RapMet
#112
holly molly that is a HUGE dose, no side effects?
I have posted the details of what happens on another thread (second high dose).
Remember I bolster my immune system with an increase in cytosolic acetyl-CoA. That enables my cells to fight invaders without bringing in the WBCs.
There are side effects. The effect on glucose is really interesting. So far I have had one 16mg plus GFJ and two 22mg plus GFG. However, I leave many weeks between dosing.
I do not suggest that others should try what I do without understanding it in the round.
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"According to the American Diabetes Association, drinking red wine — or any alcoholic beverage — ***. Because of this, they recommend checking your blood sugar before you drink, while you drink, and monitoring it for up to 24 hours after drinking.
Who knew? I certainly didn’t.
Now we need to test rapamycin with a glass of wine versus rapamycin and metformin for life extension. 
Pinot noir is generally considered one of the healthiest red wines:
Resveratrol: Pinot noir has high levels of resveratrol, an antioxidant that may help with heart health, brain health, and cholesterol.
Maybe I’ll add it to my stack. Really, IMO moderate wine consumption, i.e one glass a day, will not do any great harm.
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I track the effects of alcohol and take view itbis important to have zero alcohol days and not to drink every day.
Thiago
#116
@Olafurpall @Neo @RapAdmin @DeStrider
Any option about this one?
Dietary glycation compounds – implications for human health
For each adverse health effect considered in this assessment, however, only limited numbers of human, animal and in vitro studies were identified. While studies in humans were often limited due to small cohort size, short study duration, and confounders, experimental studies in animals that allow for controlled exposure to individual glycation compounds provided some evidence for impaired glucose tolerance, insulin resistance, cardiovascular effects and renal injury in response to oral exposure to dicarbonyl compounds, albeit at dose levels by far exceeding estimated human exposures. The overall database was generally inconsistent or inconclusive. Based on this systematic review, the SKLM concludes that there is at present no convincing evidence for a causal association between dietary intake of glycation compounds and adverse health effects.
https://www.tandfonline.com/doi/full/10.1080/10408444.2024.2362985
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This article speaks of dietary AGEs. While they are certainly harmful in their own ways (they can cause inflammation when ingested), that has no direct relevance to glycation and AGE accumulation in the body.
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Beth
#118
Question about timing of taking acarbose…
I know it says take it with the first bite of food, but alas, I often forget to take it.
I’ve wondered if it has any positive effects if I take it at other times, or just skip it at that point?
And, is there a guesstimate on the amount of time leading up to a meal, or post meal that you feel there is still a reasonable window where it might have the intended effect?
Thank you
Also, @DrFraser
Are you saying that it has been proven that there is no direct evidence or that there is no evidence that dietary AGEs result in AGEs in the body? I’ve interviewed scientists who say dietary AGEs do accumulate in the body.
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It’s better to sprinkle acarbose powder on the meal instead of taking it with the first bite. And it will have some effects if you take it in the middle of the meal or the end of the meal even though the effect will probably be a bit delayed that way compared to taking it at the beginning of the meal.
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There is a clear distinction between AGEs created in your body from glycation of your body’s proteins, and AGEs created in foods that you then ingest. AGEs created in your body represent proteins that have become damaged by glucose. That’s damage to your body. AGEs in foods represent proteins in the food that have become damaged not damage to your body. Eating such damaged AGEs doesn’t result in your body’s proteins becoming glycated or in them forming AGE products. It’s much more important to prevent glycation of your own body’s proteins than to reduce intake of AGEs. That said, AGEs that you ingest can cause inflammation and can very indirectly increase AGE formation in your body to a small degree, but that’s a very indirect effect.
As far as dietary AGEs accumulating in the body. I haven’t seen evidence of them doing so, not in tissues at least. Perhaps the scientists are talking about their presence in the blood after ingestion. They do accumulate a bit in the blood but they are excreted by the kidneys so I don’t think there is any long term accumulation going on. Their presence in the blood is harmful however. Dietary AGEs that have reached the blood cause inflammation in various tissues by binding to the AGE receptor and I think that’s a main reason why they are harmful.
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jnorm
#122
I was also wondering this question lately and here’s what ChatGPT had to say about it:
Are glycated amino acids substrates for aaRS?
No, glycated amino acids are generally not suitable substrates for aminoacyl-tRNA synthetases (aaRS). Aminoacyl-tRNA synthetases are highly specific enzymes that recognize and attach the correct amino acid to its corresponding tRNA based on precise structural recognition. Glycation, a non-enzymatic modification where reducing sugars (like glucose) attach to amino acid residues, alters the chemical structure of the amino acid, usually at the amino group or other reactive sites. This change in structure can interfere with the aaRS enzyme’s ability to recognize and bind the glycated amino acid.
In fact, glycated amino acids are often treated as abnormal or damaged forms within cells. Cells have evolved mechanisms to detect and degrade glycated proteins and amino acids to maintain protein quality and function, so even if a glycated amino acid were mischarged onto tRNA, it would likely lead to translational errors and dysfunctional proteins.
In other words, the machinery that synthesizes proteins within our cells does not recognize/utilize glycated amino acids, and so glycated dietary proteins are probably not directly increasing glycation of our endogenous proteins.
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jnorm
#123
Another thing to point out is that added sugar/sucrose (i.e glucose+fructose) is probably much more damaging in the context of glycation than starches or glycogen (which lack fructose).
This is because, in the words of ChatGPT:
Fructose is a better substrate for glycation than glucose. This is because fructose is a more reactive sugar in non-enzymatic glycation, also known as the Maillard reaction, where sugars react with amino groups on proteins, lipids, or nucleic acids. Here’s why fructose is more prone to glycation:
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Higher Reactivity: Fructose has a higher propensity for glycation due to its chemical structure and configuration. It reacts more readily with amino groups on proteins to form advanced glycation end products (AGEs) because it exists in a more reactive open-chain form in solution than glucose.
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Formation of AGEs: Fructose leads to a faster and more extensive production of AGEs compared to glucose. AGEs are compounds that accumulate over time and are associated with aging and chronic diseases. Since fructose is more reactive, it accelerates AGE formation, leading to a higher level of glycation-related damage.
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Physiological Impact: In conditions with elevated fructose, such as in high-fructose diets or metabolic disorders, the increased glycation from fructose can contribute to cellular dysfunction and has been linked to complications in diabetes and cardiovascular disease.
Despite being less abundant in the bloodstream than glucose, fructose’s higher reactivity makes it a significantly better substrate for glycation, leading to potentially harmful biological effects when it accumulates.
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Neo
#125
Baby’s are generally very healthy… and still:
(Top journal, just our a few days ago)
Using an event study design with UK Biobank data comparing adults conceived just before or after rationing ended, we found that early-life rationing reduced diabetes and hypertension risk by about 35% and 20%, respectively
https://www.science.org/doi/10.1126/science.adn5421
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Great point. Yes, fructose is far more glycating than glucose and that is certainly a reason to avoid eating lots of fructose. Moderate amounts of fructose however are unlikely to cause much more glycation than eating glucose. The reason for that is that most of the ingested fructose never makes it into the blood but is taken up by the liver after absorption before having a chance to get into the main blood circulation. Therefore my guess is that fructose ingestion mainly increases glycation in the intestines, portal vein and liver, but much less so in the rest of the body.
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Neo
#127
First glucose is “fructose” here right?
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Yes. Thanks for catching that. I’ve corrected it above.
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TeeDee
#129
Hello, I am also curious about acarbose. 60 y/o male. I don’t eat too many carbs. I did a Homa-IR about a year ago and it was 1.17. Tri/HDL ratio of 1.1, so I am reasonably insulin sensitive, I would think. I recently did get an Rx of acarbose (25mg), mostly to have for the possibility of vacations, eating out, etc. I mostly eat at home. But what is the half-life of acarbose, How long before a meal does one take it for the anti glucose effect. I read there can be bloating side effects, which I had not had on the few times I tried it.
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"The pharmacokinetics of acarbose indicate that it has a half-life of approximately 2 hours in healthy volunteers, as previously mentioned. This short half-life is due to its rapid metabolism and excretion. "
It is to be taken immediately before meals.
The amount of bloating depends on the amount and type of carbs consumed.
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I take 50 mg before carb containing meals. To be honest, I eat a lot of carbs. I do exercise quite a bit and I also have a very physical job, so I don’t feel bad about it, just saying. After about 3-4 weeks, the bloating and flatulence calmed down a lot for me, for what it’s worth.
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