More importantly, the intestinal flora may develop adaptability to acarbose, which means it may become less effective after prolonged use.You can try berberine, which may be the best alternative, as it regulates the gut microbiota normally with only very small absorbed doses.
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Do we know how much the effectiveness goes down?
If it goes down by say 30% or even 50% something it could still be effective and one could perhaps compensate by upping the those a bit.
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I’ve seen no evidence that the effectiveness of acarbose decreases at all over time. Where is that coming from?
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Inactivation of the antidiabetic drug acarbose by human intestinal microbial-mediated degradation
https://www.nature.com/articles/s42255-023-00796-w
Drugs can be modified or degraded by the gut microbiota, which needs to be considered in personalized therapy. The clinical efficacy of the antidiabetic drug acarbose, an inhibitor of α-glucosidase, varies greatly among individuals for reasons that are largely unknown. Here we identify in the human gut acarbose-degrading bacteria, termed Klebsiella grimontii TD1, whose presence is associated with acarbose resistance in patients. Metagenomic analyses reveal that the abundance of K. grimontii TD1 is higher in patients with a weak response to acarbose and increases over time with acarbose treatment. In male diabetic mice, co-administration of K. grimontii TD1 reduces the hypoglycaemic effect of acarbose. Using induced transcriptome and protein profiling, we further identify an acarbose preferred glucosidase, Apg, in K. grimontii TD1, which can degrade acarbose into small molecules with loss of inhibitor function and is widely distributed in human intestinal microorganisms, especially in Klebsiella . Our results suggest that a comparatively large group of individuals could be at risk of acarbose resistance due to its degradation by intestinal bacteria, which may represent a clinically relevant example of non-antibiotic drug resistance.
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Ah - good find. Thanks for posting! So some questions I have are:
- whether this degradation has an impact on the lifespan extension effects of rapamycin
- Are these microbiota also seen in the mice they do the ITP studies on? (If they are, then perhaps the degradation doesn’t matter, as the mice still lived longer)
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I personally understand that the lifespan of mice is much shorter than that of humans, so it must be very difficult to determine the long-term disturbances in the gut microbiota. Additionally, the human gut is the largest immune organ in our body, with the combined weight of the microbiota in our gut being as much as that of a liver. Furthermore, each person’s microbiota is unique. Therefore, the long-term benefits of taking acarbose for healthy individuals, those whose blood sugar is already healthy, may need to be slowly verified over time.
Acarbose basically disables the enzyme that breaks down certain complex carbs into glucose in your small intestines. For example, sucrose is two sugar molecules bound together, a glucose and a fructose. The enzyme (alpha-glucosidase) sitting on your intestinal villi that is supposed to cleave complex carbs down to glucose has been disabled by Acarbose. So the sucrose goes into your large intestines and gets digested by your gut bacteria.This is the drug which limits the body’s ability to process carbohydrates.
This is why the gut microbiota changes when taking acarbose, but I have always been conservative about whether these changes are beneficial in the long term. Normally, our small intestine should break down carbohydrates, but this step is blocked by acarbose. I think it’s similar to gallbladder removal surgery. Normally, the bile secreted by our liver is stored directly in the gallbladder. After gallbladder removal, the bile secreted by our liver flows continuously into our intestines, stimulating our intestinal wall 24 hours a day. Therefore, many people who have had their gallbladders removed are several times more likely to develop colon cancer than those who have not. At the same time, more bile refluxes into our stomach, stimulating our gastric mucosa, causing intestinal metaplasia of the gastric wall
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Why would you think that? Leftover carbohydrates are digested by gut bacteria if you take Acarbose or not, it is the normal process of digestion. It produces some (or a lot) gas and short-chain fatty acids. If you take Acarbose you do not completely block the digestion of carbohydrates in small intestine. You just add some carbs to be digested by bacteria in large intestine.
SCFAs are generally considered beneficial. They play important roles in various physiological processes, including energy metabolism, immune function, and gut health. They help maintain the integrity of the gut barrier, regulate inflammation, and support the growth of beneficial gut bacteria. Additionally, SCFAs have been associated with various health benefits, such as improved insulin sensitivity, reduced risk of inflammatory diseases, and protection against colon cancer.
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Our intestinal bacteria can produce short-chain fatty acids (SCFAs) themselves, and it is not necessary to take acarbose to produce them. Furthermore, there are several types of SCFAs, for example, Butyric acid can be directly produced by Butyric acid bacteria, Faecalibacterium prausnitzii can produce Propionic acid, and so on.
That is what I said, Acarbose or not, but with Acarbose bacteria have more carbohydrate sources to produce more SCFAs.
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How much carbohydrate absorbtion does acarbose really block?
Metformin also can lower IGF1 slightly and that hasn’t been shown to extend lifespan so I don’t buy the IGF1 theory.
There is so much research on IGF1, its probably one of the top 2 most validated pathways for longevity in addition to mTOR.
So, from my standpoint, the data is pretty conclusive of it having “some effect” in healthspan and lifespan.
But I think you can argue that if started later in life, the impact may be small. But even without a lifespan improvement, the disease burden reduction seems to be more compelling. I mean look at the health profiles of the Laron syndrome dwarfs who never get cancer or diabetes… its hard to argue against (except again, how much benefit you’d get from later life IGF1 reduction vs. life-long reduction, this is an open question).
Anyway - we’ve got lots of threads on IGF1, so not to digress too much in this Acarbose thread.
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I’m pulling out my list of people with idiosyncrasies again. “yeah, he’s a pretty good administrator…but he has an obsession with…“the Little People of Ecuador””
Hope you don’t move into @AnUser territory.
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Yes, I absolutely have a thing for dwarfs that never get cancer or diabetes. I mean how could you not love these people… 
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people with Laron syndrome have a significantly reduced risk of cancer and type 2 diabetes.
]> people with Laron syndrome do not seem to have an increased lifespan compared with their unaffected relatives.
I think this conclusion is likely premature given the small sample size… how can you not live longer if you’re not getting cancer or diabetes? " Among the approximately 100 individuals in this population, there were no reported cases of diabetes and one case of cancer.[29]". wikipedia.
Certainly the healthspan is much longer than unaffected relatives.
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Just had a quick google and pulled up a couple of articles
Blockquote
there were 30 deaths among patients with Laron syndrome: 9 due to age-related diseases (8 due to cardiac disease and 1 to stroke) and 21 were due to non–age-related causes. Patients with Laron syndrome from the Ecuadorian cohort died much more frequently from accidents, alcohol-related causes, and convulsive disorders
Blockquote
and another article/quote suggests that maybe people with Laron syndrome think they are invulnerable and eventually their modern diet is going to catch up with them one day.
Blockquote
Guevara-Aguirre said that in the absence of alarming symptoms or blood tests, it can be difficult to convince his [Laron syndrome] patients, who are prone to obesity, that they need to eat right and exercise.
Valarezo just laughs when he tells her she needs to lose weight, and he frets that a modern diet might eventually overtake the built-in protections of her disease.
“Eventually, it will catch up with you,” he said. “They are pushing the limit.”
Blockquote
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Can imagine that psychological and discrimination effects would confound comparisons?
Perhaps comparing to populations with other forms of dwarfism could help, but then you would have other issues to control for.
Does anyone know if they have done any biological age clock studies in that population?
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Not just cancer and diabetes, but also heart disease and Alzheimer’s… that would be the big four… wow!?
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And in rodents it does extend lifespan
See bold parts below
Unlike others with dwarfism, Laron patients don’t lack growth hormone, but they have a defect in the receptor in the liver that is supposed to bind to the hormone and produce a substance called insulin-like growth factor 1. In Laron, there is no binding and no IGF-1 - and stunted growth as a result. But the absence of IGF-1 may also prevent the uncontrolled growth of cells that turn into cancer, and it creates extra sensitivity to insulin that serves as a shield against diabetes.
Longo duplicated Laron in lab rats. "The mice actually lived 50 percent longer and get a lot less diseases. It’s very clear in the mice. Can it be true for people?'" His lab is testing drugs that would block IGF-1 in people, but the question is whether medicine will work as well as an actual mutation in humans. Longo said it will be at least a decade before they know the answer. Meanwhile, his team is also investigating its theory that Laron may be a defense against heart disease and Alzheimer’s. Preliminary results show that at the very least, the little people don’t have any higher risk of those conditions.
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