#26

Thanks @Ericross2 These are great questions for Dr Turner. I’ll be sharing the questions in advance so I may receive some answers before the podcast comes out. I’ll share the answers here.

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#27

@Joseph Thanks for the suggestion. I’ll reach out to Dr Vlassara. I was able to find an email address.

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#28

I’m interested in the carnosine question as well, and what percentage of carnosine survives intact (vs. broken down into its component amino acids). I have read some small percentage of exogenous carnosine can survive.

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#29

Here’s the CML database you already have but I just happened upon it and thought I’d put it in the thread. I’m going through it now to see where I can reduce my intake.

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#30

Yes, at least intracellularly.

I doubt it. These building blocks for the ECM mainly support synthesis of new ECM. They don’t really support removal of damage or prevent glycation damage from occurring so I think their effects would be minimal at best. I’m not aware of any research showing that glycine/collagen/Chondroitin sulfate reduce glycation damage and wouldn’t expect them to do so, at least not directly.

Some of it is caused by loss of elastin or damaged elastin. Some caused by cross-linking of collagen or elastin or other ECM components. Btw, UV damage can accelerate AGE formation in the skin. I’m not aware of any topical agents that have good evidence of reversing glycation of skin.

I second that! Vlassara is the name that comes up in my mind when thinking about dietary AGEs. I have been reading her papers since 15 years ago. She has published a lot on the subject and is definitely one of the biggest experts on the subject.

The proportion that is broken down is somewhat individual and depends largely on the activity of your carnosinase enzyme in the blood.

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#31

Here’s the glycation episode. My introduction droned on a bit as I was anxious to get the message out. There isn’t much to learn here on supplements. The solution is in lifestyle: food cooking methods and exercise. But there is a solution. It matters.

The questions asked have not been answered yet but are promised to come soon. I’ll post here.

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Akkermansia mucciniphila improves healthspan and lifespan in old female mice
Acarbose for healthy person? WHY?
#32

Very easy to listen to and enjoyable as always. I find these experts almost the opposite of Sandra Kaufmann. She eats donuts and takes drugs and supplements like candy. They pretty much go for eating things raw or slow cooked and avoiding sugar. I’m doing both at once.

I really feel like an idiot for not knowing all these things when I was younger. I know it doesn’t matter so much, but still I’m nearing retirement age and have painful joints and a CAC of 290 and just think I should have started a little sooner. Oh, well good job putting it out there !!

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#33

Doesn’t coffee have exogenous AGEs, and yet remains pro-longevity?

Is taurine, metformin, or carnosine (or the combination) more effective at preventing AGEs from doing damage? Should they be consumed with AGE-heavy meals?

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#34

Vegetables have AGEs also. AGEs are unavoidable but you can minimize them via diet selection, especially in cooking methods. I’ve read a lot about ways to dodge AGEs (Dr Kaufmann has a huge list), but Dr Turner says nothing is proven to work in people, and certain methods (binders) may backfire. He says the best path is food/cooking method choice and exercise.

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#35

Thanks! I feel the same. I am now avoiding AGEs as much as possible. Fortunately I was already dodging AGEs for the most part by skipping fried foods and grilled meats. It’s a bummer that there aren’t “silver bullet” solutions to let us eat whatever we want but when did silver bullets ever work? Exercise is the only other solution…good enough.

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#36

Oh, and didn’t he make a crack about how glycated dog food is? Or did I hear that somewhere else? I wonder if irradiating and extreme cooking of dog food shortens their lives.

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#37

Yes he did. “Kibble” he called it, so I’m guessing he means the hard, dry food. He says it shortens dogs lives…he does not feed his dog(s) “kibble”.

#38

I must have misunderstood something here: there are AGEs in food, and they aren’t generally good. But the AGEs I am most concerned about are those that are created inside our bodies, such as glucose/AGEs crosslinked into epithelial and elastin proteins/tissues particularly in blood vessels (which reduces cardiovascular health/function, or kidney health/function. Did I misunderstand something? — Isn’t that what we are primarily trying to avoid when we discuss AGEs, and not the exogenous AGEs we consume (which may be important, but not AS important)?

#39

According to the Anti-AGEs Foundation, there is little that can be done to stop the formation of AGEs in our bodies. It is a byproduct of energy production. Our bodies have defense mechanisms built in to deal with it but the defenses can be overwhelmed. Being metabolically unhealthy (over eating, insulin resistance, etc) leads to problems, so avoid or address that as possible. Exercise is good to avoid accumulating AGEs but it’s good for everything. The one thing everyone can do to reduce the accumulation of AGEs is to not eat them.

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#40

I had thought that carnosine (and beta alanine) supplementation helps prevent formation of AGEs (I had originally incorrectly thought that they reduced already-created AGEs but it seems they simply prevent formation). Carnosine is the one you really want, but one turns into the other and these different forms address different organs/body parts. That was the thesis for taking them, no?

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#41

I tried to get Dr Turner to say what supplements might help. He would not. He says nothing has been proven to work in humans, and certain approaches (binding) can lead to bigger problems. I asked about Glylo (ALA, vit b1, vit b6, etc). Dr Turner said that it was a bad idea to resort to unproven strategies. He says we can do a lot with diet and exercise, and that is the only ways known to work.

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#42

Thank you but that’s disappointing, although there are a number of papers suggesting carnosine and beta alanine each prevent AGEs (in different systems). I’ve linked below the thread where we discussed this in detail (the link is specifically where you — @Joseph_Lavelle — corrected my misconception that they reduce already formed AGEs).

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#43

My learning continues. I was and am confident there isn’t a safe way to unmake AGEs. Based on what I have learned since that post, I now speculate that any supplement based improvements in reducing formation of AGEs is a result of improving metabolic health. If you have good metabolic health then no benefit. If you have poor metabolic health, then solve that big problem to solve many problems accelerating aging. Exercise, stress mgmt, reduce glycemic load, fiber, food order. These are my efforts to improve my own metabolic health.

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#44

This is why I think a lot about keeping blood glucose low, I think that’s the only way to reliably slow down the formation. Hopefully acarbose helps here. I also try to walk, or at least be on my feet after meals. Don’t eat and then sit down.

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#45

Here are some AGEs questions answered by Dr Turner. Post more while I have his attention.

Q: Post podcast, a disbelief that no supplements will help avoid absorption of AGEs or formation of AGEs dominated the discussion. Any thoughts?

A: It is possible that supplements may help absorb AGEs but there is no evidence to support that in vivo (in the body). It is more likely for example that antioxidant supplements reduce oxidative stress leading to reduced AGE formation as GlyLo/VitB/benfotiamine etc. are suggesting, but again this has not been shown definitively in vivo. What happens outside the body by no means reflects what happens inside the body. The experiments need to be done to show this. While only a hypothesis it is possible that AGEs can bind to supplements and then act as ligand to RAGE to increase oxidative stress, who knows?

It is very important to note that much of the increase in AGEs is due to the consumption of preformed AGEs in food. GlyLo and all the other supplements cannot help clear these from the body unless they enhance the proteolytic clearance systems in the body that clear AGEs.

Q: Also, any connection between AGEs and endotoxin (LPS) binding to LDL but not being cleared so getting into endothelium and being attacked by immune system (plaque formation)? No connection but similar mechanism?

A: Not my area this one but AGEs have been shown to reduce liposaccharide uptake by cells to impact chemokine secretion. The data basically supports that AGEs can cause aberrant LPS function in cells.

Q: You could ask about what happens when LDL is glycated and can’t be docked on the liver and recycled.

A: While not directly assessed in the liver, publications have shown that AGEs may cause LDL modifications associated with atherogenesis

Q: Is strengthening the ECM with for instance with glycine/collagen/Chondroitin sulfate (or other agents) possibly a preventive measure?

A: Ages actually love collagen and when AGEs attach to collagen it results in a stiffening of the extracellular matrix which is associated with multiple chronic conditions. For example, tumor cells can be more motile of stiffer matrix.

Q: Is benfotiamine of any value?
A: See answer to first question

Q: What can actually be done about AGEs?
I’ll start: take acarbose with every meal, and also metformin on the days when not building muscle. What else can be done?

A: Again, much of the increase in AGEs is due to the consumption of preformed AGEs in food. While acarbose may reduce AGE formation in the body which may help it has no effect on consumed AGEs. The simple message is reduce the intake of AGEs. This may be significant to athletes as lots of the powdered supplements taken by athletes are high in AGEs.

Q: Has AGE formation actually been reversed in any live organism? I’m not talking about just slowing down the problem accumulation.

A: Very astute. This is what I have been talking about above. We know of no way to reverse AGE formation so preformed AGEs in diet is a significant issue

Q: Do Glycans have anything to do with Glycation?

A: Glycans are formed through similar chemical reactions but glycans require an enzyme for their reactions and AGEs do not. Apart from that they do not seem to overlap

Q: I’d love to hear if exogenous carnosine (or beta-alanine precursor) really does have a positive impact on AGEs.

A: In test tubes, these compounds have been shown to have an effect and effects have been shown in animal models but the available data can be very conflicting. The effects in humans have not been looked at in detail and what information that is available does not allow a conclusion to be made. Need more research.

Q: As a follow up, does it make sense for diabetics to be taking carnosine (and/or beta-alanine)? Does it make sense for both Type-1 and Type-2 diabetics? — it seems AGEs are a massive, massive health and longevity issue for diabetics (this is, I believe, what kills them early through stiffening and blocking blood vessels in kidneys, eyes, appendages, etc) and there is zero guidance on what to do to combat the not are there medications to remedy this.

A: Out of all the natural products, the data for carnosine as a diabetes therapy is compelling. However, I am not in a position to say it should be used as a usual care treatment

Q: My understanding is the inelasticity of skin as we age are due to cross linked collagen: is some of this due to AGE instead of UV damage? If it does have an AGE component, is there some topical remedy to use?

A: AGEs love collagen and others long lived proteins in the skin. Yes they do contribute to crosslinking, increased AGEs in tissues correlates with increasing chronological age as well accumulated tissue damage associated with growing older.

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