#10

Nir Barzilai must like this.

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#11

But did Nir Barzilai actually have anything to do with this study, or are the authors quoting him to give the article merit? It looks like the latter to me, and that makes me more suspicious of the findings.

(However, I do take Metformin with my Rapamycin so I am hoping the article is true. Yet, I am skeptical.)

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#12

Ask him.

Contact information;

Metformin is inexpensive insurance, with a possible HIGH benefit payment.

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#13

See the framework that @adssx laid out about this

Just saying china and then judging is not the optimal way to engage with data

At a high level perhaps at least ask

  • what country AND:
  • what institution/city (This paper would rank higher on that metric)
  • what journal (this is arguably one of the worlds top 2 scientific journals…)

And then, given that (2) and (3) look good, it’s probably worth looking at the paper and its data and methods + see what other top scientists seems to think about it

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#14

I am already following the paper’s recommendations, so, as I stated earlier, I hope it is correct.

I’m afraid I have to disagree with #2. I live in China, and although the institution that wrote this paper is in Beijing, it still doesn’t instill confidence in me. It’s a Chinese mentality issue and this issue has been getting much worse recently as the government slides further into dictatorship. When people are scared for their jobs or freedom (or life) they’ll produce results needed to keep their job or freedom.

This gives a good idea of the current environment in China.

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Here in Hong Kong, a new precedent has been set this year. A protestor was convicted for 10 years. The lawyer defending him also received the same sentence for defending someone who was obviously criminal. That is the China of 2024.

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#15

Using the FDA conversion guide, the human equivalent dose of 20 mg/kg in cynomolgus monkeys is 6.4 mg/kg (20 x 0.32). So, about 500 mg/day for most adults (but only 384 mg for a 60 kg human, for instance). My concern about metformin has always been medium and high doses (>= 1 g/day), and I wondered whether low-dose could be beneficial. This article strengthens the case for low-dose metformin. (It would be good to have something like 250 mg ER on the market.)

However, Eric Topol wrote the opposite: did he make a mistake?

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Given that the dose is low, could it just be that many of these monkeys (if not the majority) had diabetes, prediabetes, or just suboptimal glycemic control, and metformin fixed that?

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What's the Deal with Renewed Interest in Metformin?
Parkinson's disease
#16

FWIW…

The proposed TAME study dose is 1,500mg per day.

Those who are not aware of the proposed TAME study review:

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#17

An older Barzilai{in my view “The Metformin Master”] paper.

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#18

You are creating a straw man and not addressing what I am saying

Help me understand what you don’t agree with

  1. There is a lot of crappy research and even fraud and false data being published

  2. This happens everywhere, but even more for instance China than most western countries

  3. We should in general be skeptical of results of a single paper that are not reproduced or at least well triangulated with other known data and publications

  4. Item (2) means that one should on average be more suspicious about a Chinese paper vs a US paper

  5. But while China might be producing among the most false papers in the world, they also have been making massive investments in the science sector of their civilization and an increasing % of the world’s scientific insights and scientific successes are coming from China - partially just do the shear size of their scientific community and the amount of investment going into the sector

  6. So the goal should not be to throw the baby out with the bath water, but to try and capture the stuff that actually is good

  7. Some ways to look at that is to look at where the paper was published, what the track record of the authors and the the institution has been in the past

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#19

I agree with 1-4. I disagree with 5 on. When 50% of a country’s papers are garbage, I’ll need supporting evidence from another trusted source before I even consider it.

Remember that Dr. Sinclair is from Harvard, the most trusted university in the world. Yet, I don’t trust the Resveratrol research.

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#20

@DeStrider

I’m not saying that you should trust

I’m saying when something warrants attention and triangulation. (And the good thing with metformin is that we can triangulate it a lot).

Anyway, no need to discuss this further on my end

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#21

Many human aging clocks have proved unreliable. So, I’m skeptical of a new aging clock for monkeys. Additionally, their metformin treatment group included only 6 monkeys.

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#22

You sure about that?

The Nature article about the paper says:

This led Guanghui Liu, a biologist who studies ageing at the Chinese Academy of Sciences in Beijing, and his colleagues to test the drug on 12 elderly male cynomolgus macaques (Macaca fasciucularis ); another 16 elderly monkeys and 18 young or middle-aged animals served as a control group.

#23

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https://diabetesjournals.org/care/article-abstract/doi/10.2337/DCa24-0032/157171/Prevalent-Metformin-Use-in-Adults-With-Diabetes?redirectedFrom=fulltext

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00299-2/fulltext

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#24

Are there papers on other glucose-lowering drugs such as SGLT2, DPP4 or GLP-1RAs? Said otherwise: is the positive effect of metformin seen here only related to its glucose-lowering properties or is there something else?

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#25

Scattered through out the paper “Metformin decelerates aging clock in male monkeys” is “O-Met, n = 6”. The paper defines, “At the start of the study, monkeys were evenly divided by age and randomly assigned to either the metformin or vehicle treatment groups (hereafter referred to as O-Met and O-Ctrl).” So, yes, I’m sure the paper only treated 6 monkeys.

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#26

China is the world’s largest patent applicant, the world’s largest international patent applicant, the largest international journal publisher and citation country, and has surpassed the United States for ten consecutive years!

#27

But, according to investigations, 50% of it is fraudulent. That’s compared to 10% in most other Western countries.

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#28

Thanks. So weird that the Nature story about the Cell paper for it so wrong! How on earth could such a good journal write the following when the N is actually 6:

This led Guanghui Liu, a biologist who studies ageing at the Chinese Academy of Sciences in Beijing, and his colleagues to test the drug on 12 elderly male cynomolgus macaques (Macaca fasciucularis ); another 16 elderly monkeys and 18 young or middle-aged animals served as a control group

Do you mind sharing the Cell paper btw, I was not able to access it and would love to read the real thing.

#29

During the pandemic I believe nir barzilai discussed why he thought it would/was working - that might be one place to start (think is was more about other inflammatory and immune related pathways or something but was a few years ago so I’m not sure).

Haven’t read the more recent papers on Met and Covid but they may have different biomarker data and may also discuss their mechanistic understanding/conjectures.

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