The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose1,2, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases3, limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.
But micro-biome resistance is not really the same as the body developing a resistance to acarbose (and your statement that therefore it has diminishing effects). I have not noticed any diminishing effects in my year of acarbose use (periodically) with regard to blood sugar peak rise. But will continue to watch for it.
Anyone else notice anything related to possible acarbose “resistance” in your use of it?
What matters is the bottom line. Does it extend lifespan? Do you think the mice trials were long enough to see the effects of changing their gut microbiome?
In the NIA ITP trials the compound (rapamycin, acarbose, etc.) is typically included in the food, I believe. So they get it as a proportion of their food (e.g. 44 parts per million of drug to total amount of food).
We tested two doses of acarbose in two distinct diet backgrounds, the HS diet which mimics a low-fat Western-style diet comprised of host-accessible processed corn starch and the PP diet replete with plant polysaccharides and natural fiber sources that include resistant starch. The low dose of acarbose, tested only in the HS background, did not result in a significant change in the community structure from that of the control diet lacking acarbose. However, the high-acarbose diet changed the community in the HS diet background with a massive increase in the Bacteroidaceae and the Bifidobacteriaceae , which in both cases, was largely attributed to increases in single OTUs. There was a nearly concomitant decrease in the abundances of both the Verrucomicrobiaceae , mainly, A. muciniphila , and the Bacteroidales S24-7 with the high acarbose in the HS background. Acarbose elicited different changes when administered in a PP diet, most notably, a jump in the Lachnospiraceae from 10% to 30% of the community with acarbose, and a striking decrease in Bacteroidales S24-7. For both diets with acarbose, the abundances of Bifidobacteriaceae and Bacteroidales S24-7 were quite similar. Acarbose administration enhanced Bifidobacteriaceae representation in both cases, whereas it decreased S24-7 in both diets.
So… does acarbose produce stronger results in amylose/amylopectin or sucrose? Are its differential peak-glucose-lowering effects on high-sucrose food almost as important as its effects on high-amylose food?
Sucrase exists to break down sucrose - does acarbose even work on high-sucrose foods like mangoes?
Acarbose is a competitive inhibitor of intestinal alpha-glucosidases with maximum specific inhibitory activity against sucrase. Under the influence of Acarbose, the digestion of starch and sucrose into absorbable monosaccharides in the small intestine is dose-dependently delayed
But does acarbose even WORK on high-raffinose foods?
RFOs produce flatulence in humans
71 and animals due to the lack of an α-galactosidase enzyme
Do you take acarbose? If so, you tell us. You can take your acarbose then eat the beans you like and tell us the glucose spike you observe.
If you don’t take, acarbose then perhaps someone else on the forum can do the experiment.
It comes in three dosings: 25mg, 50mg and 100mg. You take the medication with the first bite of the meal (generally a higher starch meal, but there is debate on this).
You want to chew the tablet, not just swallow it, for best results. I found 50mg and 100mg to be effective, I’d skip the 25mg tablet size.
Some people take 200mg (as Bryon Johnson does), and I’ve heard some people take 300mg. Monitor your blood glucose levels after eating (ideally with a CGM, but finger prick method also fine) to see how your body reacts to the acarbose.
Is there any evidence that acarbose lowers baseline (e.g. fasting) blood glucose? Or only helpful for lower postprandial spikes / AUC?
I know it lowers HbA1c in some trials, but that could be entirely due to lowering PPBG, not necessarily baseline.
I’ve read through this entire thread (134 posts as of this writing) and just wanted to make sure I understand this (likely simple) concept: acarbose seems only useful if someone eat carbs? or are there other mechanisms? — I personally have been “keto” for 1.75 years and lost significant weight, all my blood/health metrics have improved and are mostly great, have gained muscle, do both weights and 100 flights of stairs most days, and feel f@&$%#Ing terrific and youthful energy (I’m 52) so I’m unlikely to change near term. (By “keto” I mean very low carb but with lots of vegetables and healthy meats and other protein, plus 18-hour fasts 1.5 meal a day “intermittent fasting”, and every six weeks or so I do a four-day water/coffee/tea fasts.) i studied it for six months to psyche myself up to change this in my lifestyle forever, and needed to convince my team of doctors to allow me to do it as I have one kidney (eGFR 89 a few weeks ago so I think the one is working pretty damn well at 52). I understand “keto”/low-carb doesn’t have the clinical trials for longevity behind it, and some of the top researchers suggest low protein content and also plant protein, but I’d rather have a solid layer of lean muscle everywhere so as I age beyond my 50s I have freedom of movement and energy, and it is very anti-cancer.
I don’t use supplements generally but added GlyNAC recently (3g glycine in my morning coffee with 50g NACET), and take 4000 units of vitamin D, although from a recent research paper showing no difference between minoxidil and rosemary I’ve just started trying a rosemary water spray for the beginnings of male pattern baldness over six months — I’ll update the group in a post either way, but no results likely for 3-4 months at least. I’m on this site because I plan to try Rapamycin both topically and orally (I’m considering pulsed every two weeks perhaps as high eventually as 2g every two weeks, on 2 months, off 1 months) but I need to psyche myself up and make sure I’m doing the right thing for my health. I’m of the belief less interventions should be more, because drug side effects can be worse than the benefits. I’m also considering trying carnivore during the “off” months to build even more muscle/bone density (I understand this is unpopular here but it seems to work well for me).
Oh: I should mention I have a masters in Chemistry and worked in a fellowship for a biochem lab for three years (DNA replication proteins) and work occasionally with biotech companies, although its not my daily focus. My point is I read the research directly to make my conclusions, and greatly appreciate this community for highlighting new research I haven’t seen.
Anyway, I apologize for the ridiculously long one-sentence question, but would be interested in anything that could meaningfully impact my health, and it sounds like acarbose could be that IF I wasn’t low carb. Thanks.
We don’t know with any certainty the method of actions for Acarbose with regard to the longevity effect. We have the hypothesis from Richard Miller at U. Penn/NIA ITP that its the lower post prandial glucose levels (from carbs) but that is a theory, see also the thread on Canagliflozin: Canagliflozin - Another Top Anti-aging Drug
If the longevity effect is due to lower post prandial BG levels then it seems to suggest that Keto practitioners would get no additional benefit, but actual mouse clinical studies confirming this have not, to my knowledge, been done.
I’m not a chemist, and not a doctor, just an interested “tech guy” so take my comments with a grain of salt, I can only refer you to some sources. I recommend you also read these threads:
Increased Butyrate and other SCFA’s after fiber fermentation in lower intestine, protects against leaky gut etc? The might be the key longevity point of Acarbose? I only speculate, but I have a gut feeling about this.
I agree with Goran, this is known and important. I’m keto and I take it whenever I’m eating veggies or anything with starch at all. It works and with low carb you don’t need much and it doesn’t have the bad side effects either.
I read here somewhere that it boosts MTOR 2, but was busy and didn’t read the studies and can’t remember where that info came from. If true that could be why it works so well with Rapa.
So if your “gut” feeling is that acarbose increases butyrate in our intestines and that provides the longevity benefit, couldn’t we just take butyrate supplements, or probiotic/prebiotic fiber, or even better: butter (as a source of butyrate) instead of acarbose? I’m always of the belief that fewer supplements/drugs are better (fewer side effects and interactions). I know we don’t have a butyrate clinical trial so the “proof” is missing. Not trying to argue, but I want to simplify my life/“stack”. As a keto practitioner, I’m not sure I’ll require the carb reduction function (yes I know low carb/keto doesn’t seem popular on this site and little longevity research behind it, but insulin resistance, low glucose spikes, lower inflammation markers, weight control, muscle building, and anti-cancer seem worth it to me to “bio hack” this practice, and what a lot of the longevity drugs try to provide). But the acarbose longevity data is compelling.
Just important to keep on mind, with claims like the above, what you’re comparing keto to. The typical American diet of processed junk food? That’s an easy target. Comparing the usual keto diet to a whole foods, plant based diet with adequate protein, on the other hand, is much more of a challenge.