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
和：Supported Interventions | National Institute on Aging
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By how much did the 400ppm dose increase median and maximum lifespan?
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:
- Why is it possible for mice to take high rapamycin doses daily?
- Question on Translating Mouse Results to Humans
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Acarbose is not absorbed though…
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True, but there is still a dose response. We just don’t know why…
But - it does seem like the benefit maxes out around the 1000ppm, so perhaps thats the ideal intestinal concentration for this drug. There is no added benefit at 2500ppm over the 1000ppm.
more benefit in males, whose median lifespans were increased by the three doses by 11%, 17%, and 16%,
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KarlT
#22
Am I the only one that thinks this is a bit odd. SGLT2’s work in the kidneys which have decreased activity at night. An SGLT2 isn’t going to deplete body glucose, and I don’t know what it means to declutter a mitochondria?
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For an average person, taking a SGLT2 inhibitor at night would have an addictive effect on natural circadian rhythm and functions- that’s the hypothesis anyway.
SGLT2 will not “deplete” glucose but yes, the drug will perform functions regulate glucose over night. I can’t think of why it wouldn’t, but regardless it’s proven to do so- day or night.
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KarlT
#24
Its mechanism of action would be less active at night I would think.
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LukeMV
#25
Morning vs night study on Jardiance here
Results: T max increased by 35% in the evening phase compared to the morning phase, while C maxdecreased by -6.5% in the evening dose compared to the morning dose. Additionally, AUC 0 to ∞increased in the evening phase by 8.25% compared to the morning phase. The mean cumulative amount of glucose excreted (UGE ( 0-24)) increased by 43% in the evening dose compared to the morning dose
Conclusion: Despite the difference in pharmacokinetics parameters between evening and morning doses, C max, AUC 0-t, AUC 0-∞, didn’t differ on the bioequivalence level. In addition, as UGE ( 0-24) didn’t statistically differ, thus, we can conclude that there is no statistical significance between the morning and evening doses.
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Biologically speaking, their cannot be a meaningful difference. I don’t mean this personally, but if you do not have a background in molecular biology this can all be difficult to understand, but this website has a group of people with these backgrounds- myself inc. that you can learn from. I have learned so much, we’re lucky to have such a strong forum.
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KarlT
#27
I was able to pick up a little biology during medical school.
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KarlT
#28
Great article with interesting results. I guess long 1/2 life has significant impact.
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Isn’t this what we really care about , the amount of glucose exerted? I mean you could argue that we don’t really care about the “Cmax”, or “Tmax” or AUC in this case - its the results that matter; glucose excreted?
Of course, if the benefits we seek are coming from something other than just blood glucose reduction (which increasingly seems likely given the plethora of beneficial effects of SLT2 inhibitors), you want all of these. But at least if you take it at night you can feel comfortable knowing that " C max, AUC 0-t, AUC 0-∞, didn’t differ on the bioequivalence level."
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DrM
#30
Before starting a Carnivore diet, I was taking acarbose, but it caused terrible gas. I’m curious about the effects of acarbose on my pure Keto diet. Are there any benefits beyond blocking carbohydrate absorption?
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I experienced the same thing when I first started taking acarbose and even stopped taking it because of the gas etc.
Then I went on a low-carb diet and started retaking it because I had ordered a year’s supply from India on hand and believed it might have other beneficial effects.
Of course, there was a little gassiness even with low-carb meals, but I had less than I had before. I was only taking it if the meal wasn’t low-carb, so I didn’t take it for every meal.
After a while, I noticed when I took acarbose with a high-carb meal, even ones that had a wheat content that I had little or no gas from the acarbose. I am not taking probiotics.
My theory is that over time, acarbose changed my gut microbiome.
So, it would be interesting to know if anyone else had the same experience; that acarbose changes your gut microbiome, and your body adjusts to it.
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Just to add on to DesertShores’ comment - I too had unbelievable gas when I first started Acarbose. Over time and with a shift in my diet away from wheat products, my gas has gone down to a minimal level (still more than normal, but not at a bothersome level). I take acarbose with every meal.
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I went from turning my room into a gas chamber to not noticing anything within weeks.
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