#13

If I used acne as a limiting side effect, my max dose would be zero.

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#14

Those are my thoughts exactly. The day after taking rapamycin, I increase my protein intake and exercise, both activating mTORC1 signaling.
Because I was late to the game, my personal premise is high peak and moderate AUC. I am hoping that the high peak causes some crossing of the BBB.
I am a believer in Dr. B’s dosing regimen. I.e., older mammals starting rapamycin need a higher dose regime.

When I first started at high doses my lipids and glucose levels rose. As I was over my “ideal” weight by 10 - 15 lbs., losing the extra weight took care of most of the problem. Depending on your viewpoint my lipids are excellent and my fasting glucose levels are always below 100.
At this time I am taking ER Dapagliflozin (10mg) + Metformin (500mg), Bempedoic acid,180mg, Ezetimibe (10mg), and acarbose once daily.

I usually feel tired the day after taking a dose of 5 mg metformin+ GFJ. Other than that, I feel great.

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#15

The Kaerberlein McCormack conversation had so much potential but they got into many conversational “nested loops” and failed to fully conclude the discussion on all of the most interesting points.

McCormack touched on the holistic benefits of breaking down and rebuilding our bodies systems. Conventional wisdom suggests that 330 billion cells are replaced daily, this is the equivalent to about 1% of all our cells. In less than 100 days 30 trillion cells will be replenished which makes a new you. For me, the magic of Rapamycin is in stimulating our bodies into autophagy and therefore breaking down and destroying our old, damaged and and abnormal proteins and other substances, and recycling these substances for other important cell functions, or to be discharged from our bodies. As McCormack implies, if we don’t purge our bodies of this detritus our body suffers.

There are so many issues that could vary Rapa doses: body composition, weight, health, diet, the interactions of drugs and supplements, exercise, genetics, age and how we enhance the dose ie GFJ.

@DeStrider My feeling is that my Rapamycin 6mg weekly dose only operates effectively for a few days. Have you thought about the idea of taking your safe high dosage then adding smaller daily increments to keep you at an elevated level a little longer? Taking into account the Rapamycin half-life, this could mean a 5 day high of approx. 8mg if you dosed 8mg x2 x2 x2 x2.

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#16

@JazzMann Very good question, and a daily dosing had crossed my mind. However, I want to use another senomorphic, Taurine, and Taurine cancels out Rapamycins autophagic effects. So I take my large Rapamycin doses on Saturday and start taking Taurine on Tuesday until the end of the week and then repeat. I am hoping for the best of both worlds.

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#17

@DeStrider An important thought. This since I take large doses of Taurine and I wonder where to find research indicating that taurine cancel out the effects for rapamycin?

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#18

The paper is here

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#19

I start with a mechanistic approach.

Rapamycin helps by encouraging autophagy.

Rapamycin causes difficulties by inhibiting cell division.

We definitely don’t want autophagy all of the time. Hence I conclude to have large doses of Rapamycin at a frequency such that most of the time it is too low to have much of an effect.

At the moment I am using 6mg with an accelerator (last time Pomegranate, and probably next time Pomegranate), but every 21 days.

I may increase the dose and also reduce the frequency, but for the moment I want to have the balance in the direction of Rapamycin being more active.

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#20

Yes, I also take Taurine but it may be an occasional approach to consider. Good luck!

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#21

The risk of adding one supplement/drug to another, to another … each with independent sensible evidence, but in isolation is a serious problem. We saw the same thing AKG and NAD boosting medications simultaneously dosed with the wormbot.

It’ll be an unfortunate irony when many of us end up finding out that we are taking things that when taken together net us zero or harm, when had we simply been more limited in what we take, we’d have had benefit.

This is the worry with stacks like Bryan Johnson takes … each for a good reason … but might have a net of zero when had he just taken 5 items, carefully selected, he’d been way better off?

I’m continuing to decrease the number of things I take, or taking something for a short duration for a really specific reason, or cycling rather than having a stack of things all the time.

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#22

For targeting the brain the high peak dose approach may be a way to overcome the BBB yet another approach (for animals) is discussed in the topic Intranasal Rapamycin Lessens Alzheimer-like Cognitive Decline in a Mouse Model of Down Syndrome - #6 by MAC.

The effects that we look for require different plasma levels for different organs early research in marmosets has shows. Fat tissue getting lower concentrations then other at the same plasma levels. Most likely because intracellular processes negatively influence binding of rapamycin to mTor1 I suppose

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#23

This is why I like to start with a mechanistic thesis. It allows at least a thought as to what have synergistic and what have antagonistic effects.

Also I tend to run with a configuration to end at a point when I do another blood test. That allows me to compare weeks and retry configurations that seem to have better outcomes.

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#24

I can find no studies, but we deduce that it has an effect because
taurine is an amino acid derivative, and amino acids are known to influence mTORC1 activation.

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#25

I have been wondering about the efficacy of rapamycin dosing similar to the dasatinib + quercetin. Any thoughts on higher dose, monthly rapamycin protocol?

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#26

I don’t have enough information in your question to answer it. What is a higher dose? What is the “dasatinib + quercetin”?

#27

See:

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#28

Not all amino acids, specifically branched chain aa appear to have the predominant affect on mtorc1 activation. Not sure where the statement that taurine activates mtorc1 derives its basis, it’s not a branched chain amino acid. Does someone have a reference?

#29

Perhaps this one:

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#30

I prescribe Sirolimus for my patients in our Longevity Program. I have them check a blood level 90 minutes after ingestion. I am satisfied with a blood level in the upper quartile of the therapeutic range.
I think the conversation would be more meaningful if it was based on therapeutic blood levels after dosing rather than relying on ‘feelings’ and symptoms only.

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#31

Taking blood levels is always the best. However, not everyone in the world has access to this. It would be better to use blood results to determine the ideal dosage. However do we know the blood concentration of Rapamycin that will guarantee longevity?

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#32

Where did the “therapeutic range” come from?

I’d be interested in knowing if I was taking too little to do any good. However, I wouldn’t take more, I’d quit all together if I knew I needed to take more. The side effects would be too great. But I already am getting some short term health benefits (allergies gone, fewer illnesses, no joint pain)

I’d be interested in knowing that I’m taking too much to avoid damaging my health. I am tracking my blood markers frequently for such evidence but I’d rather use the therapeutic range to tell me that, if it can. I didn’t think anyone knew enough about rapamycin for such a test to help me.

What can you tell me?

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