Subscribe: Comments on The Daily Lipid: Where Do Most AGEs Come From? O Glycation, How Th...
http://blog.cholesterol-and-health.com/feeds/7531288697775481317/comments/default
Added By: Feedage Forager Feedage Grade B rated
Language:
Tags:
acetone  age  ages  anonymous  chris  diet  don  fructose  glucose  glycation  hba  high  ketogenic diet  methylglyoxal  study 
Rate this Feed
Rate this feedRate this feedRate this feedRate this feedRate this feed
Rate this feed 1 starRate this feed 2 starRate this feed 3 starRate this feed 4 starRate this feed 5 star

Comments (0)

Feed Details and Statistics Feed Statistics
Preview: Comments on The Daily Lipid: Where Do Most AGEs Come From? O Glycation, How Th...

Comments on The Daily Lipid: Where Do Most AGEs Come From? O Glycation, How Thy Name Hast Deceived Me!





Updated: 2018-03-15T12:57:51.679-04:00

 



Hi Russell, I fixed it. Thanks for bringing that ...

2016-05-18T16:11:15.742-04:00

Hi Russell,

I fixed it. Thanks for bringing that to my attention.

Chris



Hi Chris, the links that you give in the first par...

2016-05-13T17:58:58.991-04:00

Hi Chris, the links that you give in the first paragraph of http://blog.cholesterol-and-health.com/2011/10/where-do-most-ages-come-from-o.html
no longer work.
Where can I see your comments/blogs about glycation and AGEs?
Thanks, Russell Eaton



Hi Chris, have you ever heard of a 25(OH)D level o...

2014-02-16T10:34:27.167-05:00

Hi Chris, have you ever heard of a 25(OH)D level of 295? My sister was tested and had this level, the lab retested and came up with the same results. She was tested positive with a MTHFR gene mutation (1298). Was curious what you thought it could be. Thanks!



Hi chris, what do yo think about recent studies sh...

2014-02-15T00:37:18.720-05:00

Hi chris, what do yo think about recent studies showing methylglyoxal reducing anxiety behaviors. Something about GLO1 being oveactive in rats with anxious temperaments and MG being a Gaba A agonist. Would it be foolish to take manuka honey with the intention of getting extra MG to curb anxiousness?
Thanks, kit



Chris, Had you read this post on Hyperlipid befor...

2013-11-05T08:43:21.311-05:00

Chris,

Had you read this post on Hyperlipid before writing this?

http://high-fat-nutrition.blogspot.com/2009/11/methylglyoxal-on-atkins-uh-oh.html

Peter's theory is that methylglyoxal is a potent inhibitor of glycolysis, exactly the kind of thing you want around when you're trying to conserve glucose - e.g. high-fat diets, or serving as substrate inhibition to avoid runaway glycolysis. He cites a review paper looking at the role of oral methylglyoxal in killing highly glycolytic cancer cells.

Any thoughts? Might methylglyoxal be a useful byproduct in our body after all, under normal physiological levels? Thanks!

Will



Hi Chris, I think there is more to the equation th...

2013-02-22T06:43:12.665-05:00

Hi Chris, I think there is more to the equation than the worrying production of methylgyoxal. Something that should please anonymous and a few others of us... The process of autophagy, or cell recycling, starts up at the same time as ketones form or/and blood sugar reaches some low limit. Once dietary proteins have dropped down below a threshold causing BS to production to reduce, this process is likely seeking new fuel. If we look at a BS (?) level above the well known threshold at which "the furniture must go into the fire", cell garbage recycling or autophagy would take place.
New garbage formed by the methylglyoxal in this ketogenic and proteolytic state is likely not longlived since the net effect seems to be recycling and clean up.
See abstract to a study claiming that ketones stimulates CMA here: http://www.ncbi.nlm.nih.gov/pubmed/15883160
Your investigation and comments will be most welcome by many more than me, I guess!



@Chris, Does the first para in your comment of No...

2012-01-08T23:08:07.826-05:00

@Chris,

Does the first para in your comment of November 17, 2011 6:07 AM still stand? If so, could the current wave of fructose-phobia be somewhat overblown?

With thanks,
Mike



Hi Will, Much to my consternation I have failed t...

2011-11-17T09:07:11.167-05:00

Hi Will,

Much to my consternation I have failed to find any evidence that fructose increases glycation in vivo, despite knowing of this argument for a decade or so. As I stated in the article, direct glycation by sugars is not a major pathway for glycation, and this applies to fructose as well as glucose.

The paper you cite is about microorganisms! This is generally assumed for humans also but not very well proven, and likely context-dependent. I listed numerous reasons to expect this might not be or not always be the primary source in this post: that in certain contexts such as diabetes, fasting, caloric restriction, and ketogenic dieting, the threonine and ketone pathways should become more active, and I listed two studies offering some preliminary support for this.

Hope that helps,
Chris



Chris, you don't mention fructose much as a gl...

2011-11-17T03:54:00.670-05:00

Chris, you don't mention fructose much as a glycating agent. My understanding is that glucose preferentially becomes cyclic forms instead of the open-chain form, which is a few orders of magnitude less reactive than fructose. I didn't really believe glucose played a significant role in AGE formation compared to fructose before reading this. Any thoughts?

The Wikipedia article on methylglyoxal cites this study (http://www.ncbi.nlm.nih.gov/pubmed/8540421) claiming the main source is a byproduct of glycolysis. It seems we can avoid that pathway by predominantly burning fat! Is there any reason to believe this is not the primary source?



I'm watching this ^^^ with keen interest... th...

2011-11-07T20:44:27.329-05:00

I'm watching this ^^^ with keen interest... thanks for the great research.. us paleos are very "hungry" to learn ground truth! I love where you're going, even if it kicks my tree so to speak. =)



Of course another possible contributor to the elev...

2011-10-31T04:27:36.300-04:00

Of course another possible contributor to the elevated AGE levels in the vegetarians are all the polyunsaturated fatty acids from cooking with vegetable oils that gets oxidized and converted to dicarbonyls.




2011-10-31T04:25:30.703-04:00

This comment has been removed by the author.



Hi Anonymous, It's possible that methylglyoxa...

2011-10-29T06:04:26.187-04:00

Hi Anonymous,

It's possible that methylglyoxal would have decreased after a certain time, though there was no sign of it in the study, as it seemed to rise for two weeks and then plateau. As I acknowledged before, there are other reasons not to give that study the final word as well. Acetone is not the major ketone. Cells use acetoacetate. But in the blood you have beta-hydroxybutyrate and acetoacetate, and you get a little bit of spontaneous formation of acetone, much of which is given off in the breath or urine, and some of which is converted to methylglyoxal. Sorry for bursting your delusion bubble! But I'm sure it's fun if you learn something. :)

Jet,

That's a possibility, but there are two many other nutritional factors that should affect the result and focusing in on carnosine as an anti-glycation agent as these authors do is sort of myopic. As I outlined here, there are lots of other nutritional factors involved.

Chris



What do you make of this study (Eur J Nutrition 20...

2011-10-15T17:19:38.258-04:00

What do you make of this study (Eur J Nutrition 2001;40:275-281) that found "enhanced plasma AGE levels in vegetarians in comparison to omnivores..."? Could the carnosine in the meat eaten by omnivores be decreasing their AGE levels or could the increased carbohydrate intake in vegetarians be causing an increase in endogenously formed AGE?



I can't find where I got this info from but I ...

2011-10-14T23:01:54.890-04:00

I can't find where I got this info from but I was under the impression it took 40 days for your brain to be as keto-adapted as it could and only need 40g of carbs instead of 120g. Maybe that's bad info but if it's true, six weeks brings you just at the very beginning of this.

But I didn't know acetone could not be recycled without creating AGE-y methylglyoxals. I thought cells just learned how to eat the acetones raw. Ouch. Oh well, at least my brain and heart run more efficiently and the neurosurgeon Jack Kruse thinks ketones might allow use to use 35-100% more of our brains at any given time (from 1% to 1.35-2%)*, and since I'm eating in a small time window I'm giving my cells more time to clean up their organelles. (Doing this in part to see if I can live longer than the normal human lifespan so I don't like AGEs for obvious reasons)

* see:
http://jackkruse.com/do-food-electrons-impart-a-quantum-effect/

Hmmm, health effects of AGEs? Perhaps they are as misunderstood as ketone bodies, uric acid & cholesterol...

"I don't see why it would seem more odd that methylglyoxal can be derived from acetone than it would that it can be derived from glucose or threonine."

Well I do think it's odd. Do you know why? Because I've decided to go on a ketogenic diet (other health conditions practically forced me to anyways), and I have decided that ketones are 100% pure awesomesauce and nothing they do is ever bad. So yes, in that sense it does seem odd - your observations are oxidizing my magic bullet cure and creating all sorts of cognitive dissonance! I challenge your observation on the grounds that it makes me feel slightly sad that ketones don't magically make AGEs disappear and might keep me from living another 120+ years in perfect health. How can you even post such things in you blog? Don't you know people have delusions to maintain?!



Hi Anonymous, In a preliminary study, one subject...

2011-10-14T18:10:47.351-04:00

Hi Anonymous,

In a preliminary study, one subject had his methylglyoxal levels rise after a week on the Atkins diet, reach a maximum at two weeks, and stay plateaued at that maximum for the next six weeks, which should be more than long enough for keto-adaptation. In the main study, the subjects were on the diet for 2-4 weeks, which should also be enough for keto-adaptation.

Acetone is not used as a fuel itself. It is a byproduct of ketone bodies responsible for "ketone breath." In fact the only way to use it for fuel is to convert it to methylglyoxal and then to lactate and then to glucose. Otherwise it is dissipated in the breath or urine.

I don't see why it would seem more odd that methylglyoxal can be derived from acetone than it would that it can be derived from glucose or threonine.

The study had some flaws, as I noted, and they didn't show that the diet could kill anyone faster than any alternative. I haven't gotten to the health effects of dicarbonyls and AGEs yet, but I'll get there. :)

Chris



In those AGE & ketogenic diet studies, did the...

2011-10-14T17:58:01.341-04:00

In those AGE & ketogenic diet studies, did they wait for their patients to become keto-adapted so their mitochondria could burn acetone itself as a fuel source? Or did they make the all too common mistake of just getting people on an extremely carb restricted, high fat diet and then started measuring AGEs without giving them time to adjust?

It seems odd that something our bodies naturally produce when we're sleeping or fasting/starving and when our bodies are repairing itself & clearing out junk instead of digesting food & getting all anabolic, is designed to kill us faster or at least fill our tissues with more junk to clean up...



Responses to Stabby, Anonymous, Pal, and Johnny. ...

2011-10-09T17:06:25.563-04:00

Responses to Stabby, Anonymous, Pal, and Johnny.

Hi Stabby,

Haha, thanks! If you see my previous post on quantifying AGEs, you will see a major problem with all of these "high-AGE" studies -- first, none of them actually quantify AGEs in a reliable manner; and second, they simply show biological effects of high heat-treatment of food, usually with no real evidence that it is mediated by AGEs. Yes, there are other potentially toxic products formed during heating, but there is also loss of glutathione, vitamins, other antioxidants, etc. See here for example:

http://www.westonaprice.org/blogs/cmasterjohn/2010/09/11/the-biochemical-magic-of-raw-milk-and-other-raw-foods-glutathione/

I didn't read the full text, but the abstract of the study you linked to states that creatinine clearance was higher, so they probably had decreased AGEs because of higher renal clearance. They had more inflammation and oxidative stress, so I'm not quite convinced that is a good thing.

Aww Stabby, you da man. :)

Anonymous, you're welcome, and thanks.

Pal, great! That's what I was shooting for. Thanks!

Johnny, yes I did briefly mention that bacteria synthesize it. To my knowledge, there is no way that methylglyoxal can directly produce HbA1c, but methylglyoxal can be used to form glucose, which can produce HbA1c. I have not studied HbA1c extensively, but my understanding is that it is affected by three main factors: 1) RBC turnover, 2) total blood glucose exposure, and 3) fructosamine 3-kinase (F-3K) activity. F-3K is the "chaperone" mentioned above. Glucose interacts with hemoglobin to produce HbA1c consisting primarily of fructosyl-valine and fructosyl-lysine. F-3K reverses this by cleaving the sugar moiety off and converting it to fructose 3-phosphate, leaving behind the normal hemoglobin. When red blood cells are degraded, HbA1c is also eliminated. So perhaps the ketogenic diet is a) affecting RBC turnover, b) decreases F-3K activity, or c) increasing blood glucose. Are you measuring blood glucose? Is fasting or postprandial glucose improving on the diet?

Chris



You wrote: "HbA1c is an example of an "e...

2011-10-09T08:49:15.891-04:00

You wrote: "HbA1c is an example of an "early glycation" product." Does that mean that HbA1c has nothing to do with dicarbonyls, which is "intermediate glycation" products? In clinical practice we have seen in some patients on a very low carb/ketogenic diet that their HbA1c is raising over time (and we have no reason to believe they are cheating, i.e. gorging carbohydrates). Of course we are aware of other possible explanations, but could there be a connection with the formation of methylglyoxal from ketone bodies? Or does methylglyoxal from gut bacteria play a role here?

Johnny



Interesting article. Methylglyoxal is also a metab...

2011-10-09T05:27:00.688-04:00

Interesting article. Methylglyoxal is also a metabolite from gut bacteria affecting signalling mechanisms in cells around the body:

Bacterial metabolic 'toxins': A new mechanism for lactose and food intolerance, and irritable bowel syndrome. Campbell AK, Matthews SB, Vassel N, Cox CD, Naseem R, Chaichi J, Holland IB, Green J, Wann KT. Toxicology. 2010 Sep 18.

Johnny



Great post. Thanks a lot. It actually made sense t...

2011-10-09T05:18:59.539-04:00

Great post. Thanks a lot. It actually made sense to me.



Nice article. Thanks.

2011-10-07T19:41:27.243-04:00

Nice article. Thanks.



Trying to say methylglyoxal-derived hydroimidazolo...

2011-10-07T18:59:49.576-04:00

Trying to say methylglyoxal-derived hydroimidazolone-1 (1) 3 times fast makes me sound a lot like Professor Frink http://www.mclol.com/wp-content/uploads/2010/02/Professor-Frink1.jpg

So I gather that this stuff is, like, complicated. I have seen that "high AGE" diets are bad, at least in the case of diabetes. But perhaps that has to do with non-AGE toxins from high-heat cooking?

I recently found this study http://www.ncbi.nlm.nih.gov/pubmed/18645732 it looks like body fat reduces circulating AGE concentrations. What does this mean, should I pack on a few pounds? Or does it probably not matter and serum AGEs isn't a great assay for health?

Anyway, you da man, Chris. Cheers.