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My fasting protocol using rapamycin, dasatinib, and azithromycin

fasting dasatinib senolytics rapamycin quercetin azithromycin longevity fmd autophagy igf1

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#1 Thingsvarious

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Posted 24 March 2021 - 08:36 AM


One of my goals is to live beyond the years of 200. I feel this goal is quite realistic even with our currently available methods. Aging is certainly very multifactorial and has to be targeted from multiple angles.

 

Here I want to share with you my personal fasting regimen for longevity.

 

I think longer fasts are incredibly healthy (and they might even be the next health revolution). The temporary uncomfortableness is nothing compared to the metabolic, health, and longevity benefits it gives us. Firstly, longer fasts (36h +) are a powerful driver of fat adaptation and thus promote metabolic flexibility. Secondly, next to being great for metabolic health (e.g. fat-adaptation, autophagy, stem cell activation) fasting also has powerful psychological benefits (e.g. developing self-discipline, opting for the hard things which makes me proud of myself).

 

Therefore I do a 5-day fasting-mimicking diet (FMD) four times per year. I do this to foster self-discipline, activate autophagy, tune-up my metabolic flexibility by having gene expression induced towards a more fat-adapted state, to cycle IGF-1 levels, and to clean out senescent cells.

  • For fostering self-discipline I simply do not eat.

  • For “boosting” autophagy I take an additional 8mg of rapamycin 1 day before starting the fast. For more info on why I take rapamycin, how I take it, and its benefits, see the article linked below.

  • For why I cycle my IGF-1 levels, how that activates stem cell proliferation, and how that gives me the best of both worlds, read the respective Section here: How To Replace Growth Hormone.

  • For cleaning out senescent cells: After day 3, nutrients and growth factors (e.g. insulin, IGF-1) are low, autophagy is ramped up, and mTOR is mostly inhibited (both from the fasting + the rapamycin). At this point, cells are highly sensitive. Therefore, I take a cocktail of senolytic drugs on days 3, 4, 5, and 6 -hoping to induce a body-wide clearance of senescent cells (which is much more effective in an mTOR-inhibited state). My senolytic regimen is comprised of the tyrosine kinase inhibitor dasatinib (2x 70mg/d) + the flavonoid quercetin (500mg 3x/d) + the antibiotic azithromycin (125mg/d). The most potent of these senolytics is certainly dasatinib. My guess is that over 90% of the senolytic effects are coming from dasatinib, while perhaps 10% or less are coming from the combined use of quercetin + azithromycin. I am aware that dasatinib does target certain cell types more than others (e.g. adipocytes > fibroblasts) while leaving some tissues quite untouched, but, unfortunately, no other senolytic agent is clinically tested and most of them are only available in a research setting (e.g. MDM2-inhibitors, Bcl2-inhibitors).

  • In addition, I also take 1800mg/d of extended-release potassium tablets, 600mg elemental magnesium, 200mg calcium, and salt.

  • I also take some supplements. For my exact supplement protocol, see here: Supplements Everyone Should Take.

While all this might sound extreme, I have performed this protocol quite a few times - without any (significant) adverse effects other than transient thrombocytopenia and a few mouth ulcers.

 

I do not fast for longer than 5 days because with the use of rapamycin and in my already fat-adapted state, my metabolic state is likely already at a “day-3-level” on day 1. Furthermore, I do not compromise my peripheral thyroid sensitivity too much. I opt to do a fasting-mimicking “fast” instead of a complete fast because I am already quite low in body-fat, and the fatty acids my cells need to use for energy have to come from somewhere.

 

I usually consume around 800kcal/d of nut butters (coconut, peanut, hazelnut). Nut butters have negligible glycemic and insulin indices, essentially keeping my insulin levels unchanged. The main benefits of fasting (perhaps 80% or so) come from having insulin levels reduced to very low levels anyway, so in my opinion, a complete fast is unnecessary and/or the difficulty vs. benefit ratio is not worth it. Furthermore, fasting-mimicking makes the fast a lot easier and allows me to keep up with my normal level of productivity (in fact, productivity is much higher during these five days).

 

For more info on my general approach to diet, and the diet-mimicking drugs (metformin, SGLT2-inhibitors, rapamycin, acarbose) I use or have experimented with, how I take them, etc. see Note #3 in the appendix of A Diet That Works Well For Everyone

 

What do you guys think of this protocol? Feedback appreciated.


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#2 pamojja

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Posted 24 March 2021 - 10:56 AM

In addition, I also take 1800mg/d of extended-release potassium tablets,

 

Potassium in supplements is limited to 99 mg per cap, because to much of it sitting in one place can damage the stomach walls. Prescription Potassium is higher dose but even riskier because of that. The safe way to supplement high doses of Potassium is using bulk-powders (Potassium citrate, -bicarbonate, or/and -chloride) well disolved in a glass of water, taken throughout the day.

 

Personally did a water-only fast for 21 days at young age, more for spiritual reasons, and not monitoring blood-markers. Find complete fasting easier, since any hunger ceases after 3 days. With chronic diseases 20 years later (PAD, prediabetes..) I again tried a 1 week fast. To my surprise this now even worsened my insulin resistance (now monitoring) for the next year. But maybe only a coincidental association, and insulin resistance anyway worsening despite.

 

 


Edited by pamojja, 24 March 2021 - 11:05 AM.

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#3 Thingsvarious

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Posted 27 March 2021 - 04:49 PM

Potassium in supplements is limited to 99 mg per cap, because to much of it sitting in one place can damage the stomach walls. Prescription Potassium is higher dose but even riskier because of that. The safe way to supplement high doses of Potassium is using bulk-powders (Potassium citrate, -bicarbonate, or/and -chloride) well disolved in a glass of water, taken throughout the day.

 

Personally did a water-only fast for 21 days at young age, more for spiritual reasons, and not monitoring blood-markers. Find complete fasting easier, since any hunger ceases after 3 days. With chronic diseases 20 years later (PAD, prediabetes..) I again tried a 1 week fast. To my surprise this now even worsened my insulin resistance (now monitoring) for the next year. But maybe only a coincidental association, and insulin resistance anyway worsening despite.

 

Extended-release potassium (prescription) does not damage the intestinal lining. Furthermore, with the extended release there is no "risk" as the risk pertains mostly to cardiac conductivitiy issues occurring whenever potassium levels change too fasat.

 

Fasting does worsen insulin resistance in the short term (fatty acids in the plasma), however it should improve it over the long term



#4 Thingsvarious

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Posted 03 April 2021 - 11:42 AM

I plan on doing my next 5d FMD in 1 week from now. 

This time I might change the peanut butter to 99% dark chocolate. Furthermore, I will also add in the azithromycin for the first time.

We will see how things go



#5 Mind

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Posted 04 April 2021 - 10:12 AM

I was considering something like this as well - fasting, but with essential nutrients. Something like CRON but more extreme for 3 to 5 days. Consuming some beneficial supplements, maybe fiber and collagen, a tiny amount of beneficial fat, etc...



#6 Thingsvarious

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Posted 08 April 2021 - 02:28 PM

I was considering something like this as well - fasting, but with essential nutrients. Something like CRON but more extreme for 3 to 5 days. Consuming some beneficial supplements, maybe fiber and collagen, a tiny amount of beneficial fat, etc...

So a very similar approach to what I have. I am currently on my day 4 of my quarterly FMD. Dasatinib does make you feel like shit though lol for a few hours after taking it



#7 OlderThanThou2

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Posted 18 April 2021 - 03:43 PM

In regards to gut bacteria, can fasting induce autophagy in it and make it more healthy? How long would a fasting need to be for that? On another hand would it be good to kill all gut bacteria by doing a long fast and rebuild the microbiome after? Also what happens to the gut wall? Does fasting make it more porous or the reverse?

 

I've heard several really bad stories with long fasts, personaly I wouldn't do it. I wonder if initially in the first days, the body is not capable of getting enough energy from fat, and catabolizing enough muscle does not make the body continue to function, but after some time, there's not enough FFAs from lipolysis since BF is decreasing quickly, and enough amino acids made available from muscle catabolism, but then some tissues begin to encounter significant problems. There is something called malnutrition and dying from hunger.



#8 Thingsvarious

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Posted 24 April 2021 - 02:50 AM

In regards to gut bacteria, can fasting induce autophagy in it and make it more healthy? How long would a fasting need to be for that? On another hand would it be good to kill all gut bacteria by doing a long fast and rebuild the microbiome after? Also what happens to the gut wall? Does fasting make it more porous or the reverse?

 

I've heard several really bad stories with long fasts, personaly I wouldn't do it. I wonder if initially in the first days, the body is not capable of getting enough energy from fat, and catabolizing enough muscle does not make the body continue to function, but after some time, there's not enough FFAs from lipolysis since BF is decreasing quickly, and enough amino acids made available from muscle catabolism, but then some tissues begin to encounter significant problems. There is something called malnutrition and dying from hunger.

I´ll take roxithromycin during my fast so I´ll kill all my gut bacteria anyway.

Fasting does induce some autophagy, however at least a 7day water only fast for that to significantly happen (without rapamycin as a cruth).

Depends on how bad your gut health is. Personally, dasatinib certainly makes the gut wall more porous for a few days.

 

This only happens if you have zero body fat or extremely insulin insensitive.







Also tagged with one or more of these keywords: fasting, dasatinib, senolytics, rapamycin, quercetin, azithromycin, longevity, fmd, autophagy, igf1

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