fold in AGE content, based on CML content (4G9 mAb), by varying the cooking time and temperature;" again,in (2), "To vary the AGE content, foods, particularly meat, were exposed to different cooking methods. L[ow]-AGE subjects were instructed to boil, poach, stew or steam, avoid fried entrees, and reheat food indirectly using steam in a double boiler. H[igh]-AGE participants were instructed to roast, broil and oven fry foods as usual. " Whatever you think of the specific foods used falls out of it when you use the same foods but prepared to be high vs. low in dietary AGE. (It's also worth noting, IAC, that the largest sources of dietary AGE come from cooking meat, not foods we would agree are crappy like breads and sugary desserts, because of the fat and protein already in the stuff; even if you add no oil or butter to meat at all, lowering the temperature can substantially cut this back, but any meat is still vastly higher than any vegetable, bread, or even PUFA-fried potato chips or french fries(1)).
There are even significant holes in this study:
A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases (PMID 20335546).
No luck in getting the full text version at this point, but I noticed something suspicious in the results section of the abstract:
"RESULTS: In comparison with the steamed diet, 1 mo of consuming the high-heat-treated diet induced significantly lower insulin sensitivity and plasma concentrations of long-chain n-3 (omega-3) fatty acids and vitamins C and E [-17% (P < 0.002), -13% (P < 0.0001), and -8% (P < 0.01), respectively]. However, concentrations of plasma cholesterol and triglycerides increased [+5% (P < 0.01) and +9% (P < 0.01), respectively]."
What is suspicious about this? Among other things, the decrease in plasma concentration of vitamin C and the increase in trigs. These are usually telltale signs of a diet rich in refined carbohydrates and sugars.
Low vitamin C results from high oxidative stress, and high TG results from insulin resistance, both of which extensive studies clearly show to be unduced by a high-AGE diet.
And here's another study that I found suspect:
Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inflammatory Response, Oxidative Stress, and Aging (PMID 17452738)
This study seemed initially promising because the researchers controlled for caloric intake: "The consumption of dietary AGEs, but not of calories, correlated independently with circulating AGEs (CML: r = 0.415, p =.0001 and MG: r = 0.282, p =.002) as well as with high sensitivity C-reactive protein (hsCRP) (r = 0.200, p =.042)."
However, some of the results appear to be based on unstable beta coefficients and related estimates. Take a look at Table 2, for example:
http://www.ncbi.nlm....45629/table/T2/
[BIG SNIP!]
I don't think statistical slicing and dicing gets one very far, especially in light of clear results in so many models, and especially the very narrowly-controlled animal feeding studies.
But what is CML? It is carboxymethyl-lysine. And what kind of diet leads to particularly high serum CML levels? A vegetarian diet:
http://www.biomed.ca...3/krajcovic.htm
First, that's serum CML, not dietary CML, the latter of which is the subject at hand; and the determinants of high serum CML were not evaluated in that study, nor were the dietary AGE per se. Again: such issues are resolved by doing controlled, intervention-based studies, using "high- and low-AGE diets, generally by cooking
the same foods (human diets or rodent lab chow) at different temperatures." And second, the subject at hand is (again) dietary AGE, not vegetarianism.
Anyways, my point here is that the studies linking exogenous AGEs to health problems aren't even close to damning.
Well, what can I say? I really think there's more than enough evidence to say that they
are.
I don't see that it in any way impacts the current discussion: the fact that humans evolved to better exploit meat, and may have also been changed to adapt to nutritional changes resulting from cooking, doesn't tell you whether eating more or less of a given food or food prepared in one way or another is healthier for you.
Selective pressures among our ancestors were definitely reduced post-reproductive age, but there are some things to consider. For example, men can have children at very advanced ages. Also, and this is particularly important, human infants are rather vulnerable. So ancestral parents and grandparents had to look after them. That generated selection pressure for survival at older ages. Not to mention, in tribal environments where polygamy is practiced, it is not uncommon for older men to have several younger wives. There are a few interesting things about evolution that are not so obvious. One is that a very small selection pressure can lead traits to evolve fast - e.g., in a few hundred years, not the millions of years that many think are necessary.
But, granting all that, it still doesn't change what I said above ...
References1: Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE,
Vlassara H. Advanced glycation end products in foods and a practical guide to
their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12. PubMed
PMID: 20497781.
2: Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, He C, Vlassara H. Restriction of
dietary glycotoxins reduces excessive advanced glycation end products in renal
failure patients. J Am Soc Nephrol. 2003 Mar;14(3):728-31. PubMed PMID: 12595509.
3: Vlassara H, Cai W, Crandall J, Goldberg T, Oberstein R, Dardaine V, Peppa M,
Rayfield EJ. Inflammatory mediators are induced by dietary glycotoxins, a major
risk factor for diabetic angiopathy. Proc Natl Acad Sci U S A. 2002 Nov
26;99(24):15596-601. Epub 2002 Nov 12. Erratum in: Proc Natl Acad Sci U S A. 2003
Jan 21;100(2):763.. PubMed PMID: 12429856; PubMed Central PMCID: PMC137762.
