Crowdsourcing a Study (PEARL 2?)

[anon99478646]

I see, so it sounds like you’ve adjusted your stance on whether metformin increases lifespan—you were certain before, but now you’re not as sure. However, you believe that rapamycin, SGLT2 inhibitors, LDN, and tadalafil might be more promising, and that combining them could lead to better results. I’m curious—what makes you think these particular drugs have greater potential for increasing lifespan or optimizing healthspan compared to metformin? Thank you.

[szalzala]

I think part of it is that the vocabulary has changed a little bit over the last 5 years. Specifically, this differentiation between healthspan and lifespan. Also, my answer from 5 years ago hasn’t really changed on Metformin - It probably has some lifespan benefits, but it’s probably limited and will surely be surpassed by other drugs. But just because it’s potentially limited value, doesn’t mean it has no value. I think that’s where I disagree with some of the changes in attitude to metformin.

For LDN, I’ve prescribed it to a lot of people over the last 10 to 15 years and some of the reports from patients makes me fairly confident that there’s something about LDN that’s impacting the aging process. We sponsored a mouse longevity trial through the University of Washington which should be completed as soon as the final mouse actually passes away - But indications seem very promising that LDN extends lifespan in mice when started in middle-aged (and I would be willing to bet that it would have even bigger impact if started earlier in life)

SGLT 2 inhibitors and PDE5 inhibitors have both recently had studies come out showing the potential for longevity with impressive hazard ratios for both diseases of aging, as well as general mortality. Of course, these sorts of studies are only correlative and we cannot draw any causative conclusions. However, to me they’re impressive enough to pay attention to. And given the safety profile of both of these medications, make them ideal candidates.

Rapamycin and canagliflozin are among only a small number of molecules that have shown longevity benefit in the ITP. I wouldn’t be surprised if tadalafil is taken up by the ITP soon. Unfortunately, LDN was not taken up by the ITP and it seems that more practical dosing aspects need to be worked out before they will take it up (The University of Washington study is using daily injections, which is impractical at the ITP)

[Neo]

@szalzala

and SGLT2 inhibitors are more promising

Hi @szalzala - thanks for the posts above

Several of us participated in the small Cana pilot study you ran in the spring

• will you be sharing any of of those results in any form soon?
• any update on whether you will start offering any Cana or SGLT2i product?

[szalzala]

Thank you all for those who participated.

Our statistician and medical writer has been busy with the PEARL and bioavailability papers.

The canagliflozin paper should be up next.

And then we have several other papers that we want to publish on a variety of different topics, including metformin quality of life opinions on defining health span, LDN opinion paper as a longevity drug, and a couple more

[anon99478646]

Thank you for your great response and the insightful information on these longevity drugs. I’m sorry to hear about Alan Green and Dr. Blagosklonny’s passing recently. Were there any final studies or projects you were collaborating on that might still be published? It would be fascinating to see the results of any ongoing work you had together.

I also wanted to mention that I’m really impressed with the members of your board. I noticed that the founder of the Institute of Integrative Nutrition is now on the board—congratulations! Are there any upcoming articles in respected newspapers or journals, like the NYT piece, that we can look forward to?

[szalzala]

We had conversations with Dr Blagaskloni and Dr Green early on in our company’s history where they help provide some advice on the PEARL trial. After that, it seemed like they were less available. I would love to find a way to be able to analyze Dr Green’s patient database information because he has one of the largest databases on rapamycin users. But I have no idea how to go about obtaining those records.

As for our advisors, Joshua Rosenthal of IIN fame was one of our earliest investors. We’ve been fortunate with some of the investors and the advisors that we’ve been able to work with over the years.

We’ve had a few conversations with other media outlets and a few more scheduled. It’s always hard to say what kind of story, if any, they’re going to run.

[John_Hemming]

I think what is needed is for more people to do my sort of biohacking experiment recently. The testing costs about GBP300 per week. This is far more than the rapamycin direct cost. Hence the overall cost is about GBP2K, but it provides useful information.

[José]

@John_Hemming

…“The testing costs about GBP300 per week. This is far more than the rapamycin direct cost.”…

GBP1200 per month / $1,561.03 USD
per month at todays exchange rate 10/16/2024

How many members on this forum has $1500.000 per month in disposable income for testing?

[John_Hemming]

That is, of course, a constraint. However, some do.

[DrFraser]

I put about $300 into labs quarterly, and am pretty happy with that approach. I probably put $1000 into meds and supplements quarterly. I don’t think I’d like to put more resources in, as I also don’t know what actions I’d have based upon results. So I’m happy putting in 1/3rd for @John_Hemming does. He must have deeper pockets than I do - and I make a pretty good income.

[John_Hemming]

Because what I am doing is often at the leading edge of knowledge I am concerned to identify any problems more rapidly. A CGM costs quite a bit, but you don’t need to use it all the time. A weekly full panel test in the UK is about GBP150. However, I do other testing as well and my normal annual costs are quite high.

On the other hand in 2019 I sold a business I formed in 1983 so I am reasonably well off. As I am in my 60s I have no mortgage now.

Realistically the experiment I did with an effective dose of around 77mg of Rapamycin is not something I have seen elsewhere. People have taken higher doses, but I have not seen any testing results. Particualrly the glucose testing is interesting. We know Rapamycin affects glucose, but not exactly how.

It will be different for different people. However, we do now have a published datapoint. There will be more data next week when I get the final blood panel results.

[José]

Reality is an individual own outcome, everyone is different and a “fit one for all solution” does not work.

As posted in June 2022;

The n-of-1 Clinical Trial: For Longevity Drugs?

The ultimate goal of an n-of-1 trial is to determine the optimal or best intervention for an individual patient using objective data-driven criteria. Such trials can leverage study design and statistical techniques associated with standard population-based clinical trials, including randomization, washout and crossover periods, as well as placebo controls. Despite their obvious appeal and wide use in educational settings, n-of-1 trials have been used sparingly in medical and general clinical settings. We briefly review the history, motivation and design of n-of-1 trials and emphasize the great utility of modern wireless medical monitoring devices in their execution. We ultimately argue that n-of-1 trials demand serious attention among the health research and clinical care communities given the contemporary focus on individualized medicine.

At the end of the day, the only thing that is of value is does it work for you.

[John_Hemming]

The argument against n of 1 is that there is a placebo effect. My argument is that although the placebo effect is at times reasonably good it is not enough to move the dial very far on long term health.