Jasmine2 Posted November 30, 2016 Report Share Posted November 30, 2016 (edited) I've been a long-time lurker here and have probably read through just about every post on this forum. I've been LCHF, even ZC, for many years due to IR and a strong FH of T2 but Rhonda Patrick's videos, especially with Longo, have set me off towards a more plant-based diet. I've just read Ray Cronise and David Sinclair's latest paper, which again reinforces my growing belief that a plant-based is probably more beneficial for healthspan. Anyway I would like to know anyone's thoughts please on Acarbose for longevity; this is such an under-rated and under-used medication for T2's, it seems not only to outperform Metformin but improves lipids, vascular health, blood pressure, weight loss etc. I had no idea as to the full extent of it's method of actions until I found this paper. The side effects of this med seem to be minimal, apart from some early gastro issues. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620230/ Edited November 30, 2016 by Jasmine2 Quote Link to comment Share on other sites More sharing options...
Alex K Chen Posted June 4, 2020 Report Share Posted June 4, 2020 Quote It is used clinically to prevent post- prandial hyperglycemia200 and generally causes weight loss and improved glycaemic control199. Acarbose can rescue age- related glucose intolerance in rats201 and has been considered as a potential mimetic of DR202. In the ITP (Box 4), acarbose increased the median lifespan in male mice by 22%, with only a small effect in females (5%), but the maximum lifespan was significantly increased in both sexes (females 9%, males 11%). Body weight was reduced (more so in females than in males), fasting blood glucose levels and IGF1 levels in plasma were lower in both sexes, and fasting insulin levels were lower only in males. Acarbose increased the healthspan in mice, with reductions in lung tumours in males, liver degeneration in both sexes, glomerulosclerosis in females, blood glucose response to refeeding in males, and improved rotarod performance in ageing females203. In male mice, acarbose also reduced post- mortem liver degeneration, lipidosis202 and hypothalamic inflammation204, and abolished male- specific insulin insensitivity and glucose intolerance205, all of which potentially contributed to the greater effect of the drug on male lifespan, which, interestingly, was abolished by castration205. Acarbose- treated mice showed alterations in the composition and fermentation products of their microbiome and in the composition of the short- chain fatty acids in the gut, although these effects differed between the three ITP test sites206. It is likely that acarbose and DR increase lifespan by partly different mechanisms, given that DR reduced the levels of circulating FGF21 and increased activity levels, whereas acarbose had the opposite effects on these phenotypes202. In summary, although acarbose has some undesirable, although not dangerous, digestive side effects207, there are ample reasons to evaluate this small molecule in the clinic as it may be among the most efficacious geroprotectors identified to date. Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted June 6, 2020 Report Share Posted June 6, 2020 When I got my doctor to prescribe metformin for me, I discussed acarbose with her at length, partially based on the various mice studies. In her experience acarbose is generally very well tolerated and much a more popular drug outside of the U.S. (she also did research and practiced in Europe and Argentina). However, she was cautious wrt. translating the mice studies to humans. In particular, she noted that it's critical to establish what your glucose metabolism looks like - if you are prone to post-prandial spikes, it might be very useful, but if not, then you are getting all the side effects with probably little in the way of benefits. This is one of the issues with translating from animals to humans. As happens my post-prandial blood sugar is excellent, and I don't experience anything even close to spikes. After careful consideration, we decided to forego acarbose and stick with metformin. YMMV. Quote Link to comment Share on other sites More sharing options...
Ron Put Posted June 6, 2020 Report Share Posted June 6, 2020 44 minutes ago, TomBAvoider said: When I got my doctor to prescribe metformin for me, I discussed acarbose with her at length, partially based on the various mice studies. In her experience acarbose is generally very well tolerated and much a more popular drug outside of the U.S. (she also did research and practiced in Europe and Argentina). However, she was cautious wrt. translating the mice studies to humans. In particular, she noted that it's critical to establish what your glucose metabolism looks like - if you are prone to post-prandial spikes, it might be very useful, but if not, then you are getting all the side effects with probably little in the way of benefits. This is one of the issues with translating from animals to humans. As happens my post-prandial blood sugar is excellent, and I don't experience anything even close to spikes. After careful consideration, we decided to forego acarbose and stick with metformin. YMMV. Tom, I am still curious why you and your doctor chose metformin over acarbose, since irrespective of the post-prandial spike control, it appears to have the other notable benefits, such as lowering IGF-1 (let's assume that this is beneficial for longevity, although if I recall, it may increase the chances of dementia, among other things)? I am basing the question on this passage from the paper linked by Jasmine2: "t is difficult to explain the increase in longevity as these mice were not diabetic and were not at risk of developing diabetes. It was discovered that acarbose therapy in mice led to a significant rise in the levels of serum FGF21 and a significant decline in serum insulin-like growth factor-1 (IGF-1) levels.142 It has been established that systemic IGF-1 activity mediates the ageing process and influences longevity in mice.143 Also, FGF 21 by decreasing IGF-1 production decreases the sensitivity of the liver to growth hormone.144–146 Moreover, genetically altered mice with constitutive FGF21 secretion have been reported to have increase in both mean and maximal lifespan, thought to be mediated by IGF-1 downregulation.147 148"On a different, but somewhat related note: I was looking at my glucose results from last year (85) and also insulin results (2.5) and calculated the HOMA-IR, which turned out to be 0.5. I have no idea if the ratio is a good predictor of anything, but it seems to be on the good side as far as I can tell. Does anyone know if having reasonable good insulin resistance makes one less likely to experience spikes, or are the two unrelated? Also, while searching, I came upon this sort of puzzler:Insulin Resistance and Aging: A Cause or a Protective Response? Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted June 6, 2020 Report Share Posted June 6, 2020 Metformin impacts mitochondria (complex 1), acarbose does not (I don't think?). Therefore for longevity, I see more potential with metformin. IGF-1 - totally agree wrt. importance for longevity... but it's super complicated. For awhile there, it looked very straighforward - the dwarves from Latin America were intriguing for health resilience, diabetes avoidance etc... BUT still they were not beating longevity records. Mice appear pretty different from humans when it comes to IGF-1 - unfortunately... and yet again. IGF-1 is at present too unclear to rely on - it appears that in humans IGF-1 is more complicated in its functions (compared to mice). Note this puzzling fact - most CRONIES have elevated IGF-1 (most, not all) - with excellent biomarkers otherwise... why? Regarding that puzzler (insulin resistance) - I have long since suspected that we are too simplistic in attempting to intervene in aging biology, precisely because of the fact that what may seem pro-aging is actually the body's protective reaction. Examples are endless - remember when telomeres were all the rage? If shortening is the issue, why not prolong them - but then it was descovered that when you did that, you got cancer. And so on for tons of things - some hormone levels fall with age, so people supplemented and got cancer or other diseases. The problem is that people think of aging as simple "wear and tear" deterioration, like a car, parts go bad, so if you fix them, you're good to go. But that's not how the body works - the body is INTERACTIVE where there is action and re-action, the body isn't simply deteriorating - it's also fighting to repair itself. Therefore, if you simply try to return all biomarkers, say hormone levels as an example, to youthful levels, you are not actually fixing anything, you might be UNDOING the protective action, the repair the body is doing by lowering some of those hormones - and when you elevate them, you get disaster. It's complicated... just as IGF-1 is. To conquer aging in humans will take an extremely complex intervention - simplistic measures may do more harm than good. YMMV. Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted June 6, 2020 Report Share Posted June 6, 2020 12 hours ago, TomBAvoider said: Note this puzzling fact - most CRONIES have elevated IGF-1 (most, not all) - with excellent biomarkers otherwise... why? Evidence? This appeared to be true in one of Luigi Fontana's early study of some of us [1], but that appeared to be mediated by the relatively high protein diets many of us were eating at the time and subsequently discontinued. I'm not aware of more recent evidence that most CR folks have elevated IGF-1. I for one do not. --Dean ----- [1] Aging Cell. 2008 Oct;7(5):681-7. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Abstract Reduced function mutations in the insulin/IGF‐I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF‐1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long‐term effects of CR with adequate nutrition on circulating IGF‐1 levels in humans are unknown. Here we report data from two long‐term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF‐1 and IGF‐1 : IGFBP‐3 ratio levels in humans. In contrast, total and free IGF‐1 concentrations were significantly lower in moderately protein‐restricted individuals. Reducing protein intake from an average of 1.67 g kg−1 of body weight per day to 0.95 g kg−1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF‐1 from 194 ng mL−1 to 152 ng mL−1. These findings demonstrate that, unlike in rodents, long‐term severe CR does not reduce serum IGF‐1 concentration and IGF‐1 : IGFBP‐3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF‐1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti‐aging dietary interventions. PubMed PMID: 18843793; PubMed Central PMCID: PMC2673798. Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted June 6, 2020 Report Share Posted June 6, 2020 Indeed it was mostly from the Fontana study and this part: "These findings demonstrate that, unlike in rodents, long‐term severe CR does not reduce serum IGF‐1 concentration and IGF‐1 : IGFBP‐3 ratio in humans.", however, yes, I should've mentioned that it's probably mediated by protein intake to some degree. Nonetheless there is still some residual difference between rodents and humans in this respect, which is why, yet again, caution is advised when translating findings across species. The findings that low IGF-1 in very old age might be detrimental has me also cautious. Possibly mice are not long-lived enough to exhibit these issues at advanced ages? Certain pathologies, such as dementia or sarcopenia might not have time to develop naturally in mice - of course one can engineer genetic mice that exhibit this or that, but I always worry that such engineered mice have all sorts of other issues which might make the observed effect not a clear cut case. Quote Link to comment Share on other sites More sharing options...
Saul Posted June 6, 2020 Report Share Posted June 6, 2020 Michael Rae has very low IGF1. the last that I can recall, he was concerned that maybe it was too low. None of us really know. But, Luigi's tests suggest that CR with somewhat reduced protein may be ideal. (Of course, the sample is small -- and no one in the sample has been followed long enough -- only after CRONnies begin dying, will we have any real information on longevity. I'm not in a hurry. 😉 -- Saul Quote Link to comment Share on other sites More sharing options...
Alex K Chen Posted June 12, 2020 Report Share Posted June 12, 2020 Does acarbose work even when you're not taking carbs at the same time? Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted June 12, 2020 Report Share Posted June 12, 2020 55 minutes ago, InquilineKea said: Does acarbose work even when you're not taking carbs at the same time? Acarbose blocks the digestion of starch. If you aren't eating starch it probably isn't doing much. Call me crazy but it seems silly to me to consume more starch than one wants to digest and then take a drug to impair ones natural digestive processes. Although I also think increasingly popular bariatric surgeries for weight loss are a terrible idea. Quote Link to comment Share on other sites More sharing options...
Alex K Chen Posted June 13, 2020 Report Share Posted June 13, 2020 I heard it also has effects on fat digestion too Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted June 13, 2020 Report Share Posted June 13, 2020 4 hours ago, InquilineKea said: I heard it also has effects on fat digestion too I doubt it. It can lower triglyceride levels but people who cut carbohydrate intake such as going on a ketogenic diet also lower triglyceride levels despite massively increasing fat intake. Quote Link to comment Share on other sites More sharing options...
Fernando Gabriel Posted July 15, 2020 Report Share Posted July 15, 2020 If I am not diabetic and take acarbose it will hurt me Quote Link to comment Share on other sites More sharing options...
Alex K Chen Posted November 13, 2022 Report Share Posted November 13, 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190416/ https://www.rapamycin.news/t/alex-k-chen-metabolic-progress-my-aggregate-everything-in-longevity-thread/466/192 Quote Link to comment Share on other sites More sharing options...
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