GetHealthspan - new Sirolimus level testing

I found out some time ago that https://gethealthspan.com has a test to measure Sirolimus levels in the blood. It costs me $25. The more interesting thing about it is that they analyze your results to help you determine if the level in your blood is therapeutic. I found their classification fascinating. I don’t know how they came up with them. Here they are.

For peak level of Sirolimus

Testing should occur after 2-4 hours. Here are the possible values:

  • less than 10 ng/ml: Insufficient dosage

  • 10-20: optimal dosage

  • more than 20: higher than necessary, might lead to side effects

For through levels of Sirolimus

Testing should occur 24-48 hours before your next dose. Possible values:

  • less than 1 ng/ml: optimal value

  • more than 1: you might want to wait longer before your next dose

For mid-cycle levels of Sirolimus

This one I was not famillair with. The idea is to measure how fast the drug is being cleared from your system. Your peak value might be fine, but if you clear the drug too fast, you might miss some benefits of the drug. This is scheduled 72 hours after your initial dosage

Possible values:

  • less than 3 ng/ml: the drug has cleared from your system too fast

  • more than 3: optimal value

So it seems that the protocol above makes a good compromise between a relatively high peak (10-20 ng/ml after 4 hours), and moderate AUC (3+ ng/ml after 72 hours).

Using these guidelines, I found out that I clear Sirolimus much faster than I expected: I spent several years at 3 mg per week or more, but to obtain the numbers in the therapeutic ranges outlined above, I had to go up to 10 mg per week.

This does highlight the fact that talking about dosage in mg can be misleading, and for people that have access to it, talking about ng/ml might be more accurate. Maybe the guidelines could serve as a protocol for future studies.

I would be curious to know what people think of this protocol described above, and where they think these numbers they in the protocol came from.

I’ve attached my results as a PDF

Healthspan _ Patient Portal.pdf (62.6 KB)

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I think their protocol is mostly good - BUT I think at 72 hrs having >3 ng/mL does result in some degree of immunosuppression, and if essentially you have a level of 3.7 they’d be happy - I’d not be happy unless your dosing interval were >7 days. As having 50% of the week with levels >3 ng/mL means you’re having 50% of the time with more susceptability to things caused by immunosuppression.
I personally goal for no more than 1/3rd of the time with levels >3 ng/mL.
For individuals dosing on the 72 hr level, I’d be interested to see what their rate of infection is compared to controls. I think if they adjust their goal to a level just over 3 at 48 hours, that might be sensible for weekly dosing.

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This is great - but I can’t find it on their site when I look at labs they offer: All in One Longevity Lab Testing

How did you order it?
Do they only offer it to people who are getting their rapamycin from them?

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Here is the direct link to it : Rapamycin Bioavailability Panel

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I’d be interested at how they came up with this number of 3ng/ml for mid cycles.

I think @Daniel_Tawfik is one of the people working on over there. @Daniel_Tawfik do you have any insights on the dosage ?

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Can’t seem to just order the test. They take you through a whole process of testing, monitoring, sending meds, etc. $360/3mo.

FWIW, I was able to get the test ordered for $25. Website was a bit difficult to figure out

DrFraser, Curious your opinion. I did a sirolimus lab 2.5 hours after my dose of 10 mg of rapamycin and. my readings were 28.5 (High) Units ng/mL.

The Reference Interval 3.0-20.0.
I’m assuming I should lower my dose? To 8 mg?

I did the same lab 72 hours after my initial dose and I"m waiting those results and will be doing the final lab a few hours before my next dose. Thanks Dr. F and anyone else for your input.

Essentially you don’t have a full picture of things when you do an early level. This represents absorption of the drug, but it is extensively distributed into tissues. So that 28.5 once distributed might be a 6-8 ng/mL. This is why I suggest doing a 20 hour level, and if really pinning things down, repeat 48 hours after that to look at metabolic half life.

I’m happy with most of my patients just doing a 20 hour level as we know what the T1/2 looks like on single doses for most people. I’m mostly seeing from mid 20’s to mid 30’s hours as T1/2. So if I have someone with a level of 6 at 20 hours, this is pretty good for weekly dosing, if I have someone at 9 then intervals would go to 10-12 days (or drop the dose).

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Thanks for the reply. Can you clarify with 20 hours and 48 hours? You mean 20 hours and 48 hours after the initial dose?

Chris

Sorry, let me clarify, getting a level 20 hours after initial dose (and if a decent therapeutic level as these often turn around in less than 48 hours) then doing a second level in order to look at metabolic half life at 48 hours after the first blood draw.

Let me give an illustrative example.

My level at 20 hours was 9.5 ng/mL, but I’m on a longer dosing interval as I’m pushing things a bit higher as I have an ApoE4. 48 hours after that blood draw my level was 4.2 ng/mL.

I don’t think we need to be overly precise, but talking in rounded figures, 44% of the rapamycin still active 48 hours after (4.2/9.5). So I’ve gone through a metabolic half life and a bit more in 48 hours. So I’d roughly think my half life is maybe give or take 42 hours.

So from this I’d then look at the 4.2 ng/mL and figure out when this is going to be at 3.0 ng/mL as it is that segment of time, from dosing to 3.0 ng/mL that I think rapamycin has enough activity to strongly inhibit mTORC1 in a meaningful fashion.

So we’d estimate in 42 hours after the 2nd blood draw my 4.2 ng/mL would be 2.1 ng/mL as we’d have another half life. So I’d guess 24 hours or so from the 2nd blood draw I’d be >= 3.0 ng/mL.

So doing the math 20 hrs + 48 hrs + 24 hrs =92 hrs (3.8 days) having solid mTORC1 inhibition.

I’ve been goaling most people I treat, who opt to measure levels, to have no more than ~30% of the time above 3.0 ng/mL, and then 70% in recovery. So think this roughly works out to a dosing interval of no closer than 12 days.

That is my thought process and how I use levels.

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Thank you for this explanation. Extremely helpful.

Could you share what dose you were taking when you got these blood levels?

Yes sorry that was on another thread. 4 mg with 8 oz of fresh GFJ 3 hours prior and 4 oz at time of taking it. Use the same brand each time. So equivalent of 12 mg, using RapaPro brand. I usually dose every 12 days.

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I just got my second of three sirolimus labs back. This one was 72 hours after the initial dose. My result was 3.1 ng/ml. Recall that the result was 28.5 ng/ml after 2.5 to 3 hours after my initial dose. According to the GetHealthspan numbers, this may suggest that my dose is ok. Thoughts?

If you are okay having solid mTOR inhibition for a bit over 3/7’s of the week? I would usually go for a 9-10 day interval on that dosing with those levels to allow better recovery.

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@DrFraser Jumping in to the conversation…

Is the rationale for not going for an even longer interval (say 2-3 weeks) so that more doses can be employed over time? Is this age related? The older patient is in more of a hurry to have an effect but a younger patient can be more patient (longer interval)?

I’m happy with people going longer, but I don’t like seeing >1/3rd of the time with a sirolimus level>3. I think we will see increased complications. None of the trials done for safety in regard to longevity dosing of sirolimus have used sufficient dose to get levels this high, except, I think the short one where they looked a premedicating the influenza vaccine and getting a bigger T cell response. With that trial, it was short duration, I think for the long haul you want your humoral immunity to be pretty good most of the time, and there seems to be a benefit to cycling from mTORC1 inhibition to not having much inhibition.
As I’m currently adding some items to my regimen I’m prolonging my intervals to 14 days - by my levels, I’d be fine to do every 12 days.
I appreciate Dr. Green made a significant statement, but I’m not sure there is any clear scientific evidence for it, but I’m sure he had a logical reason for it, around increasing dose with age. Well to a certain degree, but the patient’s I’ve had join my practice, who previously were under his care - I’ve not had any on more than 6 mg/week. Often these individuals are in their 70’s, so I’m not see the dose intensification discussed with age in actual practice.
I haven’t taken on the older patient doing anything different - it’s more risk profile - if ApoE4’s, more interested in being a bit more aggressive dosing, which then has me prolong the interval between dosing.
So far this has been safe. The only potential adverse reaction was an upper eyelid infection, which who knows if it is causative or not. However, I need more data and time to get a better sense of risk with this dosing regimen, but so far, I’ve been happy with the safety profile.

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