Metformin - Based on latest 2022 info, Any health / lifespan benefit for Non-Diabetics?

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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If you don’t collect the data you’re just pi$$ing in the wind. It’s simply bad science.

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I understand we should trust the science, but the best we have right now are the ITP results. There probably isn’t going to be a human trial any time soon as Rapamycin is off patent. As more data flows in, we’ll be able to make better decisions. For now, our experiences as Rapamycin users are hopefully a benefit to the members of this community. If you disagree, that’s your prerogative.

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Your opinions are equally as valuable as mine.

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No, if I provide DATA that is manifestly superior.

My epigenetic lab data after taking Rapamycin was 7 years younger. What’s yours?

Honestly, if I upset you that badly, just use the ignore feature.

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[quote=“DeStrider, post:48, topic:4798, full:true”] I know its hard for someone with your mental capacity to figure that out. But heres hoping.
[/quote]

Ahaha

Some time in the future you’re going to reflect and realise, ‘that guy was right… I introduced a multitude of drugs/supplements simultaneously and didn’t collect any data.’

Your last comment made me smile because deep down,I think you may be right. I embrace things too optimistically and I really need someone to temper my enthusiasm. For that, I thank you.

But you sure know how to push my buttons.

And I wonder if you’ll ever read this since you probably found the ignore button.

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What data do you collect?
Also, to really “test” a drug or a supplement, it is possible to do ‘self-blinding’ studies which are gold standard, and do statistical analysis.

Here is an example of adderall self-blinding:

Vitamin D:

Modafinil:

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Quarterly blood tests plus Oura ring for sleep quality, resting HR, HRV and body temperature etc. I have also recorded body weight and training data every day since 2011.

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Again and again, this is why people should actually read the references and not get caught up in “medicine 3.0” hype over listening to “sciency” blogs. I’ll pick it apart this time, but the broader theme here is it’s easy to hold illusory confidence for anyone (including physicians btw) that they “know something” and makes them feel they are special because they know something beyond what the scientific/medical community knows.

CGMs aren’t proven to be useful in nondiabetics - there is negligible evidence. I am quite familiar with the literature Attia has cited and have deeply considered it. None of the cutoffs Attia uses is supported by any evidence he cited - it appears to be arbitrary.

If you read his assertions in the article and pick apart the references - which almost nobody does - what he is claiming is clearly without evidence. The 2018 study he cites suggests that glycemic dysregulation is not fully captured by traditional metrics - but it does NOT suggest that the classification of excursions above 140 mg/dL provides more than traditional metrics - it might or it might not. Some people have highly variable individual glucose levels.

The study he cites does not confirm any evidence of glycemic variability readings with outcomes. Even if it did, there is no justification for using CGMs in patients broadly for more than 2 weeks as a short diagnostic. Glycemic variability may be only indicative of poor health rather than causal.

If you read his citation: Postprandial Hyperglycemia and Glycemic Variability | Diabetes Care | American Diabetes Association

“The biggest gap still is the missing evidence as derived from randomized prospective intervention studies targeting postprandial hyperglycemia and seeking to reduce hard CV end points. In fact, there has been some stark disappointment recently in this context. As this evidence by intervention is, however, key for the ultimate approval of a treatment concept that it is mandatory to care for postprandial hyperglycemia and glucose variability beyond achieving appropriate glycemic control as assessed by HbA1c, the current net balance of attained evidence is not favorable that we should care.

If you read further in your cited blog post:
" Prospective studies show that higher glucose variability in nondiabetics is associated with an increased risk of cardiovascular disease, frailty, cardiovascular death, cancer death, and death from any cause compared to lower glucose variability."

Look at the actual citation for AD and it only says hyperinsulinemia.

Look at the citation for frality and it only says HOMA-IR.

And so on…

Nowhere does it say glucose variability or mention any cutoff of 140 mg/dL. None of them use CGMs. They use either OGTT or HOMA-IR.

There are a lot more flaws in the article. I’m not going to pick through all of them.

That being said, I do use a CGM for data gathering purposes (there is no proven use for this - the data might end up being mostly useless), but it is NOT for prevention because it’s NOT a cost-effective approach and there is no real evidence for wide use. I would not recommend one for non-diabetics if they are seeking preventatives until there is real evidence.

It is quite possible CGMs could provide biofeedback that could increase adherence to lifestyle interventions for nondiabetics, but that is not demonstrated in a randomized clinical trial. It’s far easier to go beyond the evidence to recruit patients to pay 6 figures a year - CGM is a big part of that - especially if you understand his background and track record of going far beyond the evidence on NuSI which he quietly withdrew from when it burned into the ground so far that he had to jump ship as soon as there was smoke.

He has been a huge proponent of LC diets, despite the lack of evidence, and despite the NuSI debactacle. So it’s not particularly surprising he is going after glucose variability, but he neglects mentioning common confounders - postprandial triglycerides as an independent risk factor for early atherosclerosis, which also affects downstream dementia risks. Even if he is right about glucose variability - it is quite plausible trading carbs for fat is just trading one issue for another. He does not even mention that once. He is making assertions without evidence, including completely arbitrary ones.

Let’s illustrate it in a simple hypothetical example: if one has a twin brother with almost identical metrics and lifestyle - then one trades eating blueberries for say sausage because sugar levels go slightly over 140 mg/dL - are you sure that glycemic variability matters (assuming it turns out to be later supported to some degree)? Eating more sausage (or processed meats in general) has suggestive evidence for early atherosclerosis and dementia, as well as cancer. Unprocessed red meats may also be the case, perhaps beyond a certain rough threshold of intake, but we are not certain. So would one still keep eating sausages instead of blueberries based on glycemic variability with evidence showing (1) the other twin is not getting diabetes/glucose intolerance with blueberries (2) the first twin brother is having early atherosclerosis with carotid ultrasound/CAC? Probably not. There are plenty of other variables not captured.

So again, I suggest you avoid “influencer” blogs and social media to sway against facts - it’s easy to get caught up - I originally thought maybe Sinclair’s resveratrol claims could have merit until I actually read through the citations and other papers very, very carefully - then I realized he is going way overboard as a business strategy with high certainty. Historically, proposed longevity interventions are fraught with hyperbole for so many decades, so we should be particularly wary of the need to be vigilant and meticulous. Attia has a few guests I admire such as Dr. Matt K and Dr. Miller who recognize hyperbole is detrimental to their reputation in their scientific career for their peers and the “aging” field that is already fraught with hyperbole in general. Again, Attia is not a reliable source and he has a track record of doing that with incentives to do so - leaping beyond the evidence significantly - although I suppose he learned a bit from his first excursion with NuSI to temper that to a lower amount. Attia’s voice is amplified by other mini “influencers” on social media, despite clearly a severe lack of evidence and you end up with groupthink. I hope you can see the real issues here and I suggest you actually dive deeper than blogs/podcasts/the like.

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Thank you. So I think objectively speaking, CGM’s wouldn’t be a top priority as an intervention tool based on the evidence we currently have. It’s basically grasping at straws and unnecessary optimization. It looks to currently not be a significant factor in the determination of different outcomes compared to the current tools we have (HbA1c?). The CGM industry would love that 300 million Americans would start using CGM year round. It’s more significantly more expensive than rapamune, statins, etc.

I think many of us understand the limitations of the intervention, based on the other evidence we have, so if I have money to “waste” for small positive gains. Would you say that lower glucose peaks and average glucose is better? I would think for example it could entail adding more fibrous foods to meals, maybe some more PUFA or MUFA instead of carbs but not too much of a change. Or do you think differently?

Also to be clear, I put a very low expected value to be gained from this intervention, right from the start. I wasn’t clear about my uncertainty, but it is high for CGM. Much higher than for other things, and a smaller expected benefit.

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FWIW

I See…“Carnac the Magnificent”

What will occur/is occuring will be a “smart watch”. For a fraction of the cost with many{Temp, BP, HR, ECG, blood glucose, BO², sleep and more] data collection sensors for low cost, less than $75.00.

Devices are already available.

Near future will be connected to program’s with AI, people will have their own “Personal Medical Expert”. The Medical Industry will be totally changed.

Carnac the Magnificent

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I suggest you read up how “AI” actually works - most likely before that happens, almost every other job will be automated. One may want to stay alive for 40+ years at least if you even believe a singularity is plausible. Very few parts of sci-fi actually panned out so far. Not only that, Alphabet recently gutted a big part of their consumer health devices in favor for working with docs directly partly due to futility and macroecon conditions.

Here are estimated probabilities of each job in the Appendix of some research into job automation by some Oxford professors, I suggest you take a look and how they estimated it.

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The real fact is…

One of us will be correct the other will be wrong.

Only the future will decide.

And it will be in our lifetime.

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What’s your HRV? Mine is around 35 - 40 and I cannot seem to get it any higher. Any suggestions?

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Yes, mine is not much higher unfortunately. Cold showers seem to give it a ~5 point boost but they’re not something I especially enjoy! It’s also consistently highest in July and August so perhaps natural light has an influence.

I know from my wife’s data that alcohol has a negative effect and if I take a break from training it starts falling after a few days. I take Mirtazapine and there’s research to show that is another negative influencer…

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I just saw this news on Metformin, and now I wonder whether I should continue taking it: “Furthermore, current CRMs such as metformin, when administered at day 10 of C. elegans’ adulthood or 20 months in mice, instead shortened lifespan and accelerated age-related pathologies (Espada et al., 2020; Zhu et al., 2021). Interestingly, we found that in C. elegans , rilmenidine prolonged the lifespan to the same extent (approximately 33%) whether exposure to the drug was initiated during youth, day 1 of adulthood, or when old, day 12 of adulthood (Figure 1c,d, Table S1).”

source:

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13774

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We are not worms. We are not mice.
The value of metformin in life extension is unquestioned in my opinion.
The better question for you is; at what age should you stop taking it as its value to the elderly is in question.
As has been posted before, metformin seems to have benefits beyond its ability to control blood sugar.

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Sort of a shame with metformin. I used to prescribe it widely but I don’t see much usefulness anymore. Certainly the evidence for life extension is pretty weak at this point.
On the other hand, we’re getting enormous results from the GLP 1’s like semaglutide and tirzepatide. It’s virtually a cure for metabolic syndrome as it reduces weight, glucose, lipids, and even blood pressure. The side effects are very minimal if titration is slow and careful.

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