Great info. I wasn’t even aware of this. Bookmarked the post. Thanks,
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Here is a good article with free text access too. Enjoy 
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I took metformin, 500 mg/daily for decades, mainly for glucose control. I wasn’t pre-diabetic, but I wanted to lower my fasting glucose. In the last two years, I have been on and off of it.
Why? Because there was a big debate on the merits of metformin in this forum and other places. I think the preponderance of the evidence is that metformin has merit other than just lowering glucose levels. I am currently taking 500mg in the evening.
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See this TAME trial overview.
Metformin dose: 1500 mg slow release 1x per day
MP-Justice.pdf (2.9 MB)
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Metformin slow release gave me skin rash. Did anybody have a similar reaction?
I had a higher reading on my A1C after a blood test about 1.5 years ago… I asked my doctor if I could take Metformin for it and he said yes. (I only wanted to take it because of the interviews that I watched from Dr. Sinclair)
The blood tests that I have taken after the Metformin had little change. Maybe because I was a carb addict… I am still taking it…
I have been having some trouble getting a full night of sleep as I wake up after 3-4 hours after going to bed. I started trying to eliminate the variables and Metformin was one of them. I was taking it right before going to bed. I don’t think it interferes with sleep as I woke up after ~4hrs…
But the interesting thing was when I took it in the morning. I played Pickleball a few hours after taking it and I was struggling to catch my breath the entire match. I needed to take breaks between games which I usually do not need. It was like my muscles had a limited amount of oxygen going to them which made me push more than necessary when sprinting around the court. It was hard to recover between points and it seemed that my heartrate would not come down…
In this paper from Nature, Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells, it states " Experiments in isolated hepatocytes demonstrated that high concentrations of metformin inhibited mitochondrial oxygen consumption , through suppressing complex I of the electron transport chain7."
I remember hearing Dr. Sinclair state that if he is going to exercise the next day, he skips taking Metformin. (If I remember correctly).
I never really gave it much thought about it affecting my athletic performance, but I now have a real life experience with it. Guess I will keep taking it in the evening, but a few hours before bed or with dinner.
I just started taking Rapa, so I’m not 100% sure of the combination of molecules… I need to read up on the info earlier in this thread…
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Do we have anything more recent on this?
Paper highlights:
Summary:
Metformin, primarily used for treating type II diabetes, has shown potential in cancer treatment and prevention. It works by:
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Inhibiting mTOR: Through activating ATM, LKB1, and AMPK, it reduces protein synthesis and cell growth.
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Activating p53: Via AMPK, it can halt the cell cycle.
Benefits in Cancer:
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Prevention: Reduces the incidence of various cancers.
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Mortality: Lowers cancer-related death rates.
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Treatment Enhancement: Improves effectiveness of radiotherapy, chemotherapy, and androgen deprivation therapy (ADT).
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Tumor Behavior: May reduce tumor malignancy and movement.
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Recurrence: Decreases the chance of cancer relapse.
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Side Effects Reduction: Mitigates adverse effects of ADT.
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What else you are taking for neuroprotection?
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Metformin, galantamine, simvostatin would be on the list but I think other items in my stack probably confer neuroprotection.
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Metformin interferes with lactic acid???
Any opinions??
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Attia is no doubt a good guy, well meaning but misses a few benefits (IMHO). And is a bit too "STD of care-ish for me. I took Attias advice and crossed metformin off my list of go buy a large stash to add to my antiaging list (bushel basket). And was ignoring the body builders avid use of metformin that they pair with SGLT2, GLP-1, TRT (testosterone therapy), mitocondria boosters, fat mobilizers. Quite an amazing rise from just anabolics and huge testosterone use.
THEN: Alex Kikel et al, [ https://www.youtube.com/results?search_query=alex+kikel+peptides ] in his 200mph whirlwind health talks (along with Hunter Williams/Jay Campbell) the value of metformin blabla. Then I changed my mind on an Alex Kikel comment that metformin rejuvenates the thymus and boosts mitochondria!!! Attia (or someone in the Allopathic world) said metformin suppresses or is toxic to mitochondria and I took it at that.
IMHO the thymus back to 100% is the anti-aging hole grail. I take HGH secretagogs (boosts) Ipamorlan and Tesamorlan first thing AM. Injected peptides to boost thymus function. There is no easy measure of the thymus function. One thymus boosting company’s rep on youtube said measuring immature T cells (??) before and after…
But: Google Search
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- Studies in mice have demonstrated that metformin can alleviate thymus degeneration and improve mitochondrial function.
Also from the body builders: https://www.youtube.com/watch?v=TGlDV1ZpKco
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Ok Just sharing my flipping from once a proponent, then not interested, back to very interested. When I was taking 500mg/AM I had no digestive issues. Some do.
Re lactic acid running higher after intense exercise. #1 this is only after intense exercise, I believe. #2 for some reason very credible health folks don’t consider this a negative. #3 possibly higher lactic acid is just a hormetic that actually is not entirely bad. Yes for some taking metformin does reduce / block muscle growth, for only some. Some health folks cycle metformin on refeeding/growth days and not on work out days. I’d be in the 5-6 days a week camp.
Some wise health coaches advise cycling ALL nutricals, not just peptides and some nootrophics (phenylparacitam, modafinil etc). So Sunday is my no nutricals day. And less on Saturday. Back to a bushel on M-F.
I tip us older folks to grow/keep muscle via the kaatsu.com bands. I’m happy with our two C4’s. Spousal compition (and complaining) got so bad I bought a 2nd C4. LOL
Take care, curt
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@desertshores and I see others are taking metformin in the PM. Any reasoning for not AM and in the PM?
Tnx curt
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It depends on how much metformin you are taking. If you are taking more than 500 mg of metformin, I would divide the dose.
My 500 mg prescription says evening.
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I take mine in the evening as well. When I was taking 1 g, I split the dose between morning and night. I actually switched to Metformin XR which slowly releases metformin throughout the day in order to avoid GI issues. It’s a little more expensive though.
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I had a strange reaction between jardiance and metformin… Might just be a coincidence. I’ll restart tonight with 500mg xr. My cgm does not go below 5…
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Something I don’t see others stating in this thread is metformin helping with asthma.
- Most studies show reduced asthma exacerbations (fewer ER visits and hospitalizations) in people taking metformin.
- Benefits are likely due to anti-inflammatory effects via AMPK activation, not just blood sugar control.
- Animal studies support this too, showing reduced airway inflammation and remodelling.
- GLP-1 agonists may further enhance asthma control when added to metformin.
- SGLT2 inhibitors perform similarly to metformin, while DPP-4 inhibitors may be less helpful or even worsen asthma control.
- No studies in my review showed harm from metformin in asthma patients. Only one showed mixed results and called for more research.
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Does that include sustained release versions?
Vogue and L’Oreal were not on my longevity bingo card. This is why you don’t gamble.
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There are many drugs and supplements that have anti-inflammatory effects via AMP activation, from aspirin to quercetin.
Oddly, after decades of taking metformin, I began having diarrhea after taking it, even in the extended-release form, so I am no longer taking it.
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We’ll see how I go with it.
“The paper also highlights other relevant pathways: inhibition of NF-κB signalling, suppression of vascular smooth muscle cell senescence, reductions in reactive oxygen species and improved lipid handling via PCSK9 modulation. These mechanisms appear to converge on structural benefits – reduced arterial stiffness, slower plaque formation and improved endothelial integrity – all early markers of vascular aging with known links to mortality”
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