18 replies to this topic

[blood]

Dietary AGES linked to dementia, possibly via suppression of SIRT1.

Full text: http://www.pnas.org/...2/19/1316013111

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Weijing Caia, Jaime Uribarrib, Li Zhua, Xue Chena, Shobha Swamya, Zhengshan Zhaoa, Fabrizio Grosjeana,c, Calogera Simonarod, George A. Kuchelc, Michal Schnaider-Beerie, Mark Woodwardf,g, Gary E. Strikera,b, and Helen Vlassaraa,b


Significance

Suppression of NAD+-dependent sirtuin 1 (SIRT1) is linked to dementia or Alzheimer’s disease (AD) and the metabolic syndrome (MS). Because advanced glycation end products (AGEs) promote MS and neurotoxicity, we conducted studies of C57BL6 mice fed isocaloric diets containing defined AGEs [methyl-glyoxal derivatives (MG)] to determine whether food AGEs promote AD and MS. MG+-fed, but not MG−-fed, mice developed brain SIRT1 deficiency, amyloid-β deposits, cognitive and motor deficits, and MS. These findings were validated in older healthy humans with high baseline circulating MG levels by a time-dependent decline in cognition and insulin sensitivity. The data suggest that food-derived AGEs, an environmental factor, contribute to both AD and MS by causing chronic SIRT1 suppression. Importantly, reduction of food-derived AGEs is feasible and may provide an effective treatment strategy for both these epidemics.


Abstract

Age-associated dementia and Alzheimer’s disease (AD) are currently epidemic. Neither their cause nor connection to the metabolic syndrome (MS) is clear. Suppression of deacetylase survival factor sirtuin 1 (SIRT1), a key host defense, is a central feature of AD. Age-related MS and diabetes are also causally associated with suppressed SIRT1 partly due to oxidant glycotoxins [advanced glycation end products (AGEs)]. Changes in the modern diet include excessive nutrient-bound AGEs, such as neurotoxic methyl-glyoxal derivatives (MG). To determine whether dietary AGEs promote AD, we evaluated WT mice pair-fed three diets throughout life: low-AGE (MG−), MG-supplemented low-AGE (MG+), and regular (Reg) chow. Older MG+-fed mice, similar to old Reg controls, developed MS, increased brain amyloid-β42, deposits of AGEs, gliosis, and cognitive deficits, accompanied by suppressed SIRT1, nicotinamide phosphoribosyltransferase, AGE receptor 1, and PPARγ. These changes were not due to aging or caloric intake, as neither these changes nor the MS were present in age-matched, pair-fed MG− mice. The mouse data were enhanced by significant temporal correlations between high circulating AGEs and impaired cognition, as well as insulin sensitivity in older humans, in whom dietary and serum MG levels strongly and inversely associated with SIRT1 gene expression. The data identify a specific AGE (MG) as a modifiable risk factor for AD and MS, possibly acting via suppressed SIRT1 and other host defenses, to promote chronic oxidant stress and inflammation. Because SIRT1 deficiency in humans is both preventable and reversible by AGE reduction, a therapeutic strategy that includes AGE reduction may offer a new strategy to combat the epidemics of AD and MS.

[niner]

I wish the general public paid more attention to Helen Vlassara. Her lab has convincingly demonstrated the many and various toxicities of dietary AGEs. She's even written a cookbook that shows people how to reduce dietary AGEs without making huge changes in overall diet. The avoidance of dietary AGEs is the real reason that raw food diets are good for you. There's a widespread myth that the benefit of raw diets is due to "living enzymes", but that's nonsense. It's the exogenous AGEs.

[Chupo]

This reminds me of this interesting anecdote by a raw paleo dieter who had her AGE levels measured. It told her she had the AGE levels of a five-year-old! Is that even possible or could it have been a bad reading?

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....les/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

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/carnivorous-zero-carb-approach/i-got-my-age-levels-measured-!-wow/

[blood]

Would whey protein be likely to contain high levels of AGEs?

[APBT]

Would whey protein be likely to contain high levels of AGEs?

These may help elucidate (or confuse )
http://www.ncbi.nlm....les/PMC3704564/

http://www.ncbi.nlm....les/PMC3257625/

http://integratedsup...ucts-in-pr.html

http://www.publish.c...per/CH12442.htm

http://www.longecity...d-whey-protein/

http://www.ironmanma...coming-of-ages/

Edited by APBT, 03 March 2014 - 10:41 PM.

[HaloTeK]

I wish the general public paid more attention to Helen Vlassara. Her lab has convincingly demonstrated the many and various toxicities of dietary AGEs. She's even written a cookbook that shows people how to reduce dietary AGEs without making huge changes in overall diet. The avoidance of dietary AGEs is the real reason that raw food diets are good for you. There's a widespread myth that the benefit of raw diets is due to "living enzymes", but that's nonsense. It's the exogenous AGEs.

I haven't read her site yet but almost everybody I talk to or read thinks endogenous AGEs are more dangerous that exogenous (think fructose and polys <--- which may be even worse than fructose). What is your take on that Niner? Plus a mixed diet with meat seemed to lower serum AGEs because of Carnosine and other nutrients. I'm not so sure a low AGE diet is that important as long as fructose is kept low.

Edited by HaloTeK, 04 March 2014 - 09:25 PM.

[niner]

I wish the general public paid more attention to Helen Vlassara. Her lab has convincingly demonstrated the many and various toxicities of dietary AGEs. She's even written a cookbook that shows people how to reduce dietary AGEs without making huge changes in overall diet. The avoidance of dietary AGEs is the real reason that raw food diets are good for you. There's a widespread myth that the benefit of raw diets is due to "living enzymes", but that's nonsense. It's the exogenous AGEs.

I haven't read her site yet but almost everybody I talk to or read thinks endogenous AGEs are more dangerous that exogenous (think fructose and polys <--- which may be even worse than fructose). What is your take on that Niner? Plus a mixed diet with meat seemed to lower serum AGEs because of Carnosine and other nutrients. I'm not so sure a low AGE diet is that important as long as fructose is kept low.

That's what I used to think. Some of Vlassara's data, where they fed animals high AGE vs LOW age diets (the same diet with different levels of heating applied to them) really changed my mind. The effects are pretty large. Now we have a report of a woman a few posts back who's been raw for 10 years and has the skin autofluorescence of a five year old. That does make you wonder... Although she's low carb now, and it's not clear how long that's been going on. Pretty ugly numbers she racked up on her latest blood test, too. But her fasting glucose of 108 kind of makes the point- she has plenty of sugar in her veins, but low measured AGES in her skin. I went to the raw paleo site where she has a picture, and she looks very good for her age. Unless they just got a bogus result with her, it's pretty interesting.

[HaloTeK]

I wish the general public paid more attention to Helen Vlassara. Her lab has convincingly demonstrated the many and various toxicities of dietary AGEs. She's even written a cookbook that shows people how to reduce dietary AGEs without making huge changes in overall diet. The avoidance of dietary AGEs is the real reason that raw food diets are good for you. There's a widespread myth that the benefit of raw diets is due to "living enzymes", but that's nonsense. It's the exogenous AGEs.

I haven't read her site yet but almost everybody I talk to or read thinks endogenous AGEs are more dangerous that exogenous (think fructose and polys <--- which may be even worse than fructose). What is your take on that Niner? Plus a mixed diet with meat seemed to lower serum AGEs because of Carnosine and other nutrients. I'm not so sure a low AGE diet is that important as long as fructose is kept low.

That's what I used to think. Some of Vlassara's data, where they fed animals high AGE vs LOW age diets (the same diet with different levels of heating applied to them) really changed my mind. The effects are pretty large. Now we have a report of a woman a few posts back who's been raw for 10 years and has the skin autofluorescence of a five year old. That does make you wonder... Although she's low carb now, and it's not clear how long that's been going on. Pretty ugly numbers she racked up on her latest blood test, too. But her fasting glucose of 108 kind of makes the point- she has plenty of sugar in her veins, but low measured AGES in her skin. I went to the raw paleo site where she has a picture, and she looks very good for her age. Unless they just got a bogus result with her, it's pretty interesting.

Here's the thing, are you saying this lady is still raw or now is not because she is low carb?. If anything else health will probably being going down hill. It may take a few years for this to happen. A pure raw diet can't be optimal because at some point we just need more nutrients than the typical raw diet is going to provide. If anything the perfect diet is going to be low in fructose, low in polyunsatures, moderate in monos and fat (like 25-35%) and the rest from carbs. Her fasting glucose is horrible and at some point that probably will harm her AGEs or not.

[blood]

... her fasting glucose of 108 kind of makes the point- she has plenty of sugar in her veins, but low measured AGES in her skin. I went to the raw paleo site where she has a picture, and she looks very good for her age. Unless they just got a bogus result with her, it's pretty interesting.

Her complexion looks incredible for her age (assuming her profile pic accurately reflects her skin condition). But what the hell is she eating? Raw meat?

Edited by blood, 05 March 2014 - 01:45 AM.

[motorcitykid]

Maybe some of the pros of dietary restriction are due not so much to taking in less overall food, but taking in less food that's been cooked.

[niner]

Here's the thing, are you saying this lady is still raw or now is not because she is low carb?. If anything else health will probably being going down hill. It may take a few years for this to happen. A pure raw diet can't be optimal because at some point we just need more nutrients than the typical raw diet is going to provide.

It sounds like she's still raw. Cooking food can make some nutrients more bioavailable, but now we have other options, like mechanically breaking up food in a blender. Cooking was important back when all we had were our teeth and calories were hard to come by. Today, calories are hard to avoid. I don't see why a raw diet would be a problem, nutrient-wise.

Her complexion looks incredible for her age (assuming her profile pic accurately reflects her skin condition). But what the hell is she eating? Raw meat?

Yeah, she looked good. And yes, I think some of these "raw paleo" guys eat raw meat. I like raw fish, if it's prepared right and is good fish. I don't know about other animals, but don't forget that the entire animal kingdom (those that are carnivores, anyway) eats raw animals. We're the only ones that have mastered the deep fryer, as far as I know.

You could be raw and still eat raw dairy, right? And sushi... I could deal with that.

[HaloTeK]

Niner, check this out from the inhuman blog. He used to post on here all the time.
http://inhumanexperi...-comparing.html

Notice how the lowest serum AGEs was a mixed diet (probably because of the anti-glycation nutrients in meat)
The next best diet was vegan. and the worst was the lacto-vegi.

He actually came to the conclusion in other posts that it was probably polyunsaturates that caused the most damage with fructose being the next most damaging. I still that if we eat lower fructose and lower polyunsaturate and do our best to lower the AGEs in cooked meat. that will be the best diet.

[niner]

http://inhumanexperi...-comparing.html

Notice how the lowest serum AGEs was a mixed diet (probably because of the anti-glycation nutrients in meat)
The next best diet was vegan. and the worst was the lacto-vegi.

He actually came to the conclusion in other posts that it was probably polyunsaturates that caused the most damage with fructose being the next most damaging. I still that if we eat lower fructose and lower polyunsaturate and do our best to lower the AGEs in cooked meat. that will be the best diet.

Well, there's the question of how serum AGEs relate to tissue AGEs. It seems like they should be closely correlated, but maybe they aren't? In this recent paper, they say that while fructose is a more potent glycoxidant than glucose in vitro, that's not the case in vivo. Meat eaters would get carnitine and carnosine, and those would presumably help to reduce AGEs. The case of the raw food woman with the skin autofluorescence of a five year old might just be a fluke, but I don't think there's any question that the best way to avoid exogenous AGEs is a raw diet.

[Chupo]

http://inhumanexperi...-comparing.html

Notice how the lowest serum AGEs was a mixed diet (probably because of the anti-glycation nutrients in meat)
The next best diet was vegan. and the worst was the lacto-vegi.

He actually came to the conclusion in other posts that it was probably polyunsaturates that caused the most damage with fructose being the next most damaging. I still that if we eat lower fructose and lower polyunsaturate and do our best to lower the AGEs in cooked meat. that will be the best diet.

Well, there's the question of how serum AGEs relate to tissue AGEs. It seems like they should be closely correlated, but maybe they aren't? In this recent paper, they say that while fructose is a more potent glycoxidant than glucose in vitro, that's not the case in vivo. Meat eaters would get carnitine and carnosine, and those would presumably help to reduce AGEs. The case of the raw food woman with the skin autofluorescence of a five year old might just be a fluke, but I don't think there's any question that the best way to avoid exogenous AGEs is a raw diet.

After reading further on down the the thread, I see the raw paleo woman says she and her brother tested twice with the same results. So, it's probably not a fluke.

Regarding that study you posted "(iii) the activity of defensive enzymes (superoxide dismutase, catalase, glyoxalases, and glutathione reductase) was increased in both glucose- and fructose-stressed yeasts, indicating the development of oxidative/carbonyl stress. Perhaps a slightly elevated BG without substantial spikes is hormetic? Not something I’d strive for but just a thought.

Edited by Chupo, 06 March 2014 - 01:45 PM.

[Adaptogen]

is it necessary to avoid AGEs as much as possible, or are reasonable amounts actually desirable?

Preconditioning with Maillard reaction products improves antioxidant defence leading to increased stress tolerance in cardiac cells.

→ source (external link)

[niner]

is it necessary to avoid AGEs as much as possible, or are reasonable amounts actually desirable?

Interesting paper. I guess it's not surprising that a pro-oxidant would show a hormetic effect at low doses. Exogenous AGEs are so freaking difficult to avoid that I have a suspicion that we're probably getting as much or more than we need even if we take reasonable steps to avoid them. In this paper, they looked at ischemia-reperfusion injury, which is a pretty extreme event. I suppose it's conceivable that if a raw vegan and a SAD eater both had equivalent heart attacks, the SAD eater might do a little better, but the SAD guy is way more likely to have the heart attack in the first place. I think that the epidemiology is on the side of a diet low in exogenous AGEs.

[JohnD60]

That 37 year old woman doesn't look particularly young to me in that myopic profile pic.
I did some research on the florescence scanners referenced. The one mentioned from the neatherlands, and one from the U.S. called Truage scan or Truage max. I am not going to spend all day on it, by they appear to have a very holistic medicine vibe to them. They are both from one product companies. The U.S. company seems primarily focused on selling their AGE reduction products, and has a very non user friendly website, with essentially no useful information. The one from the netherlands 'claims' to be calibrated to skin biopsies, but how useful are AGE skin biopsies? My search indicated that the Truage product was conducting free scans at health fairs across the U.S. in 2013, but they don't appear to be planning the same in 2014, in fact they don't appear to be marketing the product at all in 2014. This is not to say that I think AGE research is not important, I do think it is important, I am just skeptical about these products.

A pure raw diet can't be optimal because at some point we just need more nutrients than the typical raw diet is going to provide

I am completely lost as to why you would think a raw diet would be nutrient difficient.

Edited by JohnD60, 04 April 2014 - 05:02 PM.

[Ben]

Is there any information on what affect reheating food in a microwave has on the AGE content of food? I ask because I store slow cooked, low AGE, meals in the freezer but am wondering if the reheating process would negate the good that cooking in a slow cooker has for dAGE.

[Darryl]

Compare the microwaved vs raw AGE contents for beef, chicken breast, and lamb in this paper:

 

Uribarri, Jaime, et al. "Advanced glycation end products in foods and a practical guide to their reduction in the diet." Journal of the American Dietetic Association 110.6 (2010): 911-916.

 

Fully cooking the meats in the microwave appears to increase carboxymethyllysine content, but not as much as higher temperature cooking methods like broiling or frying. Just microwave reheating precooked meats should produce still less.