Acarbose with food extends mice lifespan, does Acarbose "without" food also extend mice lifespan?

Acarbose has very low bioavailability, less than 2% gets absorbed as the active drug, and 35% as metabolites, it’s believed that Acarbose extends lifespan by slowing glucose absorption.

But many diabetic drugs can also slow glucose absorption, but they can’t extend lifespan much like Acarbose.
I wonder beside the reduction of postprandial glucose blood concentrations, does Acarbose extend lifespan by other pathways? such as altering the microbiome on GI tract?

I am curious if we treat Acarbose on the fasting mice, can it also has anti-aging effect?
If taking Acarbose on the fasting can also extend lifespan, then it’s a good news that we can take mega dose of Acarbose on the fasting, while avoiding those annoying adverse effects.

Absorption

Acarbose acts locally in the gastrointestinal (GI) tract with low systemic bioavailability (less than 2% gets absorbed as the active drug, and 35% as metabolites).

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Good question… what is the overlap with caloric restriction? It hasn’t been tested, but it would be interesting to find out.

But ultimately maybe the better question is how well it works with other longevity medications because real Caloric Restriction with Optimal Nutrition (reducing caloric intake by 30% to 50% over many years while still getting all the important nutrients that your body needs) is so hard, and so unpleasant (I’ve tried it for a year) that I think the percent of people who could do it and would continue to do it for years, is likely under 1% of people, so its kind of irrelevant.

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This is a great question because I do very low carb most days and I have the same quandary. Can they put mice on a keto diet? Do they ever?

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The confusion arises because acarbose is an mTOR inhibitor, so it may be extending lifespan purely due to that pathway and nothing to do with glycemic control.

There’s also confusion around the SGLT’s because it’s very possible that they act via a klotho pathway, and again, nothing to do with glucose control.

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The more simple explanation sounds more plausible in my opinion. Glucose and insulin are both inflammatory. It seems to me that much about mammalian health links to glucose. The leading causes of death are strongly linked to glucose and the mechanism of so many known ways to improve health do so as well: caloric restriction, time restricted feeding, metformin, exercise, ketogenic diet, etc. What would be different about acarbose mechanism of action? I’m personally doubtful about the benefits of acarbose without food.

citation needed for it being an mTOR inhibitor

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ACA exposure also reduces mTOR signaling in liver and kidney tissues [2, 8]. 17aE2 is a non-feminizing steroid that has a reduced affinity for the classical estrogen receptors

Source: Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation | Immunity & Ageing | Full Text

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Miglitol - Wikipedia gets absorbed - we urgently need ITP on this. Why can’t we just do lower-sample size and much denser analytics?

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Could this be possibly downstream from blunting glucose spikes?

The multiple morbidities are actually secondary to diabetes rather than glucose per se . If it were strictly glucose then very strict glycemic control of diabetics would greatly lower end organ damage and mortality rates. Very major studies have shown that that is actually not the case.

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I thought that the longevity effects of Acarbose were due to gut microbiota changes. The question then would be - are carbs in the diet required for this to happen? Does Acarbose do anything if you’re on a Leto diet?

Unless you are planning to eat lots of carbs or have a diabetic problem already I’d recommend against using Acarbose. It will change your microbiome as certain bugs get starved out when they can’t process glucose anymore. It causes bad gas too. The whole lesson to be learned from Acarbose is to control your glucose spikes as they cause a whole host of damage to your tissues that results in inflammation. I personally eat slow carbs (low glycemic index) with lots of soluble and insoluble fibers (yes, brings on the gas too!). I also tend towards high protein keto as well but I think we are designed for slow carbs. Slow carbs were survival foods just 2000 years ago. Good times you porked on meat, fat, and berries when you could get them. Otherwise to was the tough nasty taters. And they were nasty and tough too.

Its really not understood yet - see here: Acarbose - Details On Another Top Anti-Aging Drug

Rich Miller’s current interpretation of the life extension benefits of acarbose is that it is blocking the very highest levels of glucose. He suggests that in humans, we often look at hemoglobin A1C, which gives you a measure of avg. blood glucose over the last few weeks, and if a person with diabetes takes acarbose, that hemoglobin A1C goes down — signifying that it’s working in a person, but in mice it turns out that HbA1c does not go down. Therefore, he suggests it’s probably not an overall change in the amount of glucose that gets in, but a change in how quickly the glucose enters the blood stream.

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KarlT’s observation finds support in a 2019 paper from Richard Miller et al.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567620/

The more recent paper of Chinese scientists (jULY 11, 2022) cites Miller’s paper, and further states:

The effect of acarbose on intestinal fermentation products may influence its overall effect on host physiology. SCFAs are the main products of starch fermentation of intestinal bacteria, which are beneficial to health, and a positive correlation has been reported between SCFA levels in mice feces and their survival rates [14]. Acarbose could influence both the composition of the bacterial community and SCFA levels in mice feces. Changes in the butyric and acetic acid levels after acarbose treatment vary in different populations from different countries. The acetic acid and butyric acid levels were found to increase after acarbose treatment in most populations in Germany and the United States [33-35], but no significant difference was observed in the butyric acid level after acarbose treatment in diabetic populations in China [36]. In nondiabetic people in the United States, the butyric acid levels increased, whereas the acetic acid levels did not significantly change after acarbose treatment [37]. In feces of centenarians in China, seven characteristic compounds (i.e., total SCFA; manganese; cobalt; and acetic, propionic, butyric, and valeric acids) were identified. This metabolic pattern, particularly the increase in the levels of total bile acids and SCFAs, may have an important and positive effect on longevity [38]. In another study of centenarians in Sardinia, their intestinal microbiota showed potential health promoting characteristics, which was related to the high capacity of glycolysis and SCFA production, leading to the extension of lifespan[39]. For instance, in mice fed with acarbose, the abundance of the SCFA-producing bacteria Lactobacillus increased [40]. Besides their anti-inflammatory effects, SCFAs can also regulate immunity [41]. In addition to well-known SCFAs, such as acetic, butyric, and propionic acids, other SCFAs have the ability to extend the life span. For example, formate can reduce the generation of reactive oxygen species (ROS), which can also extend the life span.

Thus, acarbose affects longevity by influencing the abundance of SCFAs [42].

Michael Lustgarten also has a video on SCFAs and longevity:

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This rings true, and makes more sense than the glucose peak theory. I don’t think glucose peaks could amount to much A1C change for a metabolically healthy person. A1C is a 100-120 day period of average glucose 24 hours a day. A spike lasting an hour 3 times (meals) a day would have to be huge to move the overall average by much.

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Yes, acarbose does not have much effect on the A1C, but it is the glucose spikes AND the triglyceride spikes that do the damage.

Acarbose has other lifespan/healthspan properties in addition to controlling glucose spikes.

I was unaware of the lipid-lowering effects. Some of the effects that I attributed to pantethine may have been due to acarbose. In any case, my lipids have been at an all-time low since I started these two supplements.

I initially was not a big fan of acarbose, mainly because of the effect it had on my digestive tract and the bloating and gassiness it produced.

As RapAdmin pointed out, by reducing or eliminating grains, especially wheat from the diet, most of the bad effects will go away. Since I have switched to a very low-carb diet the side effects have completely gone. Even though my diet alone eliminates any but the most minor glucose spikes after a meal, I still continue to take acarbose because it also eliminates lipid spikes.

This is from one of the best reviews of acarbose that I have come across. It references Meta, Cochrane, and other systematic reviews.

“The beneficial effects of acarbose therapy on serum lipids have been well described. Initial research by Hillebrand et al,81 from a double-blind crossover study, showed that acarbose has a dose–dependent effect for reducing postprandial total triglycerides, with a 200 mg dose being the most effective.”

I think most people taking acarbose are unaware of its lipid-lowering effects.

“There was a 26.8% decrease in mean triglycerides among the acarbose group, compared to 9.2% in the metformin group, and an 8.8% reduction in the placebo group. The LDL-C level increased by 5% in the placebo group, but was reduced by 21.8% with acarbose treatment, and remained unchanged with metformin treatment (p=0.0065 for acarbose vs placebo”

“Acarbose has also been found to improve vascular health and also likely has antiplatelet effects. Lastly, acarbose has been shown to provide euglycemia, partially by increasing GLP-1 levels and blunting postprandial spikes of glucose and lipid levels.”

Euglycemia a noun:

"The condition of having a normal concentration of glucose in the blood; good glycemia regulation; good glycemia.

“Also, these authors showed that acarbose further potentiates the postprandial reduction of ghrelin, thus suppressing appetite”

“Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes”

Review: Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes - PMC.

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That’s quite a list of benefits. It is so long I’m inclined to believe it is a fasting or CR mimetic. Why do glucose spikes cause “damage” if they don’t last very long?

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There are quite a few papers citing the risk of glucose spikes. This is just one.

“glucose monitoring devices have revealed that postprandial spikes of hyperglycemia occur frequently, and may be an important determinant of CVD risk. It is proposed that these short, intermittent bursts of hyperglycemia may have detrimental effects on several organ systems including the vasculature and the hematopoietic system collectively contributing to the state of elevated CVD risk in diabetes.”

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@desertshores This is helpful. Thanks. I still have to research why short term higher glucose causes “higher oxidative stress”? Perhaps it is related to insufficient glutathione common in metabolic illness.

Considering all these beneficial effects of Acarbose, it is very surprising why it’s rarely used by mainstream physicians for any purpose.

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