AGEs — Glycation podcast planning

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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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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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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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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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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Turner seems to be saying that AGE’s from food contribute to the modification of long-lived structural proteins in the body. I did not know this. Is there any source I can read about the mechanism?

They have a lot of information on their website. I’d start there.

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Is this a key part for protein powders (I use plant based ones)? Creatine (edited from “creating”) powder? Anyone know how to screen for better vs worse powders?

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I was surprised by the reference to protein powder. I will follow-up for more details.

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Amazing. Thanks a lot @Joseph_Lavelle

Nice to know. Thanks.

https://www.medrxiv.org/content/10.1101/2023.03.18.23287432v1#:~:text=Type%202%20diabetes%20(T2DM)%20is,in%20adults%20with%20cardiometabolic%20conditions.

Carnosine supplementation decreased blood glucose at 90 minutes (−1.31mmol/L; p=0.02) and 120 minutes (−1.60mmol/L, p=0.02) and total glucose area under the curve (−3.30mmol/L; p=0.04) following an oral glucose tolerance test.

1.6 mmol is more than 27 mg.

https://www.joslin.org/patient-care/diabetes-education/diabetes-learning-center/conversion-table-blood-glucose-monitoring

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Full paper says dosage is 1 gram twice a day. Will try this, and report back.

Did you ever hear back on above Joe?

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No. But I asked Claude. See below:

Let me help explain what we know about protein powder and Advanced Glycation End products (AGEs).

Protein powders can potentially contribute to AGE formation through several mechanisms:

  1. Heat processing: Many protein powders undergo heat treatment during manufacturing, which can promote AGE formation through the Maillard reaction between proteins and sugars.

  2. Storage conditions: When protein powders are stored for long periods, especially in warm conditions, this can gradually lead to AGE formation.

  3. Specific protein sources: Whey protein isolates and concentrates may be more susceptible to AGE formation compared to other protein sources due to their amino acid composition and processing methods.

However, it’s important to note that:

  • The AGE content varies significantly between different protein powder products and brands
  • The impact depends heavily on processing methods and storage conditions
  • Fresh, minimally processed protein powders likely contain fewer AGEs
  • The body’s ability to absorb and be affected by dietary AGEs is still being studied

To minimize AGE exposure from protein powders, you could:

  1. Choose cold-processed or minimally processed protein powders
  2. Store powder in a cool, dry place
  3. Consider plant-based alternatives which may undergo less processing
  4. Check manufacturing dates and avoid expired products
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Author affiliations.

Affiliations

  • 1The Procter & Gamble Company, Mason Business Center, Mason, OH, USA.
  • 2Shanghai Skin Disease Hospital, Shanghai, China.
  • 3Human Phenome Institute, Fudan University, Shanghai, China.
  • 4NMPA Key Laboratory for Monitoring and Evaluation of Cosmetics, Shanghai, China.
  • 5Procter & Gamble International Operations, Singapore Innovation Center, Singapore, Singapore.
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https://www.sciencedirect.com/science/article/pii/S0925443918303296#bb0790

Interestingly, trehalose, which is a low glycemic disaccharide, has been proven to remove neurotoxic protein by activation of autophagy, and may potentiate AGE remediation [[155], [156], [157], [158]]. Alternatively, moderate exercise has been shown to induce autophagy activity [159]. All these strategies may represent non-toxic and low-cost suitable approaches to promote the intracellular clearance of AGEs in order to fight diseases related to glycative stress.

https://academic.oup.com/nutritionreviews/article/80/2/255/6335867

Trehalose, in acute randomized controlled crossover studies, has been shown to reduce blood glucose levels.[44](javascript:;),[45](javascript::wink: Both van Can et al and Maki et al demonstrated that, in overweight adults, consumption of trehalose prior to a test meal led to a lower plasma glucose and attenuated insulin rise when compared with a glucose control.[21](javascript:;),[22](javascript::wink: Longer-term parallel controlled studies also show a benefit, but only in individuals with impaired glucose tolerance. Mizote et al determined that 10 g/d of trehalose compared with sucrose for 12 weeks in individuals with metabolic syndrome resulted in a reduction in the fasting plasma glucose levels, but this was limited to those individuals who had greater trunk fat.[23](javascript::wink: Furthermore, when participants were stratified by body weight, individuals on the higher end of body weight also saw a reduction in waist circumference and systolic blood pressure.[23](javascript::wink:

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