Using a geroscience approach to mitochondrial disease, we expose a connection between neurological mitochondrial disorders and the intestinal microbiome
Acarbose suppresses symptoms of mitochondrial disease in a mouse model of Leigh syndrome
The findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.
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:
The Effectiveness of Antidiabetic Drugs in Treating Dementia: A Peek into Pharmacological and Pharmacokinetic Properties 2022: “A nested case–control study by Wium-Andersen et al. found that acarbose was not associated with a lower OR for dementia [18]. A population-based cohort study, using Korean National Health Insurance claims data of new-onset type 2 diabetes patients between 2002 and 2013, found that acarbose monotherapy did not reduce the risk of dementia [48]. Moreover, a retrospective cohort study using the longitudinal reimbursement database of Taiwan’s National Health Insurance (NHI) found that α-glucosidase inhibitor use did not reduce the risk of dementia. The cohort included 15,524 matched pairs of ever- and never-users of acarbose from patients with new-onset type 2 diabetes patients between 1999 and 2006 [49]. These findings suggest that the glucose-lowering effect of antidiabetic drugs is insufficient to exert a beneficial effect on dementia.”
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).
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).
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. 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.
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.
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.
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.
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.