A new study on the issue of Metformin and exercise effects:
Paper:
Metformin inhibits mitochondrial respiration.
Lowers brain BDNF levels in the brain.
Acts in the brain similarly to a pesticide leading to cognitive dysfunction and possibly neurodegeneration.
Decreases exercise performance and VO2 max.
No convincing evidence for life extension.
I think you need to relabel your scale.
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No, there is no substitute for metformin for those who need it. Cinnamon, berberine, yadda yadda just donât hack it when it comes to lowering A1c. Every hater of metformin jumps on the slightest negative study. And this is a tiny study and really not very well controlled.
Another mixed report on metformin. Since I donât do high-intensity aerobic exercise I donât care if metformin blunts VO2MAX
It is not fully understood why metformin is a life extender. I personally havenât seen any effect on strength or muscle mass while doing resistance exercises. At my latest check-up, my doctor said I donât need to take metformin anymore as my A1c levels have been consistently good for some time.
Maybe I will quit metformin for a while and see if there is any benefit from not taking it.
I will be looking at my A1c and exercise results.
I would say to those who need metformin: I have been on it for decades and I am in excellent shape for an 81yo male. Personally, I havenât noticed any adverse side effects.
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Of course, adverse effects donât apply to everyone and itâs good that you donât have any, but the risk is still there and the longevity benefits are murky at best.
This new article may be a win for Metformin.
Lactate: the ugly duckling of energy metabolism
PERSPECTIVE | Once thought simply a waste product of glycolysis, an appreciation for #lactate as a universal circulating fuel for mammalian cells is garnering new attention, discuss Josh Rabinowitz (@princeton) & Sven Enerbäck (@uniofgothenburg). #Tbt 
As I have posted before, I tend to sail in whatever way the wind is blowing. Sometimes though it is hard to tell which way the wind is blowing. I recently visited my doctor for my semi-annual check-up. I didnât tell him I had stopped taking metformin for a few weeks before my visit. He looked at my latest lab results and told me I didnât need to take metformin anymore.
Today I decided to take another look at metformin and check out some of the latest papers. From the most recent literature, metformin is well respected around the world.
Sometimes you overlook things and I was surprised to learn of metforminâs anti-cancer potential in addition to its anti-aging potential.
After reading a large number of current papers, only a few are cited here. I decided meh, I donât think there is any reason for me not to take metformin. I had been taking it for many decades and I think I can make the case, for me at least, it has stood me in good stead.
âCurrently, 255 clinical trials concerning the potential use of metformin in cancer treatment are being conducted. There is strong evidence concerning the association between metformin use and decreased pancreatic cancer incidence and increased overall survival in colorectal cancer.â
âUndoubtedly, metformin exerts pleiotropic effects on many metabolic pathways. One of metforminâs most significant potential applications is cancer treatment. Studies using in vitro models focused on metforminâs anti-cancer mechanisms and potential uses produced favorable resultâ
âEpidemiological studies have also shown participants taking metformin to have a reduced risk of prostate cancerâ.
Maybe this is why my PSA scores have always been very low.
âMetformin has been implicated in the promotion and maintenance of a healthy gut microbiome and reduces many age-related degenerative pathologiesâ
https://www.annualreviews.org/doi/abs/10.1146/annurev-pharmtox-051920-093829
âMetformin inhibits the proliferation and invasion of ovarian cancer cells by suppressing TRIM37-induced TRAF2 ubiquitination.â
https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.15524
âMetformin, the first-line oral antidiabetic medicine, has shown great antineoplastic potential in various cancer types, despite an unclear mechanism.â
âIn conclusion, metformin treatment in human type I endometrial carcinoma Ishikawa cells and RL95-2 cells can inhibit proliferation, migration, and invasion, block the cell cycle, and promote apoptosis, demonstrating that metformin is an attractive alternative to cytotoxic chemotherapy in human endometrial cancerâ
Several senolytic drugs, such as bafilomycin and quercetin, were shown to counteract cellular senescence caused by SARS-CoV-2 105. Metformin prevented cellular senescence."
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Youâre certainly making some good arguments. I always thought that the pancreatic cancer protection was just in diabetics, but Iâll read your references carefully.
Iâve taken metformin for many years. Along with rapamycin now. Havenât noticed any effect on my exercise ability, but regardless, I mainly take it for the anti-cancer effect:
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I really donât think it causes a loss of muscle mass. It may take a few more weeks to gain that extra pound of muscle mass. So, would you rather potentially reduce your risk of cancer or take a little more time to add muscle mass?
Peter Attilia stop taking metformin because he was exercising at peak levels and he was worried that he had high lactose levels prior to exercising. Zone 2 training for him meant keeping lactose below 2.0 and he was already at 1.6 due to the Metformin. If lactose is helpful for mitosis then that may a positive for Metformin for people like me that donât exercise at peak levels.
Nir is obviously a huge proponent but he points out that two of the three laboratories in the ITP study showed a positive lifespan increase. But the third didnât and so that was the conclusion. He also argues that mouse studies are irrelevant for metformin because we have so much human data and the human data is more positive. Which is a good point.
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I currently take 500 mg Metformin every other day. One thing I can definitely say is that I will never be constipated again while taking Metformin. Based on the literature, is it better to do a daily dose or take it every other day? Anyone have any leads on this? Thanks in advance!
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I think the best info we have to go on is the design of the TAME Metformin study - and its 1500mg slow release 1X day.
Details here (PDF of a presentation on TAME Study):
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Thatâs a lot! Last time I was on that dosage, I had bad side effects. I think I need to stick to 500 mg either daily or every other day. Is there any advantage to resting a day or longer with metformin?
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In reviewing the studies on metformin, many of the benefits are in diabetics or are attributable to mTOR inhibition which would be redundant in rapamycin users.
I was impressed by this study on ovarian cancer:
https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.15524
In patients with BRCA mutations, metformin might be a good option.
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As far as metformin and prostate cancer, the studies are conflicting with some actually showing an increased risk.
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Very weak study.
"he pointed out that the sample of men taking metformin was too small and there were too few events (99 PCa cases and 62 high-grade PCa cases) âto have enough degrees of freedom relative to the number of covariates included in the multivariable models to make meaningful conclusions about whether metformin use is associated with prostate cancer.â
"Although the authors report that metformin use was associated with a higher risk of any PCa and high-risk PCa, they were unable to account for a possible selection bias, Dr OâNeil said. "
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I thought the benefit of Metformin, if any, was activation of AMPK and improving the function of mitochondria. I havenât seen inhibition of mTOR listed. I think itâs correct to say that it doesnât protect against prostate cancer. That was one of the cancers where it had no effect.
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Metformin and mTOR inhibition
Hereâs another look at metformin, cancer, and mTOR
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.13780
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Thank you! And one more. Matt K. is correct when he describes Metformin as a dirty drug. It affects so many things.
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