Experiences starting Rapamycin for first time

CRP is pretty good (if it is per litre rather than decilitre).

Creatinine is hard to get a good measure of as it metabolises in Blood, but neither it nor ALP look problematic. However, I would think there is room for improvement with both of them.

Levine uses the logarithm of the CRP figure.

I intend putting together a good database of research into age linked variations in biomarkers which will make assessing these things easier, but I have not managed to start that yet.

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"I went to the pub had two pints of cider and ate two packets of dry roast peanuts. (that was after a salad in a restaurant with 0.5l of red wine and 2 pints of lager)":yum::joy:
Living a long time isn’t everything.

From Auntie Mame: " Yes! Life is a banquet and most poor suckers are starving to death!"
Half of the people, or more on this forum are saying; OMG
If what you are doing makes you happy I am not going to criticize.

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Over the past 6 years I have moved from someone who is a regular heavy drinker to someone who is an intermittent heavy drinker and my biomarkers have improved. Obviously reducing alcohol does help, but to me it is quite clear looking at the biomarkers that biochemical damage done by alcohol can substantially be reversed. Over use of alcohol, however, is at times fatal.

I have now got a lab that can measure my CRP levels and they are now 0.17mg/L - this lab’s limit is 0.16mg/L so if I get CRP below that then they just say under 0.16mg/L, but at least they could answer the question. When I have asked other labs what their minimum was I tended not to get an answer.

I didn’t have my usual sunday drinks yesterday, but the benefit is a new low in my weight. Interestingly sometimes I sleep more soundly with alcohol and sometimes I don’t although the quality of sleep is better without alcohol. It does mean, however, that sometimes when I sleep drunk the additional sleep means I am not tired the next day. Sometimes when I sleep without drinking the sleep is too short and I need a nap at 2pm.

I started on looking at how to improve biochemistry because of insomnia and I am in a much better state now than I used to be.

Incidentally I wish I had known when I was younger that Pantethine reduces the effect of Acetaldehyde by metabolising it into Acetate more rapidly. Alcphol is initially metabolised into Acetaldehyde and that is what tends to do the harm.

If I drink for a number of days in sequence then my resting heart rate (calculated by fitbit which I think has a lag effect in its algorithm) increases each day and can move up from the low 50s to the mid 60s. In fact the average heart rate when sleeping (drunk) jumps by about 10bpm although the vasodilation effect reduces both systolic and diastolic bp.

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Thanks for your comments John, how would you suggest I go about improving them?

I took 2mg on Sunday, which is my 3rd dose. No side effects on Sunday, but on Monday had the buzzing again and tingling in my tongue.
Just went for a run at 7am this morning and my legs felt like lead. I thought that was odd. Also last week after going for a run my Garmin dropped my VO2Max from 51 where its been for 1.5 years to 50. I was thinking Rapamycin was going to make my fitness go up, but so far (unless its a coincidence) it appears to be going down!

Perhaps its early days - only been taking a 1-2mg dose for 3 weeks now.

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I really don’t think that 1 or 2mg dosing once per week is going to affect much, for most people. And I’m sure a 1 point variation in the garmin VO2Max is in the noise level (I doubt its that accurate to begin with, compared to a treadmill/physiology lab measure: How Accurate Is Garmin VO2 Max?

I would track things over 6 months to get a read on how things are going for you, and not jump to any conclusions at low doses, over short periods.

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Can you please explain what this means?

It may be that Rapamycin in isolation achieves this. I don’t know. I am running a small protocol experiment which is detailed here:

I am still open to having new people join it (in small numbers), but people need to be committed to doing blood tests from time to time - not weekly, but more frequently than annually. It is also rather complicated.

My Garmin reading has been constant for 18 months - odd it just changed. But you’re right - from a statistical point of view it’s certainly too early to draw any valid conclusions. :slight_smile:

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Carotenoid intake can increase blood albumin levels. So things like bell peppers, carrots or sweet potatoes eaten regularly can help.

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Where is your evidence of carotenoid intake being able to increase albumin levels? I don’t think it does so at all. If you’re thinking about Mike Lustgarten’s personal experience where he found that his beta-carotene intake was positively correlated with his albumin levels, that’s just a weak anecdote that doesn’t say whether it’s a cause and effect relationship or whether the effect was caused by the carotenes or something else correlated with eating them.

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I’ve been slowly increasing my sirolimus does to 20mg every 2 weeks. Finally got a blood test last week - 2-3 hrs after taking the tablets - and results were 34ug/L. However, not sure if this is high or about right. Is there any information on the ideal ‘peak’ level to aim for? (I’m 53 with a relatively high CVD risk)

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Kevin,

We really have no idea about what the “right” blood levels for rapamycin are for longevity… so while its interesting (and that is a very high number compared to most applications / uses of rapamycin, other than cancer treatments), it really doesn’t tell us that much.

I think its actually more useful to have the “trough” level of rapamycin, which would require a blood test just before you take the next dose of rapamycin. Its generally believed that its the trough levels of rapamycin the drive the negative side effects of rapamycin - so you want it as low as possible, to minimize risks of side effects.

I hope you’re also doing regular blood testing for lipid levels and blood sugar levels to make sure you’re not getting disregulation in those areas from the rapamycin.

I recommend you read this thread, if you haven’t already: How to get a Rapamycin (sirolimus) Blood Level Test

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Thanks RapAdmin,

Yes, I was wondering if it was the trough that was perhaps more important, ensuring a low enough dose to not activate mTOR 2.

I know Dr Green has suggested to go for 5 halvings from the peak, and I know the minimum trough value that transplant patients are meant keep above is 5ng/mL. Presumably this is because at least 5ng/mL is required to keep mTOR2 activated (which is what a transplant patient wants).

Allowing for some graduation this suggests to me you’d want well under 5ng/mL for the trough for anti-aging e.g. <1ng/mL.

On that logic I’m puzzled that 6mg weekly seems to be the ‘standard’ dosing.

I took 20mg and got 34ng/mL (no grapefruit juice). This suggests (for me at least) 1.7ng/mL per 1mg.

So (if the dose to blood level works linearly) 6mg would give (me at least) a peak level of 10.2 ng/mL.

I understand half-life of sirolimus is considered to be about 60 hours (although some have suggested could be 80 hours in non-transplant patients). This means 7 days would give 2.8 half-lives, which means a trough of 14% peak levels. If peak levels were 10.2 then this gives a trough of 1.5 ng/mL. This is below 5ng/mL, but not much below and doesn’t leave much room for error. For example if the half-life is actually 80 hrs the trough will be 2.4ng/mL.

If someone actually takes 10mg a week (as I understood nearly 10% of survey respondents said they did) then the troughs would be 2.5ng/mL (or 4ng/mL with 80 hrs half-life). Very close to the level for keeping mTOR2 activated.

However, if you were to take 12mg (or 20mg) fortnightly, the trough changes dramatically to 0.4ng/mL (instead of 1.5ng/mL) and in the worst case above, to 0.7ng/mL (instead of 2.5ng/mL).

This seems a much safer ‘stop activating mTOR2’ level to me.

2 weeks is the only way to get Dr Green’s recommended 5 halvings (5.6 at 60 hrs, 4.2 at 80 hrs).

Of course, perhaps my blood conversion level of 1.7ng/mL per 1mg of sirolimus is unusually high.

Right there with you Kevin. I’m puzzled as well about the weekly dose.

I use GFJ and got a peak of 27, tested after 12 days (if I remember right) and got a trough of 2. I did use 12 days for awhile, also used 10 days for awhile and this is where I got in trouble with lipids and fasting glucose. 2 weeks works great for me with my lipids now normal. I’m taking pioglitazone (has almost no effect yet), but the only thing I’ve found that works on my morning glucose is empagliflozin.

One way I found to increase AUC is to take a dose after 8 hours of another mg with GFJ. It puts the peak back up where it was and really the 2 week interval still gets you down to less than 1. I only did this for a couple times, but got no side effects and I still think it was a good idea.

All of this is speculative since there is really no proof. So wrecking lipids or glucose seems like a bad idea. Good luck,

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I’d be really careful with interpreting this data. Measuring blood rapamycin levels shortly after taking the medicine is, I think, really hard. Look at how quickly the blood level peaks and then falls off. Its like catching a falling knife. If you repeated the test and varied the time just 15 minutes you could get radically different numbers. And the research suggests the blood levels and half lifes vary quite a bit person to person, and also depending on what you’re ingesting before taking the medicine.

Note: the above data is from this study: Pharmacokenetics and Safety of a Single Dose of Rapamycin (sirolimus) in Healthy Males

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Hmm, thats a fair point. Using an average half life estimate to calculate expected future blood concentration is only valid if the decay function is an true exponential.

In fact it appears to be steeper than an exponential, as simple exponential would show as a straight line on this logarithmic chart.

In other words the half life appears to be just a few hours initially, then gets longer and longer.

I wonder if anyone has tried to fit a curve to this.

Ultimately this suggests, as you imply, the only way to know what the trough is reliably will be to measure it.

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Agree, which is why I thought it prudent to go for 14days once I wanted to up my dose.

Am thinking I’d want a trough of under 1 if possible.

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On the day I take my Rapa, I sometimes have less exercise tolerance. The day after I feel like I can run a marathon!

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You cannot make these estimations based on your blood test. First of all, you don’t know what your peak was because when you take a blood test just a few hours after dosing you have no idea how close you were to the peak. Your peak might have been a lot higher than 24 µg/L. Secondly, even if you knew your peak level, you can’t use that to calculate your levels later because the drop is way faster than the elimination half-life in the beginning. You have to measure at least 24 hours after dosing to get meaningful data. 48 hours after dosing would be even better.

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