Ketones Inhibit AGE Formation : LC Research/Media Forum : Active Low-Carber Forums

#1 ^

Sun, Jun-01-14, 06:27

RawNut

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Ketones Inhibit AGE Formation

Quote:

Advanced glycation end products (AGEs), which are the final products of glycation, have a major role in diabetic complication and neurodegenerative disorders. The 3-β-hydroxybutyrate (3BHB), a ketone body which is produced by the liver, can be detected in increased concentrations in individuals post fasting and prolonged exercises and in diabetic (type I) patients. In this study, the inhibitory effect of 3BHB on AGEs formation by glucose from the human serum albumin (HSA) was studied at physiological conditions after 35 days of incubation, using physical techniques such as circular dichroism and fluorescence spectroscopy, as well as differential scanning calorimetry (DSC). The fluorescence intensity measurements of glycated HSA by glucose (GHSA) in the presence of 3BHB indicate a decrease in AGEs formation. The DSC deconvolution profile results also confirm the protective role of 3BHB on incubated with glucose by preventing the enthalpy reduction of the HSA tail segment, compared with the deconvolution profile seen for incubated with glucose alone. The concentration of 3BHB used in this study is in accordance with the concentration detected in the body of individuals post fasting and prolonged exercises.

Inhibition of fluorescent advanced glycation end products (AGEs) of human serum albumin upon incubation with 3-β-hydroxybutyrate.

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#2 ^

Sun, Jun-01-14, 07:23

RawNut

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It reminds me of this woman who had her AGE levels checked. They were the level of a five-year-old.

Quote:

Yesterday got my AGE levels measured with a AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands) that works using skin autofluorescence (SAF). It is a pretty new thing, this link is about one study done

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672176/

Some in my family got it measured too. You need to put in your real age, then measure and it will tell you what you biologic age is according to your body's accumulated AGE's. My mom was 54 (real age 61) and my dad had about the same numbers, a little worse. My bro had 23 (real age 21), he has not lived a healthy life until now, but since a month or so he does great, eats and does good stuff. I am proud of him. Now... I was pretty excited what my number will be... I just had labs done last week and my cholesterol was so high and my glucose too

HDL was 119 mg/dl
LDL was 193,3 mg/dl
Triglycerides 43,4 mg/dl

glucose was 108 mg/dl

and I am eating so much fat and I though holey moley I will have so much AGEs in my body....... but.. my biologic age according to the machine was 5...!?

I had the best by far! They were all stunned.. but I figure it is because I eat almost 100% raw for almost 10 years? When I do not cook anything (almost) there will be way less AGEs? Or is it the lifestyle I am doing? The Kruse style? IDK but I am so happy now! You see... I have been warned from some raw food people that eating so much protein and fat and coconut oil will make huge amounts of AGEs in my body and it will be very bad for my health and I will age fast. I did not listen to them and now it seems my diet is just right. Maybe my high glucose levels are not bad at all either, maybe my body have just made some anti freeze to take me safe through the winter

I was not too surprised though to be honest - I really feel like I am 5 yo ;D

I think this is a great testimonial for the raw vegans that fear animal proteins and fat. I have been eating high animal protein for years now..... Maybe the thing I decided to quit fruits etc years ago was not a bad decision

http://www.rawpaleodietforum.com/ca...measured-!-wow/

Raw meat + Ketones = immortality

Last edited by RawNut : Sun, Jun-01-14 at 08:35.

#3 ^

Sun, Jun-01-14, 08:15

mudgie

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According to the dictionary, "Glycation (sometimes called non-enzymatic glycosylation) is the result of typically covalent bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme. All blood sugars are reducing molecules"

So it would stand to reason that AGE's would decrease as sugar molecules become scarce. Why even test this hypothesis?

#4 ^

Sun, Jun-01-14, 08:29

RawNut

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They didn't replace glucose with ketones. They added ketones while keeping glucose constant.

#5 ^

Sun, Jun-01-14, 09:05

Liz53

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Quote:

Originally Posted by mudgie

Why even test this hypothesis?

Because that's good science.

Very interesting article, Raw Nut.

#6 ^

Sun, Jun-01-14, 16:35

teaser

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Ketones keeping glucose from glycating protein doesn't mean that ketones themselves aren't "glycating" the protein themselves, necessarily. If the glucose is marked fluorescently, but the ketones aren't, cross-linkings with ketones wouldn't be measured. I wish they would reserve the term glycate for those times when it actually involves glucose, though.

Quote:

In vitro glycation of brain aminophospholipids by acetoacetate and its inhibition by urea.
Aguilar-Hernández M1, Méndez JD.
Author information
Abstract
Amino groups of amino acids, nucleic acids and lipids can react non-enzymatically with reducing sugars to form unstable Schiff bases that can then undergo the Amadori rearrangement to form irreversible advanced glycation end products (AGEs). Ketoacidosis is a life-threatening complication in patients with untreated diabetes mellitus and it is characterized by increased circulating ketone body concentrations. Recently, the in vitro glycation of hemoglobin by beta-hydroxybutyrate and acetone was described by our laboratory. This study was designed to evaluate the in vitro effect of acetoacetate on brain aminophospholipids at similar concentrations to that observed in ketoacidosis (16.13 mM total ketone bodies). The effect of acetoacetate was compared to that of glucose and the other ketone bodies; beta-hydroxybutyrate and acetone. The antiglycating activity of urea and glycylglycine was also investigated. The incubation of aminophospholipids with acetoacetate results in the formation of a new compound with an absorption peak at 280 nm. When this reaction product was analyzed by thin layer chromatography using an elusion system of methanol:chloroform:acetic acid:water (8:1:1:0.4), the R(f) value obtained (0.24-0.26) was similar to that of the compound formed by aminophospholipids with glucose. In contrast, this reaction product was not detected in those samples containing beta-hydroxybutyrate and acetone. The formation of this new compound was inhibited by urea more effectively than glycylglycine. In conclusion, this study provides the evidence that brain aminophospholipids react with acetoacetate forming AGEs and that this glycating effect of acetoacetate was remarkably decreased by urea, suggesting a protective physiological role for urea in the body as it was previously stated. Finally, this information adds knowledge about the contribution of ketoacidosis in the pathophysiology of diabetic complications, especially in type 1 diabetic patients

Urea protecting from ketone cross-linking is interesting, though--during starvation or a ketogenic diet, uric acid goes up. Sort of makes we wonder about ketone esters, though--a lot of stuff usually goes along with dietary or starvation ketosis that might not if ketones are just added willy-nilly to a higher carb diet.

#7 ^

Sun, Jun-01-14, 18:46

M Levac

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This is a new one. I read about ketones/glycation inside cells a while ago on Mike Eades' blog, but this one says ketones act in the blood directly. That's two ways where ketones act on glycation.

The Mike Eades blog post: http://www.proteinpower.com/drmike/...eans-our-cells/

I have a couple more links about ketones. We used to think ketones was just fuel, but it seems ketones have many roles. Here's one: http://forum.lowcarber.org/showthread.php?t=457819

#8 ^

Sun, Jun-01-14, 19:04

M Levac

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Also, those two ways ketones act on glycation are fundamentally different. Inside cells ketones are signaling molecules (ketones signal other molecules, which then act on glycation), while in the blood they act chemically (I presume). Furthermore, inside cells the action is on existing AGEs, while in the blood it's inhibition of new glycation. Talk about a clean fuel.

#9 ^

Mon, Jun-02-14, 01:02

RawNut

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Quote:

Originally Posted by teaser

What's interesting about this is that over time, the main ketone in circulation becomes BHB as acetoacetate is converted to BHB by muscle cells. This co-coincides with the reduction in uric acid. Is it a co-incidence or does the body know what it's doing?

Quote:

Originally Posted by M Levac

Amen!

#10 ^

Mon, Jun-02-14, 04:46

teaser

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Quote:

And to me, what's interesting about that--is that some of us continue to show high acetoacetate on urine strips deep into ketosis. So what's it mean to people like us? Maybe beta-hydroxybutyrate is protective against acetoacetate "glycation" as well as glucose glycation. Dunno. I'm not particularly worried about it, I doubt it's a problem. Hyperglycemia is common. Unless people start swilling ketone esters like there's no tomorrow, or have diabetic ketoacidosis, comparably high levels of ketones just aren't in the books.

There are studies showing similar effects of ascorbic acid to uric acid in reducing AGE formation--although with the vitamin c, that's for glucose. I wonder if uric acid works for glucose, vitamin c for acetoacetate?

#11 ^

Tue, Jun-03-14, 11:17

rightnow

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I'm a little confused about AGEs.

I heard that the brown spots people often get on the side of their face and hands as they get older are an example of this.

I heard that this 'symptom' indicates the same thing is going on in organs and such, this glycation.

I'm not really sure what it IS though. Does this mean something is frying your tissue into near-caramel?

PJ

#12 ^

Tue, Jun-03-14, 11:50

keith v

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Thats my understanding.
Your body is a slow cooker, it just takes years and years to make caramel

#13 ^

Tue, Jun-03-14, 13:20

M Levac

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Wiki explains it well enough: http://en.wikipedia.org/wiki/Advanc...ion_end-product

Quote:

Specifically, they stem from glycation reaction, which refers to the addition of a carbohydrate to a protein without the involvement of an enzyme.

This means enzymes, lipoproteins and other protein-based molecules can combine with glucose or fructose for example and become non-functional or start to function improperly. Let's say an enzyme's job is to zip through DNA to replicate or manufacture other proteins and enzymes, and this enzyme becomes glycated, it may still be able to zip through DNA, but now we have no idea what protein it will manufacture. Or maybe it can't zip DNA anymore, but it now has new functions that aren't meant to be. Or it just don't work for anything anymore, good or bad.

What this means is that glucose is toxic in any quantity, if there's no glycation inhibitors or no AGEs cleaner, i.e. ketones. It also means glucose is essential, as inhibition and cleaning are obviously evolutionary adaptation to this toxicity. Otherwise, evolutionary adaptation would have found a way to replace glucose or replace the functions it performs. Good news is the quantity of glucose we absolutely need is tiny. That fact is interesting because it confirms glucose is toxic in any quantity: If we don't eat carbs, we still need to inhibit and clean up AGEs, in spite of the tiny amount of glucose circulating in the blood and inside cells.

If I use my paradigm, it further means that dietary carbs are even more toxic in any quantity than endogenous glucose, since eating carbs will stimulate insulin, which will then inhibit ketogenesis thereby reducing the quantity of AGE inhibitors in the blood and reduce the amount of cleaning inside cells, but also put more glucose in the blood and inside cells thereby creating more AGEs to begin with. Double whammy.

As a whole, it makes dietary fat essential for proper cellular functions and overall health, since ketones are made from fat.

Last edited by M Levac : Tue, Jun-03-14 at 13:28.

#14 ^

Tue, Jun-03-14, 13:46

teaser

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Quote:

Liver spots (also known as aged spot, solar lentigo,[1] "Lentigo senilis"[1]:686, "Old age spot,"[2] "Senile freckle"[2]) are blemishes on the skin associated with aging and exposure to ultraviolet radiation from the sun. They range in color from light brown to red or black and are located in areas most often exposed to the sun, particularly the hands, face, shoulders, arms and forehead, and the scalp if bald.

The spots derive their name from the fact that they were once incorrectly believed to be caused by liver problems, but they are physiologically unrelated to the liver, save for a similar color.[3] From the age of 40 onward the skin is less able to regenerate from sun exposure, and liver spots are very common in this age group, particularly in those who spend time in the sun.

In the vast majority of cases, liver spots pose no threat and require no treatment, though they occasionally have been known to obscure the detection of skin cancer. However, despite being a benign condition, liver spots are sometimes considered unsightly and some people choose to have them removed. This can be done by electrosurgery, laser treatment or cryotherapy.

Wanted to follow up on the brown spots and glycation. Wikipedia fails us--mentions sun damage, but not the nature of the damage. Cooking increases glycation reactions, so it makes sense. The sun shouldn't cause glycation in other organs--but impaired ability to replace glycated proteins with age should be system-wide.

#15 ^

Tue, Jun-03-14, 14:44

rightnow

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Found it! This is what I recently read about this:

Quote:

Any rate, if you have a Selenium deficiency, and you don't want to wait until you get cardiomyopathy and drop dead from a heart attack to recognize it, if you look on your hands and you look in the mirror on your face, if you have liver spots or age spots, and I see quite a few from here, you have an early Selenium deficiency. That's called free-radical damage, and fortunately for you, if you recognize that, and you start taking in some colloidal Selenium, in 4 to 6 months it will all go away. You'll reverse back in 4 to 6 months. And when they go away on the outside, they're going away on the inside, in your brain, and your heart, and your liver, and your kidneys.

That was Wallach -- the dead doctors don't lie guy.

I wonder how ongoing selenium deficiency would relate to that.

PJ