Sunday, January 11, 2015

Glycation Causes – Carbs, PUFAs, Oxidative Stress, Inadequate CO2, Dicarbonyls, Depleted Glutathione, or Some Combination?

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,

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,, 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,

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 

Thursday, November 27, 2014

Is a Divide Developing Within the LCHF Camp over the importance of using ketones for energy?

Dr. Michael Eades has argued that the Inuit used ketones as a key energy source on their traditional diet, that the only reason they weren't measured as producing many ketones is that they were "ketoadapted," and that using ketones was a good thing for them, and also a good thing for others to emulate:
"according to most of what I’ve read, the Inuit ate a diet made of about 50 percent caribou, 30 percent fish, 10 percent seal and 10 percent rabbit, polar bear, birds and eggs. These are the figures Stefansson quotes, but they are confirmed by others. Both Stefansson and Murdoch, who wrote the ethnology report for the government in the late 1800s (predating Stefansson) reported that the Inuit ate about the same amount of food, in terms of calories, as a standard American and ate the same amount of fat. I’m not sure I agree, but that’s what they reported. I would think they would have eaten more fat.

... I can tell you from many years of experience treating patients on low-carb diets that you don’t have to eat a 70-80% fat diet to go into ketosis. You can eat steak, chicken, lamb chops, virtually any kind of meat along with a salad and a green vegetable and get nicely into ketosis. And stay there for a good while. Ultimately, if you stick with such a diet, you end up ketoadapted and your level of measurable ketones fall.

He even argued against eating too much protein, so as to avoid slowing down the ketogenic process;
"keep an eye on the protein intake. Too much protein will prevent the shift into ketoses [sic] because the liver will convert some of the protein into glucose – this glucose will then be used first and slow down the ketogenic process.  Which, if course, prompts the question, how much protein is too much?  As long as you’re getting your protein from meat, especially fatty cuts of meat, you’re probably okay.  If you go for the extremely lean cuts of meat, say, skinless chicken breasts, or if you are supplementing your diet with low-fat protein shakes, you could have a little more trouble low-carb adapting."

Peter of the Hyperlipid/high-fat-nutrition blog recently hypothesized that most of the Inuit (and other Artic/subarctic peoples) "did not develop high levels of ketones," due to a genetic mutation:

The P479L gene for CPT-1a and fatty acid oxidation

Peter: "I have some level of discomfort with using the Inuit as poster people for a ketogenic diet. That's fine. They may well have eaten what would be a ketogenic diet for many of us, but they certainly did not develop high levels of ketones when they carried the P479L gene. ...

Ultimately, point scoring on the internet about what the Inuit did or didn't eat shouldn't destroy people's chances of health. Destroying a circular argument about Inuit diets may [make] the destructor feel good. ...."

Dr. Eades does not appear to agree with this hypothesis:

Michael R. Eades, M.D. said...
"@Tim Steele

You wrote: "I'm not sorry I helped topple a faulty core tenant of the modern day Ketogenic Diet."

Pretty hubristic, I would say. I would argue that it hasn't come close to being toppled by you or anyone else."

It will be interesting to see where this debate leads.

Sunday, August 24, 2014

Did You Know That There's Sugar in Your Shrimp and Lobster?

It was shocking enough for many in the Paleo/ancestral and LC communities to learn that there's a super-"safe" starch called resistant starch. When they get around to investigating trehalose, their minds may really be blown! Trehalose (aka "mushroom sugar") is a super-healthy sugar that's found in fungi (such as shiitake, maitake, nameko, and Judas's ear mushrooms), sea algae, honey, and even crustaceans (such as shrimp and lobster) and insects.

As with resistant starch, Paul Jaminet, the "safe-starches" guy, was ahead of the crowd, touching on trehalose back in 2010:

Trehalose may provide some amazing benefits. Physician and anti-aging researcher James Watson reported that trehalose "activates autophagy via an mTOR-independent mechanism." (Autophagy – the housekeeper in every cell that fights aging, Posted on 19 April 2013)

Paleo dieters and Peatarians alike might be interested to learn that trehalose has been found to suppress lipid oxidation, a partiular concern with polyunsaturated fatty acids (PUFAs) that are sensitive to oxidation. Trehalose may also "have a kind of suppressive effect on the development of osteoporosis." (Novel functions and applications of trehalose, Takanobu Higashiyama, Pure Appl. Chem., Vol. 74, No. 7, pp. 1263–1269, 2002.

Diabetics have been reporting that trehalose improves their blood sugar numbers. (JC Spencer, "The Sugar Trehalose is helping Diabetics,"

Trehalose even reduced the symptoms of parkinsonism in mice. (Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation, Neurobiol Dis., 2010,

Out of curiosity, I've been experimenting with a trehalose powder (I know, I know, an "evil processed powder"! ;-) ). Instead of causing my teeth and gums to become coated in gunk, I find it slightly cleans them. It seems to reduce my remaining minor dandruff a bit too, though that's more difficult to tell. I haven't noticed any negative effects. It's a bit pricey, though, so I doubt I'll buy much more of it. Trehalose may at least be another reason to eat mushrooms, crustaceans and honey, and some day maybe even insects.

Sunday, February 02, 2014

WARNING: Serious problems have been reported with very low carb diets

See Spanish Caravan's online comments about this, such as at

Resistant starch seems to be especially important. I recommend reading up on it and the Old Friends Hypothesis.

Wednesday, December 25, 2013

Resistant-Starch-Rich Rhymes

As we saw with Ahem! Avoid Margarine, folk/nursery rhymes can contain good health information. Here are some more examples:

Boxty (quick-fried or oven-baked raw grated potato pancakes that were traditionally popular in the Irish counties of Mayo, Sligo, Donegal, Ulster, Fermanagh, Longford, Leitrim and Cavan) contains some healthy resistant starch, especially if allowed to cool:

Boxty on the griddle,
And Boxty on the pan;
The wee one in the middle
Is for Mary Ann.

Boxty on the griddle,
boxty on the pan,
If you can't bake boxty
sure you'll never get a man.

Boxty on the griddle,
Boxty on the pan,
If you don't eat boxty,
You'll never get a man.

Cold nine-day old pease porridge was a traditional English dish also rich in resistant starch (which, unfortunately, few are willing to eat today):

Pease porridge hot, pease porridge cold,
Pease porridge in the pot, nine days old;
Some like it hot, some like it cold,
Some like it in the pot, nine days old.

Tuesday, June 18, 2013

Full spectrum hormetic therapy

Why wouldn't it make sense to use the full spectrum of hormetic therapies, rather than just one side or the other? For example:

 •  Eating pro-oxidants as well as antioxidants
 •  Gorging as well as fasting
 •  Heat therapy in addition to cold therapy
 •  Minus lens and plus lens therapy for overcoming nearsightedness
 •  Relaxation and high intensity exercise

Presumably both extremes of the spectrum would be practiced intermittently.

Sunday, June 16, 2013

What is Ancestral Nutrition Really About?

The key concept of ancestral ("Paleo"/primal/evolutionary) nutrition is not to avoid foods that you thrive on just because they're on someone's list of "forbidden" foods, it's to eat what you thrive on--the foods your body is best adapted to within the context of your lifestyle, to maximize your overall health and fitness goals. Evidence from the archaeological record and observed hunter-gatherer and horticultural peoples are just clues in helping to form a basic template to start from, not final detailed answers for everyone.

It's not about blind nostalgic emulation for emulation's sake, nor is it about excessive reductionism or refusing to employ lessons from biomimicry because of rigid neomaniac ideology. Here are some terms used by proponents of various flavors of ancestral nutrition that give a sense of the basic overall concept:

> Weston Price: "living in accordance with inherited traditions" and "accumulated wisdom"
> Walter Voegtlin, MD: human ecology
> Boyd Eaton, MD: our ancient genome, biological discordance vs. adaptation, Paleolithic nutrition, evolutionary nutrition
> Loren Cordain, PhD: evolutionary template, Paleolithic nutrition, evolutionary nutrition
> Art DeVany: evolutionary fitness, new evolution diet
> Robb Wolf and Chris Kresser: Paleo template
> Mark Sisson: Primal Blueprint
> Kurt Harris, MD: evolutionary metabolic milieu (EM2)