Acarbose, An mTORC2 Promoter We Should All Take?

I have it in my cupboard and I keep it in my wallet for when I may be eating more starch and I have not taken an SGLT2 inhibitor, but generally don’t like, acarbose.

Its gotten good results in terms of lifespan improvement from the NIA ITP studies, but the side effects of excessive gas, and sometimes diarrhea are so common as to make this medication less than desirable for me (your results may differ).

But I saw these recent comments to renew my interest in acarbose. Perhaps it might be optimal to take lower doses of acarbose, even if you are already taking SGLT2 inhibitors…

Research has shown that higher mTORC2 activation seems to increase lifespan and healthspan:

Additionally, it was noted that Acarbose can increase mTORC2 activity:

So, perhaps acarbose is something that should be added to our protocols even if we are already taking an SGLT2 inhibitor like canagliflozin or empagliflozin and blood sugar spikes are not an issue at all?

Your thoughts?

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Additional commentary:

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My hunch is that the combination can be useful because:

a) acarbose works on starch that is consumed but SGLT-2 inhibitors also works with glucose/sucrose that is consumed

b) the combination in lower doses could be a good strategy to reduce side effects from taking too much of one type (UTI/fatigue for SGLT-2, and gastrointestinal issues for acarbose). They work via different mechanisms that don’t seem to interact as well.

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And another opinion from a doctor familiar with these compounds (and who takes rapamycin himself):

and another doctor weights in with diet info for a patient of his taking high doses rapamycin, and also 300mg of acarbose:

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Dr. Mert Ergol, also had this to say about SGLT2 Inhibitors for anti-aging:

My philosophy with these agents is not to be married to them but rather to date them–take them intermittently for months at a time, cycle them. There is still so much uncertainty about what they do. Metformin in particular depletes b12 over time, there is a rationale for giving yourself time to re-equilibrate.

Also, I like the idea of taking the sglt2i at night to deplete body glucose, accentuate the overnight fast, declutter the mitochondria, induce starvation autophagy.

Metformin induces secretion of glp1 which works at the brain to control appetite. https://pubmed.ncbi.nlm.nih.gov/30518693/

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Given the long half-life of sglt2i, I wonder if it makes a big difference whether one takes it in the morning or night. My strategy has been to consume it an hour or so prior to my first carb-y or sugar meal of the day (when I’m not on keto). I take 25mg empagliflozin, and assume that a bunch of it will be sticking around during the night and even the day after.

Also isn’t sglt2i only supposed to attenuate higher sugar levels? If one’s sugar levels have stabilized after dinner, how much difference would sglt2i at before sleep really make?

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Yes - good questions. I’m not sure of the answers - I was just posting one doctor’s opinions.

I usually take my empagliflozin just like you - an hour before any meal, in the morning (but typically just eat lunch and dinner). I think you want the peak, or higher blood levels during the time of the day you’re eating your main meals… but I’m not sure what the effect would be if I took it at night. Something to test when I have my CGM on - to see the difference.

Here is the blood level curve below:

41598_2017_2895_Fig6_HTML

Yes - the SGLT2i drugs lower peak blood glucose levels. After reading that doctor’s comments I’m going to try at some point dosing at night and seeing what impact it has on fasting blood glucose levels in the morning. An interesting experiment.

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I’d be very interested to see your results! For the usecase of consuming at night , I also wonder if metformin/berberine would be a better option (ignoring effects on exercise here, or assuming one’s being sedentary around the days of ingestion). Metformin would be explicitly reducing the amount of gluconeogenesis but sglt2i will only prevent reabsorption of any high levels of sugar in the kidney.

did you ever do this experiment for yourself?
also found this interesting in regards to when taking the dose

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Not yet. I need to re-order next week and will try the next time I have it.

What is the usual dose of acarbose taken with 5mg sirolimus?

I don’t calibrate my acarbose dose with my rapamycin dose, in any way at all. I treat it completely separate. I started with 25mg of acarbose with every meal and slowly increased it (if you’re new to acarbose and if you have a diet with significant amounts of wheat-based products, you’lll find the gas/flatulence can be a little overwhelming). As I’ve moved my diet mostly away from wheat based products (towards more rice, lentils, etc.) the flatulence issue has largely resolved and I typically take 100mg with every meal. Some people here take upwards of 200mg with every meal.

We (as a community here) haven’t put nearly as much thought and effort into the acarbose dosing question as we have for the rapamycin dosing question. It is something we should perhaps investigate more and test more.

You may want to read these threads also:

  1. Acarbose - Details On Another Top Anti-Aging Drug
  2. Acarbose - Dosing, Use, and Buying Experiences
  3. Acarbose with food extends mice lifespan, does Acarbose "without" food also extend mice lifespan?
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Given the research showing no statistically significant impact on HbA1c between 50mg and 200mg with food, I would argue that taking just 50mg with carb-dense food is sufficient and very affordable.

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It depends what you think the method of action is, for the Acarbose driven life extension. if you think its just the blood glucose levels & spikes, then you are correct. If you think its potentially other mechanisms, then perhaps you want to try higher dosing.

In the ITP studies they dosed between 400ppm, 1000ppm and 2500ppm compared to dosing between 14ppm and 44ppm for rapamycin (ppm in the food).

For Acarbose:

The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%–11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm.

See: Acarbose - Details On Another Top Anti-Aging Drug

and: Supported Interventions | National Institute on Aging

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By how much did the 400ppm dose increase median and maximum lifespan?

The lowest dose of ACA did not change median survival (0% increase), but significantly (p = 0.03) improved survival at ages greater than the median (Table ​(Table1,1, Figure ​Figure1a).1a). ACA had much more benefit in males, whose median lifespans were increased by the three doses by 11%, 17%, and 16%, respectively, all highly (p < 0.0001) significant (Table ​(Table1,1, Figure ​Figure1b).1b).

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This suggests that, for males at least, even quite low doses can get you significant life extension benefits.

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Have you done the math on the dosing from 400ppm to 2500ppm? (for a 50kg to 70 kg person) (I haven’t - thats why I’m asking). A quick glance seems to suggest that 400ppm equates to about 350mg for a 70kg person.

If someone wants to do it, they could use this Dramamine model that we used earlier:

My calculation shows that the ITP fed the mice a human equivalent dose of about 730mg of Dramamine per day for a 70kg person.

Here is the math:

The ITP used 800ppm in food (see attached photo). And 800ppm is 0.08%. A typical mouse weighs about 0.025kg and eats about 4g of food per day, so 0.08% is 3.2mg of Dramamine for the mouse per day. That is a dose of 3.2mg/0.025kg=128mg/kg. Divide by 12.3 to allometrically scale to humans, to get a human equivalent dose of (128mg/kg)/12.3=10.4mg/kg. So for a 70kg human, that would be 728mg of Dramamine per day.

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OK, please check my math. If this Math is correct (and you could get Acarbose very cheaply) how much would you take, and why?

The ITP did not find any acarbose (ACA) longevity benefit (in terms of median survival) in the 400ppm for the combined pool or females and males, only the 1000 and 2500ppm dosing. However, ACA had much more benefit in males, whose median lifespans were increased by the three doses by 11%, 17%, and 16%, respectively, all highly (p < 0.0001) significant

The ITP has in a series of studies (See Acarbose Details) done Acarbose dosing at 400ppm, 1000ppm and 2500ppm (starting at different ages).

My question is what does that equate to in human dosing… here are my estimates:
Based on the FDA animal to human dosing conversion guide here.

400ppm

The ITP used 400ppm in food. And 800ppm is 0.04%. A typical mouse weighs about 0.025kg and eats about 4g of food per day, so 0.04% is 1.6mg of Acarbose for the mouse per day. That is a dose of 1.6mg/0.025kg=64mg/kg. Divide by 12.3 to allometrically scale to humans, to get a human equivalent dose of (64mg/kg)/12.3=5.2mg/kg. So for a 70kg human, that would be 364mg of Acarbose per day. Assuming it split evenly between 3 meals a day, thats about 120mg/meal.

1000ppm

This is 2.5 times the dose of 400ppm, so multiply by 2.5.
Total Acarbose per day: 910 mg. Assuming it split evenly between 3 meals a day, thats about 300 mg/meal.

2500ppm

This is 2.5 times the dose of 1000ppm, so multiply again by 2.5.
Total Acarbose per day: 2275 mg. Assuming it split evenly between 3 meals a day, thats about 860 mg/meal.

Related:

  1. Why is it possible for mice to take high rapamycin doses daily?
  2. Question on Translating Mouse Results to Humans
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Acarbose is not absorbed though…

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