#21

A new video on Metformin

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#22

This guy is turning out to be more and more like a click bait wh$re, ridiculous head line. But sure people will watch this and they will buy the supplement’s he gets commission on. His Rapamycin trial will never happen, not even close to raising the amount needed. Will he pay back the money raised? or do they disappear in document and consulting fees?
Sorry to sound negative, but I have just about had it with all of the youtube personalities in this anti aging space.
His next video is probably another David Sinclair bashing video, that will get clicks for sure.

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#24

Lolz at the authoritative tone.

What you’ll hear most genuine experts say is, ‘we don’t know…’

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#25

We have research that suggests that metformin significantly reduces the aerobic adaptations to exercise. We have data that suggests a strong correlation between VO2 max and longevity. We have data that aerobic exercise improves metabolic health and blood sugar control…

So, if you’re not diabetic, you’d probably be better throwing your metformin in the bin and going for a bike ride.

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#26

Nice video.
No value for metformin in the non diabetic.
No life extension.
Blunts the positives of exercise on VO2 max.

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#27

Rapamycin gives you diabetic like symptoms that is termed Rapamycin Diabetes. Metformin or acarbose treats that.

The ITP did the studies on Rapamycin and metformin as well as Rapamycin and acarbose and longevity improved significantly in both cases. If we are taking Rapamycin based on the ITP, why aren’t we taking metformin or acarbose with it? It’s the same source.

If you are not taking rapamycin and are not diabetic, then you probably shouldn’t take metformin. I am assuming everyone here is taking Rapamycin or is considering it. Metformin or acarbose should be part of that consideration.

Honestly though, acarbose is probably the better choice vs metformin. Metformin does have negative effects on exercise that acarbose doesn’t.

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#28

I am borrowing the ITPs authority. :wink:

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#29

I’m not a big fan of metformin, just because the mouse data is not impressive and the exercise-related issues.

But the combined metformin/rapamycin ITP study did have somewhat positive results.

See: Rapamycin and Metformin Show Synergy in Mice | Lifespan.io

和：

Metformin alone or with rapamycin (Met or Met/Rapa)

Beginning at 9 months of age, groups of male and female mice began consuming a diet containing 1000 ppm (0.1%) Met. As shown in Figure 2 and Table 1, Met led to a 7% increase in median lifespan of males when data were pooled across sites, but the effect was not statistically significant (P = 0.35). Males treated with Met had site‐specific changes of 13%, −1%, and 10% at the three test sites, but none of these was statistically significant (Table S1, Supporting information; see Fig. S4, Supporting information for the site‐specific survival curves). There was no effect of Met on survival of female mice, either in the pooled data (Table 1, Fig. 3), or at any site (Table S1, Fig. S4, Supporting information).

See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013015/

和：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892694/

However, other experts (Christine Glorioso, who runs the SF Longevity / Global Longevity group and is well versed in the research) has this to say:

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#30

Fuck testosterone, women and eunuchs live longer than men for a reason.

I’m still taking the thing.

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#32

See the video at 2:08. “No significant difference between metformin and placebo”

“Metformin didn’t provide any benefit for these individuals”

No, the first does not imply the other, that is highly misleading. It just means it couldn’t be measured.

I haven’t looked at Metformin in detail, but this type of reasoning is similarly used against statins, etc.

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1 Like
#33

A recent series on metformin

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#34

Dr. David Sinclair is a big fan of Metformin. There have been many tests that show the benefits of Metformin as a live extender. In fact one trial showed that Diabetics that took Metiformin lived longer then those who weren’t diabetic but didn’t take metiformin.

1 Like
#35

I’m not so much a “fan” of Sinclair but I greatly respect the fact that he’s an Aussie leading the field and based at a prestigious US Uni. But anyway…
FWIW I didn’t start taking metformin because this or that hero told me to. I started because I read stacks of papers that strongly suggested it protects against (some forms of) cancer. I’ve been taking it for about 12 years.

Part of my fitness regime is gym work and part is running. Over the last 3 years I have taken to running this thin, hazardous goat track that goes along cliffs near a beach. It is very hilly and difficult for me. I have always had to stop 2 times on the way out (net uphill) and once on the way back.
Just after Christmas I ran it and cruised through the steep incline on the return leg. I was in shock! Never did it before. I’ve done it each time since. I’ll be 66 in about 5 weeks.
I’m not saying metformin is helping my stamina, but it doesn’t seem to be hindering it, either.

7 Likes
#36

Yes, there have been a few bike hills I had to get off the bike and walk up when I was in my 30s. Now I can power up them in my late 40s. Not sure which supplement does this, but it’s either Rapa or NMN (my guess).

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#37

Are you really going to go eunuch though?

Living longer but getting Alzheimer’s or death from falls/fractures might not be that great. Low T also gets you poor concentration and depression - which could potentially decrease telomere length and “brain aging”. Mice don’t get Alzheimer’s. Estrogen may be great early midlife, but later on, it could be “bad” at least in older women - increased risk of stroke & CRP from estrogen = dementia. WHIMS trial showed estrogen therapy for older women ended up increasing the risk of dementia.

https://www.science.org/content/article/could-testosterone-ward-alzheimers

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#38

It seems Sinclair once again extrapolates nonhuman studies way too far. He’s a bit too sensational on claims without evidence. If you hear him right here, he literally claims a combination of GH, DHEA, and metformin might confer “immortality” (time 1:14) - it’s gotten to the point of hyperbole, not merely strong optimism.

If you have T2D sure - metformin is the first line to treat for T2D, but there’s no real evidence of metformin for “healthy” humans and there’s evidence against it.

His claim of reducing Alzheimer’s may be incorrect - there may be a higher risk of AD and at best perhaps neutral. Not to mention, I’m still iffy about his resveratrol claims that were a complete flop on the ITP. C57BL/6 mice on a high-fat diet + resveratrol weren’t likely to be translatable in the first place and the PI admitted resveratrol and Sinclair bypassed standard review through political pressure.

“Moreover, metformin exposure increased the risk of Alzheimer’s disease (HR: 2.13, 95% CI=1.20-3.79) and vascular dementia (HR: 2.30, 95% CI=1.25-4.22).”

“long-term users of 60 or more metformin prescriptions were at greater risk of developing AD (adjusted OR (AOR) = 1.71, 95% CI = 1.12-2.60)”

https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2012.03916.x

“Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]).”

The newest meta-analysis here says no benefit or protection (perhaps the negative studies are primarily related to proven increased vitamin B12 and other deficiency risks in metformin that have been corrected with increased awareness over time?):

“Results show that metformin has no significant effect on improving cognitive function or protecting against any dementia including vascular dementia and Alzheimer’s disease, and cognitive impairment as well.”

https://journals.sagepub.com/doi/10.1177/02698811211057304?url_ver=Z39.88-2003

We have seen metformin interfere with exercise in a good amount of humans in a trial. Why not go for exercise which is proven rather than something unproven and potentially negative or maybe at best neutral? We already know Rapa + acarbose > Rapa + met in mice if you’re going to be citing ITP trials.

As for “lower blood sugar must be better” - T1D hospitalized for just one blood sugar extreme = higher risk for dementia. I am aware of a few people who hit hypoglycemia several times and that may have increased their risk. Trying too hard to plug one hole leaves a bump in the road which could be as bad or even worse than the hole in the first place.

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#39

Honestly I have to shake my head at this type of anecdote.

I have measured power output for 99% of training sessions over the last 12 years. For me NMN had zero impact on any physiological metric (peak, anaerobic power, VO2 max and FTP) whilst Rapamune (at 8mg/wk) had a slightly negative effect. However the latter caused a significant weight loss that improved my W/kg. That is the loss in W were more than offset by the drop in kg.

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#40

Just another reason not to take it. Throw it in the bin along with your resveratrol and NMN.

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#41

The “weak mitochondrial poisioning” is most notable possible side effect to me. That resting lactate increases by a significant amount.

Very low blood sugar in general doesn’t seem like a good thing either, seems like the brain likes sugar.
Do you have an opinion of optimal resting glucose and max glucose spikes, as well as standard deviation?

1 — lower average blood glucose is better
2 —The more you can minimize glucose variability the better.

  • Say you have two people who both have an average glucose of 100 milligrams per deciliter (which corresponds to about an excellent HbA1c of 5.0 to 5.1)
    And one of them has a standard deviation of 10 milligrams per deciliter and the other one has a standard deviation of 20, the person with the lower one is better off.

From Peter Attia,

I like to see my patients with a mean glucose below 100 mg/dL, a glucose variability below 15 mg/dL, and, as noted above, no excursions of glucose above 140 mg/dL. After about a four-week intervention that included exercise changes and nutritional modifications his average glucose fell to 84 mg/dL, his glucose variability to 13 mg/dL, and he had zero events exceeding 140 mg/dL. If he can maintain this way of living in the long-run, it’s likely to translate into an improvement in healthspan and reduce his risk of glucose impairment.
Are continuous glucose monitors a waste of time for people without diabetes? - Peter Attia

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#42

That’s you. I am me. I am sure you are much more athletic than I am and probably things have little to no effect on you whereas they may have different effects on me. Yes, everything I relate is anecdotal and should be viewed as such. However, just because something hasn’t been measured empirically doesn’t mean its not real.

And something that may work for me may not work for you and vice versa. Of course empirical measured data should always be rated higher than anecdotes. But just like your weight loss, not everyone taking Rapamycin is going to shed pounds. We are all going to vary in our results.

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