Yet another rapalog (37 M)

Background:

37M, generally in good health. Exercise regularly (weights and cardio) and eat a moderate low-carb(ish) diet. Not much to comment on here.

Existing supplements:

Vitamin D - 5000iu 3x // week during winter
Acetyl-Carnitine — 1-2g, 5x per week
KSM-66 ashwagandha — 600mg 4-5x per week (or as needed for stress)
NMN - 250mg-500mg on occasion when I need an energy boost. I do find this works for me acutely better than chronically.

I had started astaxanthin again but dropped it as I didn’t want to change any variables from what I had been taking previously.

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Week 1 (Monday, Dec 5):

I’m writing this retrospectively, I took 2mg with 6mg piperine (inhibitor of CYP3A4). I noticed some fatigue later in the day and took a nap. Felt great the next several days.

Perhaps noticing some increased soreness from exercise in the days following. Not quite as much energy in the gym for a day or two.

Overall pretty mild effects, think I maybe psyched myself out.


Week 2 (December 12):

Took 5mg this morning with 12mg piperine. Felt more comfortable bumping the dosage after I didn’t really react to 2mg. Might switch to grapefruit juice but I hate the stuff and I have piperine on hand. It’s a bit unclear to me how much the piperine increases the absorption though, I’d rather have some concrete numbers. Probably best to get a blood level sirolimus test at some point.

Noticing mild fatigue again. Really seems pretty mild though, if I didn’t know that I took rapa today I probably wouldn’t have noticed much.

Will continue taking it at this dosage (5mg // week, likely with some sort of absorption enhancer).

Bloodwork to follow in the next couple weeks. I’ve had no side effects thus far, but it’s quite early so I’ll update if that changes.

Cheers,


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Thanks for this. I’m starting soon as well (40M). I just need to bite the bullet and get my blood work done beforehand. I abhor needles lol.

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Thank you for sharing these details. I’ve also noticed mild fatigue in the gym for 2-3 days after dosage. Grapefruit juice has not interested me because of the variability between brands of juice, varieties of grapefruits, and variable dosage if you’re actually eating a grapefruit. Piperine sounds like a potentially better choice. If you get a blood test on the dosage with piperine I’ll be interested to hear the results. How did you arrive at the rapa::piperine ratio of 2::6 and 5::12? Do you take your dose with high fat too? Best of luck going forward!

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Quercetin is another potent inhibitor of CYP3A4 if you want another option. From what I’ve quickly scanned, it should be nearly as effective as grapefruit juice. 55% inhibition compared to 67% from bergapten, the flavonoid in grapefruit juice which inhibits CPY3A4.

GFJ may be more potent though because it has two flavonoids which inhibit that enzyme, but it’s not as standardized as a well sourced quercetin supplement.

https://sites.ualberta.ca/~csps/JPPS4(3)/S.Wanwimolruk/grapefruit.htm

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Grapefruit juice is supposed to be taken 2-4 hours before rapa dosage and pagans along with the dosage, as I understand it.

Would it be your thought that Quercetin should be taken in the same window of 2-4 hours before rapa dosage? Not looking for medical advice, just your personal opinion.

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IMO, yes 1-2 hours before, probably with some food so the powder can disperse from the capsules adequately. That’s just a guess.

edt definitely with food or some kind of fat because it’s not water soluble.

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I mix it with EVOO for absorption.

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First, to respond to some previous questions:

  1. I take rapamycin with breakfast, which typically includes some almond butter or fat source. Not an excessive amount, but it’s with a meal.

  2. Regarding piperine, I wish I had better data, but the reality is we’re flying blind with any sort of absorption enhancers unless we get a blood test (which I do plan to do at some point). If rapamycin supply is unlimited, I think it’s best to titrate the dosage of rapa itself as opposed to tinkering with piperine // grapefruit.

  3. I’m taking piperine concurrently with the meal // sirolimus, however I may switch to taking it 30-60 minutes prior.

Onto the log:

Week 3 (December 19):

Took 5mg about 30 minutes ago with 30mg piperine. My log is a bit clouded the last week as I’ve had two issues come up:

  1. I had a minor cold which started around the beginning last week’s dosage (mostly gone now)

  2. Contrary to many people’s experiences here, I exacerbated an existing injury and have been unable to weight train as I’d like. I have been doing some cardio, despite being slightly sick I was able to put up some good numbers for that relative to my recent history.

So my health has been marginally worse over the past week, although it’s very likely coincidental. I’ve noticed zero side effects related to skin, mouth sores, etc. What I have noticed is a sense of malaise about 3-6 hours after dosing, which then turns into a sort of energy // stimulation. It’s still very early for me to really be sure about anything though, the effects are far milder than I had originally anticipated. I’ll update as to whether the acute effects of the 3rd dose match the previous 2 doses. Perhaps my body is just adjusting the drug.

The plan is to continue on this dosage for a while (30mg piperine // 5mg rapa) and see how things go. TLDR is I feel good, no major sides good or bad.

Edit // Quick update:

No real fatigue today. Did some cardio HIIT (not that intense, but still reasonably difficult and winded) and felt great. Could’ve gone harder but didn’t want to do too much the same day as rapa until I have more experience with the drug.

I do notice something from acute rapa dosing, it’s just hard to describe. There’s a noticeable anti-inflammatory feeling, and my head feels clear. Maybe a slight blunting of appetite.

Cheers,

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I took 5mg of Sirolimus this morning, along with 30mg piperine and a breakfast containing some fat and protein. This time, the 30mg piperine was taken approximately 20-30 minutes before the meal.

Some notes regarding last week:

Sides:

  1. I have noticed slightly increased flatulence/gas throughout the week. I would say this is the only noticeable side effect so far, and it’s quite mild. I do think it’s possible that it’s related to rapamycin.
  2. Two tiny mouth sores that resolved in a matter of hours. Honestly, if I weren’t looking for mouth sores I probably wouldn’t have even noticed.

Benefits:

  1. My sleep efficiency score (as measured via oura) seems to be improved, particularly days 2-4 after dosing. In general, I am waking less during the night and when I do wake, it’s easier to fall back asleep.
  2. Subjective, but generally feeling pretty great.

Neutral:

  1. I haven’t been lifting (rehabing an injury) but my cardio endurance seems unaffected, even on dosing days. I plan to do HIIT today.
  2. I haven’t seen much in terms of body recomposition, but I haven’t lost much muscle despite not lifting. I actually think it’s plausible there’s almost a muscle preservation to rapa, but this is highly subjective.
  3. I haven’t noticed any restless sleep the first night after dosing as some people have. I have been taking a small amount (0.5 mg) of melatonin on dosing nights just in case however.

Currently Reading:

Link – Faculty Opinions

“Two independent studies used slightly different resistance exercise models in rats and found that rapamycin blocked the early increase in protein synthesis but failed to completely block the late increase in protein synthesis induced by an acute bout of exercise”.

" Previous studies in mice have reported that rapamycin treatment does not protect from denervation-induced atrophy, nor does it exacerbate muscle loss"

“Low-dose rapalog treatment, started at 22 months of age for 6 weeks in Sprague Dawley rats, was able to prevent the loss of mass in some (TA and plantaris) but not all (gastrocnemius) muscles”

I think as others have mentioned it may be appropriate to not engage in resistance training on the day of dosing. It’s interesting to me that chronic MTORC1 activity actually contributes to sarcopenia. Rapa may actually benefit aged muscle. Empirically, at least at the dosages we’ve been experimenting with, muscle mass doesn’t seem to be impaired :slight_smile:

Cheers,

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GoldenCB, I’m not the brightest star in the sky which means you’ve probably already answered my question, but I didn’t see it. Will you elaborate on why you think the above quote is the case? Thanks.

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There’s a lot of theory that rapa could blunt muscle growth due to MToR suppression. In practice it doesn’t seem to be too bad. See this quote again:

“Two independent studies used slightly different resistance exercise models in rats and found that rapamycin blocked the early increase in protein synthesis but failed to completely block the late increase in protein synthesis induced by an acute bout of exercise”

That being said, 30mg piperine + 5mg rapa may be too much for me. I am feeling pretty crappy this week, and my recover from exercise feels particularly poor (tired, muscle cramps, etc).

Will keep experimenting and posting here. Important to try to log and evaluate over the long haul.

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First, before anyone takes my words as being too important — I am a layman and a software engineer by practice. So take everything I say with a grain of salt :joy:.

My guess is that rapamycin blunts mtor even in the presence of amino acids. It’s not as if the mice in the longevity studies were starved. So I don’t think exercise and/or protein around rapa defeats the purpose at all. Rapa also has a tremendously long half life.

The theory is that timing a rest day around rapa dosing could potentially mitigate any issues regarding suppression of muscle building related to resistance training. I’m young, still a bit vain, and want to keep my muscles.

I will say — I think I have two sides so far from rapa, and they are:

  1. increased gas and maybe even a little diarrhea
  2. increases tendency toward muscle cramps (I rarely get these).

Will be decreasing my dose of piperine this coming Monday, and try to titrate 5mg rapa + piperine to a level where empirically it “feels good”.

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Week 5 (Jan 2, 2023)

Despite my previous post, I decided to take 30mg piperine + 5mg rapa yesterday to keep things consistent. The results were fairly unremarkable. I felt a mild fatigue during the day, but nothing else notable. I slept extremely well last night and have noticed no gastro symptoms or otherwise. I feel great this morning.

A noteable difference is I skipped my exercise yesterday, I do think rapa is a sort of stressor on the body, and perhaps the combination of HIIT + rapa + a bit of holiday indulgence last week was too much.


I had bloodwork done on Dec 22, only 3 weeks into rapa. Glucose levels are great (HBA1C was ~4.5), my only concern is a slightly elevated APO-B and LDL. I’m fairly sure I had these prior to rapa as well, and I’ve also put on some weight lately. Going to see if cutting some weight and dropping my meat intake a bit helps with the APO-B numbers.

Cheers,

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Week 6 (Jan 9, 2023)

Last week I felt quite good. I’ve made a few lifestyle modifications in addition to rapa which may cloud the results.

My APO-B came back at 130 which is apparently quite high. Given I’m only 37 this is fairly concerning and something I want to attack aggressively, so I’ve made the following lifestyle modifications:

  1. Decreased meat consumption (1 meal a day of fish/meat, instead of 2). Replaced protein with lentils/low fat yogurt mostly.

  2. Addition of metamucil (psyllium husk), approx 10-20g per day.

I’m also cutting calories a bit with the intention of dropping to 10-12% body fat or so. I’m probably running 17%-20% at the moment. I think cutting body fat will be the largest contribution to lowering APO-B, but we will see.


In any case, I didn’t notice any negative side effects this week. I still have some gas // flatulence but nothing that I can’t attribute to just increased fiber intake // psyllium. I have had some annoying injuries kind of creep back up, but nothing too terrible.

On the positive side, my sleep is good, and I feel a bit more awake /and have more energy during the day. Again, hard to attribute to rapa necessarily, but it doesn’t appear to be hurting anything.


Dosage note — continue to take 5mg rapa. Took 30mg piperine approx 30-60 minutes before rapa with breakfast. I did some cardio this morning prior to dosing as well.

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Week 7 (January 16, 2023)

Last week was a bit mixed. I felt great until about Friday, then was hit with a minor headcold. I have 2 young kids, so getting sick is part of the bag. Lingering headache and some fatigue the last couple days.

Overall I do think I’m noticing a bit more energy compared to pre-rapa. I’ve been waking up earlier and doing some exercise in the morning. Typically I’m the type to need 8 or even 8.5-9 hours of sleep, and many days now I seem to need only 7.5. My sleep quality also appears to be improving a bit as judged by the sleep efficiency in my oura ring.

Some of this may be clouded again by some lifestyle changes, in particular eating a bit less and more plants // slightly less meat. I’m still not experiencing any side effects, although I noticed some transient redness on my shirt borderline this morning after dosing.


Regarding today’s dose, I continued to take 30mg piperine along with 5mg rapa. However I also had a grapefruit lying around, so I had that with breakfast too. I didn’t notice much difference between today’s dose and any other dose, if anything maybe it felt a bit milder. Contrary to my initial experiences, I think I’m noticing an energy boost the day of dosing. But today it’s hard to tell as I’m fighting a cold.

Again it’s all very early – I will say my instinct is that rapa is doing something positive – I seem to be feeling “great” for the few days following dosing and slightly worse into the weekend.

I realize this is all fairly subjective but that’s what you get with a log :sweat_smile:.


Regarding supplementation, I switched things around slightly as well, the stack is now:

Ashwagandha (1-2x per week down from 4-5x)
Psyillium Husk
Astaxanthin (12mg, new. I notice very little from this and I’ve taken it in the past without issue)
Ginseng (new, 5x per week, just seems to make me feel good)
Creating (5g // day, 5-6 days per week. Forget if I mentioned this before, it’s always been there)
Piperine (30mg with rapa 1x // week)
Rapa (5mg // week)

I hope that oral PCSK9 inhibitor comes out soon, as I’d like to stay on rapa while keeping lipids under control and my APO-B is already high prior to rapa. I’m on the fence regarding statins, there’s all this conflicting research out there and I don’t know what to think there.

Cheers,

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An update –

So perhaps it was a bad idea to take rapa (particularly with grapefruit) while at the beginning stages of a cold. I have been much more fatigued than usual over the past several days. What feels like a minor cold seems to be lingering, and my symptoms are substantially worse than my wife as a comparison.

While this could be random, I think next time if I’m experiencing any sort of cold/flu symptoms I will pause dosing until I feel mostly recovered.

I had previously noted a trend towards increased energy in the days following rapa dosing, but this week it seems to be the opposite.

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Week 8 (January 23, 2023)

As mentioned, last week was really rough due to a weird head cold that left me exceptionally fatigued and cloudy. I do think rapa may have something to do with causing the cold to be worse than expected. From now on, if at the beginning stages of an illness, I’ll pause dosing. I’m currently at the very tail end of the cold.

Yesterday, I took 5mg rapa with 1 fresh-squeezed grapefruit and 30mg piperine. This may be a lot, but subjectively I think the grapefruit works much better than piperine at increasing absorption. I’m honestly unsure if the piperine does much. I do plan on getting a blood test at some point.

After dosing I actually felt quite a bit better. The cold was lingering a bit and I felt that rapa may have calmed it down. Perhaps rapa is better used toward the tail end of a cold, to turn off excess inflammation, than at the beginning.

I’m writing this the subsequent morning and continue to feel great. My sleep was refreshing and my head feels clear. This is the feeling I typically get from rapa in the days following dosing, so it’s nice to have it back as it was quite the opposite the prior week.

Not noticing any significant side effects so far. On a positive note, I’m finding it slightly easier to lose some fat. It’s not anything too crazy at the moment, but it feels slightly easier to keep off weight once it’s lost.

Cheers,

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Took 5mg with grapefruit juice (6 oz fresh squeezed) yesterday, skipping the piperine.

Generally noticed very little, it felt like the mildest dose thus far. Compared to say, piperine + grapefruit which was pretty intense in retrospect.

It’s hard to say but I may have underestimated the impact of 30mg piperine. Subjectively, skipping piperine made the dose feel less intense. F

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Overall I continue to feel good. Had some diarrhea last week but hard to tell if that’s a side as my son and wife both got the stomach flu.

Started a probiotic again (visbiome). I’ve used it before and my stools do seem a bit better on it.

Nothing else too notable, hoping the benefits continue long term.

I miss the mild euphoria//energy I had with rapa + piperine + grapefruit, so I’ll likely combine them again next week.

Looking back, side effects are minimal to unclear so far. The most likely sides are looser stools, and a tendency towards muscle cramps, but still evaluating these.

The most likely positive effect is improved sleep and higher, more stable energy.

Cheers,

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