Questions to Matt Kaeberlein

Some month ago the Optispan podcast was launched with the great Rapamycin researcher Matt Kaeberlein. The podcast has really high quality content so I can highly recommend checking it out. One of my really favorite episode series are the R-files which covers different topics related to Rapamycin. In the latest R-files people had the chance to send questions to Matt around Rapamycin which he then answered in the episode. So let’s gather some more Rapamycin questions for a future “Ask me anything” episode. Just comment below and Matt will be notified.

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Latest R-files podcast AMA

Effects on aged immune system

Bacterial infection

Rapamycin potential side effects and benefits

Offlabel experiences and doses

Introduction to Rapamycin

Interview with Jonathan An on Rapamycin periodental disease trial

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Maybe an episode on what diseases, if any, have clearly been shown to improve on Rapamycin.

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Thank you for all of these… Just watched one and learned some things.

Also, I was surprised his guesstimate is that fewer than 100k in the US are taking this.

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What is the dosing and regimen of rapamycin being used in Jon An’s human study of rapamycin effects on periodontal disease and how was that chosen?

In Dr. Sudha Seshadri, M.D Phase 2 Trial of Rapamycin for Alzheimer’s Disease the dosing of rapamycin will be1 mg per day. Does Dr. Kaeberlein have any theory why this dosing was chosen ?

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Another question for Matt (he’s on the advisory board for TriumVet):

What is unique about TriumVet’s rapamycin formulation?

Is it being sold yet?

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@KarlT Yes, that could be an interesting thing to get an overview of the field. Currently I think the main area is for organ transplant patient and some type of cancer treatment.

@Beth I think it’s quite few who take it for longevity purposes. I would quess more around 10k around the world. Or do someone else have any other estimate on this?

@Dr.Bart Yes, the dosing is something that would be nice to get an answer on. But I think they will land around 6mg/weekly. Also great question around the Alzheimer’s trial on the choice of daily dosing.

@RapAdmin Good questions, maybe he should interview Joshua Stern and make a deep dive in the results from the trial they did and what the next step is etc :+1:

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With dosing you also need to collate whether or not people use enhancers. (Grapefruit/Pomelo etc)

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How would he compare the evidence we have for SGLT2 inhibitors with mTOR inhibitors, considering the fact outside of results in ITP for both, we have large clinical trials showing benefit for kidneys and heart etc for the former. Which case is stronger for use in humans?

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I’m not interested in what it has been approved for, but rather what we, the beta testers have found. I.e. Matt might say it treats adhesive capsulitis.

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Well, I just love being in an elite club, and all ….

Seriously though… in his video above he said he thinks it’s well over 10k in the US but under 100k,. She said something to the effect of 40x that in the world (this is going on my bad memory)

I’m suprised so few considering the podcast reach of attia/ferris etc? I mean, that is where I learned about it!!!

Considering half the people taking it are in this forum!, do we have a page where we share our dosing schedule? I know I’ve seen many comments but wasn’t sure if there was an organized spot that had consolidated the info… similar to a voting post? I have been told the average is about 6mg a week (by my doc), but thought I’d ask.

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Also, after watching the video that once again mentioned canker sores, I want to be prepared because I’m a big baby. What does the hivemind say is the best treatment?

I am not taking daily lysine in the hopes it might help prevent this.

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Different people have different views on dosing. I am on the extreme on the delay between doses (whilst also taking a relatively high dose taking into account acceleration).

Its really hard to set up a system to monitor this as it is at least a 3 dimensional question (dose, timing, acceleration)

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I think you are right, I remember now Matt had Dr. An on the show and he discussed the dose titration for safety reasons and I think he settled on 6 mg/week.
So I guess, to contrast that, it would be great to learn from Matt about his theory why 1 mg per day was chosen for the Alzheimer’s study?
Does one need a steady trough level for blood brain barrier penetration or is there something about the Alzheimer’s diseases process that requires constitutional dosing?
BTW, Matt Kaeberlein is the one that wrote the editorial below, he is obviously very knowledgeable about the subject. Actually it would be great to have a whole episode about Alzheimer’s and rapamycin.

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Thanks. His thoughts on the timeline for lasting benefit of rapamycin after stopping. He takes long breaks. Does he feel the benefits of rapa are faster and last longer than the related detriments of aging? So he can claw back 2-20x of aging in x amount of time of rapa dosing ? What benefit of any would a person hope to get by continuously taking Rapa (say weekly dosing)?

Archetypes:

If you are heathy but have an issue with inflammation in a joint, take Rapa for a couple months (until issue resolves), then start again when the issue returns.

If you have chronic inflammaging, stay with Rapa for longer periods. Only taking short breaks to let the body recover every so often.

If you want to take rapa “forever” just because…use a longer dosing cycle to let the body recover all along the way?

This is what I’m thinking about now. Any input from Dr Kaeberlein would be useful

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Sort of - these rapamycin user polls are still open, so if you have not yet responded, you can:

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I’ve had occasional canker sores my whole life, and Triamcinolone Acetonide Dental Paste USP, 0.1% is very effective. It’s a prescription paste. You put a glob on the lesion right before bed and it’s like 90% gone the next morning. Discovering it was actually life-changing, because I would get canker sores so bad I couldn’t eat solid food for days. Not anymore!

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Peter Attia uses debacterol for Rapamycin-initiated mouth sores, and recommends it: https://www.goodrx.com/debacterol/what-is#

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@beth I use methylene blue for this and other purposes. When i do get a canker sore I dab a little MB on it…it goes away <24 hours unless it was from me bitting the inside of my cheek (I hate that), then it takes a few days.

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Rapamycin prompts the body to replace duff mitochondria. This is something to cycle. Once enough have been improved there are diminishing returns.

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@John_Hemming So, what the cycle? What’s long enough for enough newly damaged mitochondria to accumulate to be replaced upon Rapa prompting? I suppose we are talking about autophagy and mitophagy…what’s your guess on how long does mTOR need to be turned down with rapa (or energy deprivation) to create a signal for autophagy / mitophagy, and then how long to let the cells components / mitochondria be replaced and then give time for more cellular proteins/mitochondria get old/damaged to need another hit? I understand mitochondria half-life is only 8-30 days. Since you do a 3 week cycle, is that your answer?

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