Here are some differing views on glycation causes from people advocating low-carb, high-carb, and moderate-carb diets (summary of identified causes in parentheses):
Ron Rosedale, MD: (glucose, starch and other carbohydrates)
"In everyone, when one eats starches it quickly turns to sugar, glucose, fructose, galactose, etc. that will circulate and glycate the collagen that lines the arteries causing inflammation and cardiovascular disease and all of the other adverse effects of glycation."
“glucose will cause some damage when above 0 mg/dl …. At any level of glucose compatible with life some more meaningful degree of glycation, hormonal response and genetic expression will take place.”
From: November 20, 2011, http://drrosedale.com/blog/2011/11/22/is-the-term-safe-starches-an-oxymoron/
Jimmy Moore: (glucose)
“a process known as glycation–where the glucose (sugar) in your blood finds proteins to stick to to form what is know as advanced glycation end products, aka AGEs. As the acronym implies, these ages will age you. The more sugar you eat, the more ages that get produced.”
From: Low-Carb Diet Prevents Sagging Skin, Prostate Tumor Growth, And Hypercholesterolemia
November 26th, 2007
Nora Gedgaudas: (nonfibrous carbohydrates)
"All nonfibrous carbohydrates stimulate the secretion of insulin, which is the fat storage hormone, or damage the body and brain via a process known as [i]glycation[/i] (in which sugars in the bloodstream react with proteins and fats and cause them to deteriorate). ...
Glycation and its damage is ultimately a cumulative process, so every bit of sugar or starch we eat eventually counts. Every piece of candy, cookie, bread, or potato, every spoonful of honey, and every drop of soda effectively shortens your life—something to think about."
From: Primal Body, Primal Mind, c. 2011, pp. -127
Ray Peat, PhD: (oxidized PUFA’s, repeated cellular stress, inadequate carbon dioxide)
"Glycation is something that is identified with diabetes and alzheimer's disease and so on. It means the attachment of sugar-like fragments to proteins and especially to receptors, or sensitive points in the cell (regulatory points). ... [T]hey call it glycation as if it's caused by glucose, but actually, the oxidized products of PUFA's are many times more active in causing glycation, and the glycation happens mainly on lysine amino groups of proteins, but you can glycate any molecule that has an amino group, and that pretty well inactivates it, but the normal function of a good concentration of carbon dioxide is to bind to glycine groups [and thus prevent glycation]."
From: (2005-10) Ray Peat - Nervous System Protect & Restore, https://www.youtube.com/watch?v=mdLHWFJI2y0, starting at 1:00:54
“The free fatty acids released by the stress hormones serve as supplemental fuel, and increase the consumption of oxygen and the production of heat. (This increased oxygen demand is a problem for the heart when it is forced to oxidize fatty acids. [A. Grynberg, 2001]) But if the stored fats happen to be polyunsaturated, they damage the blood vessels and the mitochondria, suppress thyroid function, and cause “glycation” of proteins. They also damage the pancreas, and impair insulin secretion.
A repeated small stress, or overstimulation of insulin secretion, gradually tends to become amplified by the effects of tryptophan and the polyunsaturated fatty acids, with these fats increasing the formation of serotonin, and serotonin increasing the liberation of the fats.
The name, “glycation,” indicates the addition of sugar groups to proteins, such as occurs in diabetes and old age, but when tested in a controlled experiment, lipid peroxidation of polyunsaturated fatty acids produces the protein damage about 23 times faster than the simple sugars do (Fu, et al., 1996). And the oxidation of fats rather than glucose means that the proteins won't have as much protective carbon dioxide combined with their reactive nitrogen atoms, so the real difference in the organism is likely to be greater than that seen by Fu, et al.
These products of lipid peroxidation, HNE, MDA, acrolein, glyoxal, and other highly reactive aldehydes, damage the mitochondria, reducing the ability to oxidize sugar, and to produce energy and protective carbon dioxide.”
From: Glycemia, starch, and sugar in context, c. 2009
"Glycation imitates mutated forms of proteins, for example normal transthyretin behaves like the prion protein, forming amyloid. Transthyretin, the protein that carries thyroid hormone and vitamin A, is normally taken up along with cholesterol under the influence of thyroid hormone. Abnormal cholesterol metabolism is one of the traits associated with Alzheimer's disease. In the absence of thyroid-supported respiration, carbon dioxide and other respiration-associated molecules (e.g., acetate) are replaced by lactate and unused sugar, causing abnormal modifications of proteins such as tau, which regulates microtubule assembly. Glycation of collagen in the extracellular matrix alters the properties of the matrix. The glycated matrix would become a preferred site for glycated prion-like proteins.
It is possible that the altered transthyretin makes vitamin A less available to cells. Vitamin A deficiency creates major disruption of the framework proteins. Fragments of starch molecules inhibit the enzymes that remove inappropriately bound sugar molecules from proteins, and the inability to metabolize sugar into carbon dioxide increases that binding. Starches and unsaturated fats cooperate in this process of inappropriate sugar binding, while thyroid hormone, and the carbon dioxide it produces, tend to prevent the binding.
Considering the universal importance of carbon dioxide to life, the ways it interacts with all of the important substances that make up organisms, that it is involved closely with ATP synthesis and other "energy-related" processes, that it participates intimately in the regulation of water and ions, that it is therapeutic in a range of conditions including angina pectoris, hypoxia, epilepsy, inflammation, shock, lipid peroxidation, pneumonia, and asthma, I think we can at least conclude that it is a largely overlooked mediator between chemical energy and life processes. In many cases, its movements and reactions constitute the actual motive force that so many fantasy theories have failed to explain. In other situations, it fills out the context for understanding the energy-mediating actions of ATP, calcium, and hormones."
From: Energy, structure, and carbon dioxide: A realistic view of the organism, http://members.westnet.com.au/pkolb/peat2.htm
Chris Masterjohn, PhD: (oxidative stress, PUFAs, dicarbonyls, depleted glutathione)
... There are a lot of misconceptions about AGEs, and one of them is that they are mostly formed from glucose directly glomming on to proteins. The term "glycation," which is clearly derived from "glucose," certainly contributes to this misconception, but the situation is actually much more complex than this. Glucose does indeed have the hots for proteins, but the high school glycation prom has a sexy chaperone named fructosamine 3-kinase who's kicking carbonyls and taking names, and if the two dance too close, F3-K steps in the way.
It is instead the sneaky dicarbonyls (pronounced like "DIE-carb-o-NEELS") that escape the attention of our otherwise striking chaperone. They are on average 20,000 times more reactive than glucose, and they emerge from the broken pieces of glucose, protein, and fat — and not just PUFAs. Nevertheless, they do no harm unless they slip past our good friend glutathione, who polices the streets at night and renders the balance of these creepy would-be criminals as impotent as the mythical sorcerer lurking in the shadows of Maasai-land. ...
most AGEs in plasma are derived from methylglyoxal and 3-deoxyglucosone (13), and that it is methylglyoxal-derived AGEs that increase the most in diabetes...
peroxidation of PUFAs is very unlikely to be a major source of AGEs.
Are PUFAs off the hook? Not at all. We will see below that oxidative stress is a central factor in AGE formation, and guzzling corn oil gets that oxidative stress a-goin'.
... Treatments that deplete cells (27) or live animals (28) of their glutathione cause large increases in methylglyoxal concentrations, suggesting that the glyoxalase system is ordinarily efficiently detoxifying much or most of the methylglyoxal that crosses its path. Little is known about the molecular mechanisms by which our cells regulate their production of the two glyoxalase enzymes themselves, but we know so far that zinc and insulin increase the production of glyoxalase-1 (29). This suggests that zinc, insulin, and glutathione are critical components of our defense against dicarbonyls and the AGEs they produce.
... oxidative stress depletes glutathione
... AGEs and their dicarbonyl precursors may emerge as key signaling molecules, but ... in many situations they do indeed cause harm.
From: Where Do Most AGEs Come From? O Glycation, How Thy Name Hast Deceived Me!
Friday, October 7, 2011