#5

I’m interested in this topic but, as far as I have understood, this putative effect is pretty controversial. Several (how many?) studies have suggested an improvement in lifespan, but how many others have refuted that effect? For example, in a podcast a known Italian oncologist, collaborator of the eminent professor Veronesi, cited a study led by him in northern Italy where such effect was not found.

I wonder if there is a valid review article or umbrella review on this interesting aspect.

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#6

This was the poor quality study that started the Metformin excitement but hasn’t stood up the scrutiny. Maybe TAME will tell us something.

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#7

I think the fact that metformin didn’t demonstrate benefit in the ITP trial plus Attia’s general negativity on the drug has played a role in the longevity community.

I respect Attia’s work but he frequently fails to mention that the longevity test failure was in mice. At times he treats the mouse research as if it were research on humans.

I have been taking 850 mg. with my evening meal for about 10 years mostly for longevity but also to push my A1C back from the borderline.

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#8

Assuming Juan Carlos Izpisua Belmonte of Altos Labs is taking it for longevity, why is he taking it (he is very skinny). Would you take it? If not, why not? Attia tends to be very black white so I am less to inclined to follow him blindly.

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#9

I think Attia’s biggest beef with Metformin was how it raised his lactate during exercise. I think he was using lactate as a marker of fitness, and his lactate was high at lower exertion levels (for someone of his perceived fitness level)…he guessed correctly that it was the metformin. So he quit, and he had to explain himself. BTW, I also felt the negative impact of metformin on exercise…it always felt much harder than it should when I took metformin regularly. I also quit taking it except around my rapa dosing.

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#10

https://x.com/EricTopol/status/1834255916067332613

The anti-aging impact of metformin (randomly assigned, with controls) in male monkeys after 40 months of treatment, a pan-omic clock assessment
—~6 year regression of brain aging, with prevention of atrophy and enhanced cognitive ability
—minimal effect on blood sugar
—evidence for multi-organ decelerated aging

https://www.cell.com/cell/abstract/S0092-8674(24)00914-0

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Metformin decelerates aging clock in male monkeys
#11

After criticizing metformin many times, I stand corrected here: this looks very good! (Chinese paper but from top Chinese institutions)

Which dose did they use? What’s the Human Equivalent Dose?

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#12

I remember Attia cited another drawback of metformin, which would affect deleteriously muscle hypertrophy. Barzilai doesn’t deny that but says that strength remained the same in tested human subjects.
A lot of hubbub as it seems to me.

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#13

Not really getting all of that. Skinny has nothing to do with anything. Black and white is appropriate when deciding whether to take a drug.
I don’t take it because I see no reason to take a mitochondrial poison until there is proof that it helps. Not saying it doesn’t help, just that I don’t see enough evidence.

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#14

And the result in the ITP was actually that the metformin treated mice lived about 7% longer than the control group. 7% isn’t nothing. The difference wasn’t statistically significant, but that doesn’t mean it isn’t real, since the ITP is only statistically powered to detect larger differences.

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#15

Metformin video from Fox 3 month ago (5 min):

#16

1500 on going trial on Metformin

Dr. Greg Steinberg Professor of Medicine at McMaster University who has been studying metabolism for long time.

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#17

I recently picked Metformin back up and it’s pairing nicely with Galantamine. Below is my dosing schedule;

Monday-Friday

AM:

500mg Metformin
2mg of Galantamine

PM:

500mg of Metformin
2mg of Galantamine

I do not take on the weekends as I tend to do most of my strength training on weekend mornings.

Here’s a study showing their synergistic effects on sarcopenia.

A combination of metformin and galantamine exhibits synergistic benefits in the treatment of sarcopenia

If I can combat the associated muscle loss of taking Metformin, then yes, I will continue taking it alongside galantamine.

No negative effects associated with either as of now.

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#18

It’s interesting that galantamine, basically a colinergic agent, has such a peculiar sinergy in C. elegans. Let’s wait for more evolved animal models.
I don’t know if metformin may cause muscle loss or just prevent proper hypertrophy with exercise. The latter would sure be detrimental in the case of people with sarcopenia wanting to gain muscle mass back…

#19

Interesting new turns in the metformin discussion. I have no way to be certain (and I am not motivated enough to execute an N=1 Multiple Baseline w/Reversals design) but in my late 70’s, my muscle growth response was as expected when I increased weight training efforts on biceps, triceps, shoulder, and the ankle and calf muscles. Growth in these areas seems as fast as it was with comparable efforts decades ago. I can’t say the same for the quadricep and hamstring groups. I would think the answer might lie in type differences but the calf muscles are generally the same composition as the quads. Dunno.

#20

My take on the human evidence for longevity is mixed, ranging from ~neutral to significantly positive. Moreover, when you look into the distributional statistics of the studies failing to find significance, you see more than a few positive outcomes. Doesn’t this suggest that the decision-rules should account for individual differences? At the least, it seems reasonable to postulate genetic differences as well as individual differences in starting body mass, visceral fat, etc. Placebo effects are a stretch in some of these designs,

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#21

I really apreciate how you push back against the cult of statistical significance, it becomes even less relevant for N=1 studies (which will become more important with time). Stat sig will be replaced by… something else (and AI will help)

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#22

I struggle to think anything less than 15% is meaningful.

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#23

What do you think about canagliflozin then, afaik 14% increase in median survival for male mice only?

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#24

How long you have been on the combo and what positives have you noticed?

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