I believe most people would benefit from metformin for all the reasons you just mentioned. Most people do not have healthy practices of adequate sleep, diet / fasting or exercise. If you controlled for that, then it would be interesting what metformin would show. Many of the of this sites members, including @RapAdmin, choose not to use metformin for various reasons one of which is that their healthy habits or other options for sugar control decrease the advantages of metformin.
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This doesn’t say anything about causing damage/cytotoxicity or causing weird molecular irreversible/pro-entropy chemical reactions.
The best reason to take Metformin is that it knocks out many of the negatives of Rapamycin and enhances its strengths. If you are taking Rapamycin, it is almost a no-brainer to take Metformin as well. That’s why I think many top scientists taking Metformin are closet Rapamycin users.
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I agree. I didn’t care about metformin much before, but now I’m taking rapamycin, I now take metformin to counter the sugar/insulin potential side effects. Do you think 500 mg - 1g of metformin a day is enough for a non diabetic rapamycin user? I got no idea what the ideal dose is for non diabetics for the anti aging benefits.
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I scale my usage. I start with 1 g for the first two days after Rapa. Then 3 days at 500 mg. Then 1 day nothing. Then 500 mg the day before dosing Rapamycin. This is all based on my own feelings and intuition. So take it with a grain of Metformin…
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Thanks! i’ll give this dosage regime a try as well.
On the other hand, some scientists/doctors who take Rapa stopped taking Metformin. I find it confusing.
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What was their reasoning? The usual reason to stop Metformin is because it affects their exercise. If so, then it’s your call as to what is more important.
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I’m giving Metformin a try for 1 month. If it improves my markers (at present FG 92, FI 2.5, A1C 5.9), I’ll continue. Muscles maintenance though is very important for aging bodies. I exercise much to support muscle tone. Hope Metformin doesn’t ruin my efforts.
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Here you have another one:
“Metformin and phenformin damaged mitochondria of human platelets at complex I, one of the primary centres of the energy production of the cell. The toxic effect was more pronounced with phenformin than with metformin. But for both drugs it aggravated with increasing dose. Further, we were the first to show that metformin causes the same toxic effect to human white blood cells as it does to human platelets. The damage also was found to be caused at complex I and increased with higher doses. Additionally we showed that with prolonged time of exposure to metformin, as it occurs during treatment conditions, the damaging effect on mitochondria in human platelets increased.”
Mitochondrial toxicity of metformin and phenformin in human peripheral blood cells assessed by high-resolution respirometry | Lund University
I just want to point out that I haven’t said that the damage is irreversible.
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The combination can be good as you say or to use other alternatives such as Berberine, Acarbose or other interventions. What’s your view on that?
By the way, when it comes to longevity leaders. Who is taking both rapamycin and metformin? I know Peter Attia is not taking it. Does for example Alan Green take both?
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In another thread it was mentioned that berberine has side effects that Metformin does not. I believe it was kidney damage related.
Attia doesn’t take Metformin for the exercise reason. I believe Dr. Green does prescribe Metformin.
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do you know if Acarbose has these negative effects also?
Yes, Alan Green prescribe metformin but I’m not sure he takes it himself. If you find some longevity leaders who take that combination let me know 
Really? You are citing a student’s work from 2013.
“Student publication for Master’s degree (two years)”
Quite frankly it puzzles me that in the face of the overwhelming research done on metformin that has not found this before that you would cite a student trying to get a master’s degree in 2013 at a relatively minor university at that.
If you do not want to take metformin, don’t.
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This is not something only one student has said. In a interview where Peter Attia interviews Nir Barzilai in that interview I’m quite sure Nir also mentions this. As I said before it’s nothing bad that something is toxic. There is something called hormesis which means that the body gets stronger by a stress reaction. The important thing here is to just get the dose right. Not too low or not to high. I don’t understand why you get angry on me because of this?
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I am not angry, I just think citing a student’s unpublished, unpeered-reviewed thesis paper from a minor university and “mentions this” from a Youtube interview is not proof or suggestive of anything.
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Ok, I will try to find the podcast where Nir mentions this because he is little bit the good father of metformin these days. I will also see if I can find a pubmed article in the topic. I’m quite sure there exists one. If you stumbled on something let me know. We are here to learn, share knowledge and do this longevity journey together. So lets see what we find in the topic.
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Because I use Berberine I had a quick look at Pubmed, but could not find any particular renal negatives. My own creatinine is just below the normal minimum from my lap so I think my GFR is ok.
How do they even define damage here? I’m not convinced until they do oxidative stress or apoptosis or cfDNA essays. Inhibition of function/overproduction of lactate is not damage.
Therefore, the healthiness of mitochondria of human platelets and white blood cells was assessed by measuring their oxygen consumption in response to exposure to metformin and phenformin
(even carbon monoxide and 2,4-DNP are not mitotoxic at ulta-low doses - both are even hormetic at these doses)
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Here is a good part when Tim Ferris interviewed with Peter Attia:
"I’ve interviewed a guy named Nir Barzilai on my podcast and we’ve talked exclusively about this. He is one of the world’s experts on metformin and he’s leading the charge to do a very large clinical trial to test the question of whether metformin is longevity drug in non diabetics. Anyway, the point is my baseline view was the case and I had been taking metformin since 2010. What changed a year ago was I began doing a very focused type of exercise that geared towards mitochondrial performance and efficiency something called zone 2 training. Where you basically push the boundaries of how much work you can do while keeping lactate below 2 millimolar. So lactate is a byproduct of metabolism under conditions in which you’re asking the body to make ATP which is the energy currency at a rate faster than can be sustained aerobic by using oxygen only. So pushing the boundaries of how much work you can do and I mean work in the very technical sense so how fast you could run, how many watts you could push on a bike and ratcheting up that level while still keeping lactate below you are training your mitochondria to be more and more efficient. What I started noticing when I was mucking around with different drugs was whenever you have metformin in your system that output goes down and when you thought about it for a minute that shouldn’t be surprising it’s a mitochondrial toxin.
This idea of zone 2 efficiency is so important for metabolic health that I started questioning well why the hell would metformin be a good thing if it’s impairing that. And basically after doing a lot of experimenting with and without metformin, metformin under different clearance pathways etc. It becam unambiguous to me that metformin was impairing this and there was no two ways about it. And then I began to question well you know how would you reconsile that with the fact that metformin is helpful and then you realize that metformin has only really even been shown to be helpful in people who have diabetes. And when you look at the sort of mitochondrial performance at people with diabetes it’s abysmal. In fact, even though that’s not a hallmark that the medical system would typically pay much attention to but if you do that type of zone 2 testing in people with diabetes it’s such a contrast between them and someone without diabetes. So I realized well maybe when your mitochondria are that sick a little bit more toxicity doesn’t matter that much. But if you’re playing a differnt game it might. Now since that time a number of studies have come out and I’ve written about one of them, maybe actually two of them, that look at the effect metformin and mitochondrial inhibition on the difficulty of growing muscle mass, which is not as interesting to me but that appears to be a totally different issue which is the blocking of sort of the stress response. I think the jury’s still out on that.
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I think it’s still too soon to soon to say how this story shakes out but I was basically in the past year I’ve seen enough of data to suggest that for me personally the benefits of just focusing and doubling down on my exercise are probably going to yield better results than the use of metformin. And of course then the question is how do you translate that into patients and whre do you draw that line which patients are sufficiently on the healthy enough side. I don’t know the answer, I think my thinking on that is the more you exercise and the healthier you are the less benefit and potentially the more detriment you could experience from metformin."
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Source: Dr. Peter Attia, MD — Fasting, Metformin, Athletic Performance, and More | The Tim Ferriss Show - YouTube
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