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What is metformin's secret sauce?

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Re: What is metformin's secret sauce?

#51

Post by chasil »

dinfinity wrote: post #35
jonplackett wrote: post #19

I don’t get it. Why would decreasing the function of mitochondria be a good thing? Can anyone explain?

I also did not understand why it would lower blood glucose, but that is due to my lack of understanding cells. I asked some help from ChatGPT and got this info: "Inhibiting a mitochondrial complex (e.g. one of the electron transport chain complexes) would decrease a cell’s ability to generate ATP through oxidative phosphorylation. As a result, cells would rely more heavily on glycolysis to meet their energy needs, wh…

This is interesting in that cancer cells rely more strongly on glycolysis.

I wonder if this effect results in more waste products, and if autophagy can reverse it.

Re: What is metformin's secret sauce?

#52

Post by garganzol »

flocciput wrote: post #50

For one of my friends, metformin was the key for finally losing weight. It got their insulin resistance under control, which had been causing them to crave food constantly throughout the day, way more than someone with normal insulin sensitivity. They never realized most people are not constantly hungry and thought people who were thinner just had way better impulse control or something, and that giving into that cra…

When someone "eats less", insulin sensitivity also improves, in theory. But the catch is that situation represents a vicious cycle: if you just eat less, you also get less nutrients, and it may be not sustainable if you eat highly-processed foods lacking the nutrients in the first place.

So a better idea is to eat less + consume more vitamins + consume more natural foods (to get those vitamins). Junk food + metformin combo works to some degree but in the long run it is more like a hack than a proper fix IMHO.

Re: What is metformin's secret sauce?

#54

Post by virtue3 »

garganzol wrote: post #52
flocciput wrote: post #50

For one of my friends, metformin was the key for finally losing weight. It got their insulin resistance under control, which had been causing them to crave food constantly throughout the day, way more than someone with normal insulin sensitivity. They never realized most people are not constantly hungry and thought people who were thinner just had way better impulse control or something, and that giving into that cra…

When someone "eats less", insulin sensitivity also improves, in theory. But the catch is that situation represents a vicious cycle: if you just eat less, you also get less nutrients, and it may be not sustainable if you eat highly-processed foods lacking the nutrients in the first place. So a better idea is to eat less + consume more vitamins + consume more natural foods (to get those vitamins). Junk food + metformin…

Your body is also not designed to lose weight. And will quickly adapt to the reduced calorie count and halt weight loss.

I’ve done a lot of self work in this area and honestly glp-1 drugs and metformin provide a pretty serious ability to make weight loss manageable.

Intermittent fasting is also an effective way to deal with insulin sensitivity but it does involve a large lifestyle switch.

Re: What is metformin's secret sauce?

#55

Post by esperent »

garganzol wrote: post #52
flocciput wrote: post #50

For one of my friends, metformin was the key for finally losing weight. It got their insulin resistance under control, which had been causing them to crave food constantly throughout the day, way more than someone with normal insulin sensitivity. They never realized most people are not constantly hungry and thought people who were thinner just had way better impulse control or something, and that giving into that cra…

When someone "eats less", insulin sensitivity also improves, in theory. But the catch is that situation represents a vicious cycle: if you just eat less, you also get less nutrients, and it may be not sustainable if you eat highly-processed foods lacking the nutrients in the first place. So a better idea is to eat less + consume more vitamins + consume more natural foods (to get those vitamins). Junk food + metformin…

Learning to eat healthily is a skill. It's a separate skill to learning to eat less.

I don't think any amount of junk food would get you adequate nutrition. So reducing the amount of junk food is a great first step.

You can take a multivitamin, it'll be enough to survive. Later, once you've established a decent calory baseline, you can start to optimize your good for nutrition.

Re: What is metformin's secret sauce?

#56

Post by amanaplanacanal »

robocat wrote: post #34
lordnacho wrote: post #6

Earlier quoted context omitted.

How do people come to find these drugs then? If you don't have a theory about how something works, what would make you test whether it works?

A fabulous book on this is Phenethylamines I Have Known and Loved (PiHKAL) which can be found as a PDF online (the link I had has died but try Google and filetype:pdf). Summary: a chemist is interested in psychedelics so he starts creating candidate psychoactive substances, and he then tests them on himself and friends. He wrote a lovely book about his journey.

Also its mate Tryptamines I Have Known And Loved.

Re: What is metformin's secret sauce?

#57

Post by JALTU »

vlod wrote: post #2

FTA: "But until now, scientists have been unable to determine how, exactly, the drug works." Try that next time you submit a PR: Yeah... it works, but "I am unable to determine how exactly". I find this concept absolutely mind blowing. We take drugs that the creators of the drugs don't understand how they work. I realize that biology is hard to understand, but this sounds crazy.

Yes! I am a "glaucoma suspect" meaning that short of going blind, I have the eye and eyesight degeneration characteristics that suggest I have the disease - no known causal factors. So I am treated with an expensive eye drop drug, rhopressa. In the fine print of the paper that comes with the drops is, and I paraphrase, a disclaimer stating the drug's active mechanism is "unknown."

But my ocular pressure is definitely 30% lower than when not using rhopressa! (shrug)

Re: What is metformin's secret sauce?

#59

Post by elcritch »

falcor84 wrote: post #40
groby_b wrote: post #33

Earlier quoted context omitted.

> How did folk medicine come to know the effects of guanidine? Dunno. The same way we know a lot about other things in the chemistry domain - somebody tasted it, just to see what happens. "Mendeleyev's Dream" is a great book that contains many fascinating anecdotes of people going "let me just lick this, just to try". (Or, if you want to go more modern, the history of hallucinogens is pretty fun too) Humans seem to h…

Indeed. I would assume that this is one of the traits that survives due to group selection [0] - it would be bad if everyone in the population was such a risk taker, but groups that have a small percentage of these people will adapt better. [0] https://en.wikipedia.org/wiki/Group_selection

That's my belief on why ADHD has such similar levels of prevalence (between 5%) around the globe despite drastically different cultures and varying genetics. It's great for the group as a whole as the ADHD members tend to be natural entrepreneurs, inventors, etc. However it often sucks for the individual ADHD folks and leads to higher rates of, well, everything. So the equilibrium settles to a stable fraction of the overall population.

Re: What is metformin's secret sauce?

#60

Post by tssva »

2lazy2pwdmgr wrote: post #58

One downside is they are huge pills (500 mg), and a beneficial effect typically requires taking more than 1 g/day.

I take a 1000mg metformin tablet twice a day. I wouldn’t call it huge. It isn’t significantly larger than my daily Allegra and is much smaller than the vitamin capsules I take daily.
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