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

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#43

Thanks for the ping. Mitochondrial health seems indeed essential to neurological health. See from yesterday: Mitochondrial Transport Key to Neurological Health

I’m still taking acarbose from time to time whenever I have a big meal (most likely on social occasions). However, I’m unsure about its potential for neurodegenerative diseases, and I was (positively) surprised to see the Leigh article when it was published. I’m unsure because, contrary to GLP1RAs and SGLT2is that seem to be associated in longitudinal studies and RCTs with lower risks of depression (a pre-symptom of many NDDs), AD, and PD, acarbose (and other α-glucosidase inhibitors) seems to be “neutral” for these conditions:

Also, most people with NDD have impaired olfactory neurons and acarbose does not seem to help with this whereas GLP1RAs do: Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study 2022

It worked in autonomic failure though so it could help to manage some symptoms of NDDs: Acarbose, an α-Glucosidase Inhibitor, Attenuates Postprandial Hypotension in Autonomic Failure 2007

One caveat to the above: acarbose is mostly used in Asia, so maybe the studies don’t have enough acarbose users in the West or maybe acarbose is more beneficial to Westerners than Asians. I don’t know.

Also, there are two exceptions that found potential neuro benefits:

Let’s see if the Leigh study triggers a renewed interest in acarbose for NDDs, but for now, I would rank it way lower than GLP1RA and SGLT2 for long-term neuroprotection (meaning, in practice, AD and PD).

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#44

Have read the paper but it seems like the bold part is saying something like “reduced risk in women AND people on acarbose that are not on metformin”?

Btw, a big issue with any clinical trial is that they generally only last for a few years… while neurodegeneration and aging occur over decades - so I think they are ONE great way to help inform decisions, but you have to triangulate with other things too in a “Medicine 3.0” way when making decisions for aging (and probably neurodegeneration).

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#45

Sorry, read too quickly, but again, I don’t attach much weight to that particular paper by one person when other people looking at the same database did not reproduce it. I also find it weird that:

Subgroup analyses showed that the reduced risk associated with acarbose was only observed in women (adjusted hazard ratio, 0.783; 95% confidence interval, 0.618-0.992) and in non-users of metformin (adjusted hazard ratio, 0.635; 95% confidence interval, 0.481-0.837). A model comparing different combinations of acarbose, metformin, and pioglitazone suggested that users of all three drugs had the lowest risk of dementia (hazard ratio, 0.406; 95% confidence interval, 0.178-0.925).

So acarbose protects from dementia when taken alone BUT does NOT protect when taken with metformin BUT protects A LOT when taken WITH metformin AND pioglitazone. :thinking: :exploding_head: I would expect acarbose + pioglitazone (without metformin) to work better than the combination of the 3.

And yes, RCTs are not enough for NDDs; that’s why I look at longitudinal data and animal studies (ofc, animal models suck for NDDs) to have some signals. And so far, the signal for acarbose for AD & PD is very weak at best. Whereas the same studies all show a very strong signal for GLP1RAs and SGLTis.

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#46

In 2011, France and Germany banned pioglitazone due to a concomitant risk for bladder cancer.

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#47

Just published: Risk of dementia and Alzheimer’s disease associated with antidiabetics: A Bayesian network meta-analysis

A total of 1,565,245 patients from 16 studies were included. Dementia and AD risks were significantly lower with metformin and sodium glucose co-transporter-2 inhibitors (SGLT2i). Metformin displayed the lowest risk of dementia across diverse antidiabetics, whereas α-glucosidase inhibitors demonstrated the highest risk. SGLT2i exhibited the lowest dementia risk across second-line antidiabetics. Dementia risk was significantly higher with dipeptidyl peptidase-4 inhibitor (DPP4i), metformin, sulfonylureas and thiazolidinediones (TZD) compared to SGLT2i in the elderly (≥ 75 years). Dementia risk associated with metformin was substantially lower, regardless of diabetic complication status or baseline A1C.

(α-glucosidase inhibitors = acarbose, miglitol, voglibose, etc.)

It doesn’t mean that acarbose causes dementia, it could be a reverse causality: maybe large glucose spikes and excursions cause dementia and people with such glycemic profile are prescribed acarbose more (especially in the West) compared to people with a high average glucose but a low variability.

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#48

So Acarbose may not be superior to Metformin when it comes to dementia. Good to know.

I’ll stick with my Metformin and SGLT2I, then.

I don’t want to be a long lived vegetable.

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#49

I feel that I should add to this thread that anyone into recreational flatulence would really enjoy acarbose. It is in a class by itself.

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#50

Yes, teenage boys would probably love the side effects :grin:

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#51

I realise the point here is humor but I’d like to add that I experienced no increased flatulence on acarbose after about a week. I think it must be down to diet and I don’t eat any wheat.

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#52

I frequently take Acarbose with slices of bread and don’t experience any side effects :person_shrugging:

My diet is plant based for years so I have a different gut than most people, though.

#53

Perhaps your baseline of flatulence is already at the maximum?

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#54

Bummer. You are missing out.

#55

Same here. Never had issues with gas from taking ACA. I take 100 before a meal that has carbs (pasta, pizza, sweets etc) and never noticed any bloating.

#56

I think your gut biome adjusts over time. When I first started taking acarbose the side effects didn’t seem worth it. At first, I adjusted my diet, avoiding wheat products because that seemed to exacerbate the problems. After a few months, the side effects went away.

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#57

I used to get a large amount of flatulence with Acarbose, and then I had a colonoscopy. The bowel preparation wipes out most of the micro biome from what I could tell ( hopefully all the bad stuff whilst some good bacteria cling on). Since then, no flatulence at all.
(State of passing stools also normalised from previously rock hard pebbles no matter how much fibre I consumed).
Makes me think those with a poor micro biome might be better off taking the bowel prep medication even if they don’t have a colonoscopy.