Thanks! This was a great Matt Kaeberlein interview – confirming what we know about rapamycin - a few possible maybes, but as always Matt is not one to over speculate - is comfortable saying no research on things yet - or we just don’t know.
Which is why he remains one of the few researchers on rapamycin that I (and others) trust and respect.
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I agree, @Agetron. We are all acting on our own hypotheses that go well beyond what the available evidence can reliably inform. It is nice to hear him confirm that.
Thank you, @Krister_Kauppi for trying to get all of us satisfaction on our questions!
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@Krister_Kauppi Nice work! I’m impressed with how you have made a mark in the longevity space through intelligent effort and persistence. Well done! And thanks.
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@Krister_Kauppi Yes. Thank you Krister for compiling the questions!
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Notes from video —- several surprises
- don’t worry about diet or cardio exercise around Rapa dosing
- no rationale for limiting protein around Rapa dosing
- muscle gain might be better without Rapa. Take Rapa holiday to gain muscle, then hold onto muscle while dosing Rapa. And better to avoid resistance exercise the day before and day after Rapa dosing
- no data exists on mTOR rebound. Fasting followed by overeating may have negative consequences
- doubling dose (12mg vs 6mg) while doubling dosing cycle (2 weeks vs 1 week) will result in higher peak of rapa and longer period of time with no detectable levels of rapa vs weekly. Is one better? Higher peak probably better delivery to organs that are hard to reach (brain?). A guess.
- Matt started doubling his dose/period (16mg every 2 weeks)
- does tolerance to rapa develop? No data. But a guess is it’s possible but daily dosing in mice still works.
- what is a good trough rapa level? Undetectable for at least a few days a week before next dose. Low blood rapa doesn’t insure no mTOR inhibition in organs
- no evidence of bone loss in humans from rapa. Rapa promotes regrowth of oral bone. A ton of rapa might hurt bone.
- becoming convinced that 1x/wk Rapa preserves muscle
- sglt2 inhibitors vs mTOR inhibitors? Sglt2 benefits probably best for people with metabolic issues while rapa seems to address aging in general (my interpretation? Maybe better side effects for rapa but no proof
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Actually, Matt got this wrong. There is data on humans regarding mTOR rebound. Based on the study provided by McAlister, at 20 mg or less, there is no rebound. At 40 mg, there’s a 50/50 chance. Most people don’t dose over 20 mg, so it’s not an issue for most, but somewhere between 20-40 mg, rebound in humans becomes an issue. So, I’m staying at 21 mg. I’m living on the wild side. 
I’m more worried about mTOR2 inhibition. @Krister_Kauppi maybe you can ask MK about this? How big of an issue is this and at what levels do we need to worry about it?
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@Krister_Kauppi thanks for your efforts on getting the questions to Matt. You’re really helping move things forward.
You may want to include (and we may want include when we post a question) a link to the research that we are asking about - so Matt and his Optispan people can review the research beforehand. For example, the full thread on MTOR rebound would ideally be something that I think Matt would be interested in reviewing prior to answering: Rapamycin / MTOR Rebound effect in 3/12 non-GF and non-Keto patients
In many cases we’ve discussed and dissected these types of issue more than Matt likely has - so it would be good to bring him up to speed on the research and discussion.
Did anyone else notice the Easter Island Moai sculpture in the background of the podcast 
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Nice summary. I heard a few points slightly differently than you did.
He said there might be a case for avoiding resistance training the day of the dose and the day after. He did not mention the day before the dose. (He also mentioned this was speculative since it is not currently known if there is an impact.)
He said he has been taking 8mg per week since January.
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One other point I found very interesting was the comment on how quickly your blood sirolimus levels might be going down to under 1ng/ml. It was interesting that Matt tested at day 3, 4, 5… and found that it was already below 1 ng/ml after day 3. I had not considered testing earlier than day 6 or 7, but now I will test earlier. This might be a reasonable indicator that you’re “safe” to try higher doses if you’re not getting significant side effects, and you’re dropping to under 1 ng/ml after a few days and you’re at that level for a few days prior to your next dose.
So - I’ll use that new service from Healthspan $25 Rapamycin blood tests
and test at day 3, 4, 5, etc. when I’m on a weekly dosing schedule, and perhaps try testing at days 7, 8, 9, 10… if dosing on a once every two week schedule.
If other people try this, please post your results.
I also am interested in doing this with Everolimus. I will also try the blood sirolimus level test after dosing Everolimus, as I wonder how specific the test is and if it can differentiate between sirolimus and everolimus.
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Just did here Blood concentration of rapamycin (N of 1 dosage, model and biomarkers)
BTW the optimal protocol to fit the rapamycin pharmacokinetics is 2h for peak then 24, 48 and 96h
As you can see in my results that’s enough to get a very good fit.
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Do you have a spreadsheet you can share for others to create similar graphs from their experiences and tests?
How did you create the graphs? (what app)?
I wrote some Julia code for that. Too complex for a spreadsheet.
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How hard is it to use the code you wrote?
If we install Julia per: Download Julia
would it be pretty simple for non-SW engineers to operate?
Perhaps you could share the code on GitHub?
@Barnabas
I think you are correct about the first point. It was day of (not day before) and day after Rapa dose.
The second point you must have missed. Later in the recording Matt said on his last dose he doubled to 16mg and a 2 week cycle.
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@DeStrider: Great point! Add this as two questions as comments to the specific youtube episode because Optispan reads the comments and I think they have good potential to be added to a future AMA.
For all other people in this thread. Just add further more questions as comments to the youtube episode and the Optispan team will try to include them in future episodes. Remember as @RapAdmin said to add study to the question or discussion thread from here if such exist. That way we hopefully get a much deeper answer to our questions.
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AnUser
#166
That makes sense to me, with 5% absolute risk for genital infections with SGLT2i within study period.
Good catch. I wonder what any of us could look for if we tried a 2x dose every 2 weeks to see if it’s “better.”
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I will clean up the code and push that to GitHub.
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It is what I have been doing. The benefits are less side effects for me. I am able to build muscle quite well on this schedule as I am off Rapa for much of every month (I also take off every 5th week). As far as longevity benefits, I couldn’t say.
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The Scientific American article is a good read. Who knew (I didn’t)
Most of the vitamin D in modern supplements comes from irradiated lanolin, a grease derived from sheep’s wool. Steenbock also found that feeding dairy cows irradiated feed or mixing irradiated fat extract into milk raised D levels. Today fortified milk and other dairy products—which also use the lanolin-derived form of the vitamin—are some of the most common dietary sources.
and
In 1936 the Joseph Schlitz Brewing Company introduced “Sunshine Vitamin D” beer. The ads exclaimed that “beer is good for you—but SCHLITZ, with SUNSHINE Vitamin D, is extra good for you. Drink it daily—for health with enjoyment.” If it sounds antiquated, consider that in 2022 beer brand Corona launched Corona Sunbrew, a nonalcoholic beer fortified with vitamin D.
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