SNK
#180
Very interesting (if true) and very weird also. I don’t know about the absorption part but I have realized that I always default sleeping on my right. Perhaps it my bodies way of emptying the stomach ASAP so I can get a restful sleep.
The vagus nerves on the right and left perform different functions such that lying on the right is more calming.
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I spend ~80% of my time sleeping on my right side. It just seems more comfortable for me, yet every article on the best sleeping position suggests the left side is healthiest.
“Which is the healthiest side to sleep on?
And sleeping on the left side is best because it keeps pressure off internal organs and promotes healthy blood flow.Mar 17, 2023”
Mayo Clinic Minute: What is the best sleeping position? - Mayo Clinic News Network.
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SNK
#183
Are you kidding me (these studies). I literally feel I’m short of breath when sleeping on the left. I could be an aberration.
1 Like
man_li
#184
Eat grapefruit or drink grapefruit juice is not convenient, I just found a company named ‘True Citrus’, they have some products which are crystallized lemon/lime/grapefruit powder.
So I wonder this crystallized grapefruit powder would works or not works? Have anyone tried? Can someone give some advice? Thanks!
You can google ‘True Citrus’ and easily find the product (Amazon available too).
https://www.walmart.com/ip/100-Pack-True-Grapefruit-Sugar-Caffeine-Free-Powdered-Drink-Mix/524174901
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Interesting idea… but I have no idea if it will work or not, and haven’t seen anyone trying something like this yet. It would be great if you could try it and do a blood sirolimus level test afterwards to get a rough idea of if it works or not… How to get a Rapamycin (sirolimus) Blood Level Test
People have tried some similar things - like using the naringen supplement which may also work: Naringin instead of Grapefruit Juice
I recommend you read the entire Grapefruit and Rapamycin thread too - lots of good info and experiences: Rapamycin and Grapefruit Juice
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man_li
#186
I have just started taking rapamycin yesterday. My dose is 1 mg/week now. I will increase 1 mg per week, and my target is 6mg/week. I am not live in US or Europe, there is no agency to do a blood sirolimus level test.
I also found a product named “Senolytic Activator” from LifeExtension company. It said to be taken once a week. So I think it’s proper to combine with rapamycin. And ‘Senolytic Activator’ ingredients like quercetin & apigenin which both can inhabit CYP3A4, this should lift the bio-availability of rapamycin.
https://www.lifeextension.com/vitamins-supplements/item02301/senolytic-activator
I want to take rapamycin together with ‘Life Extension’ Senolytic Activator & ‘True Citrus’ grapefruit powder, both once a week)
Does anyone think it’s a good idea? Thanks!
1 Like
man_li
#187
According to this post, I think Senolytic is also important.
@man_li Taking Rapamycin with a senolytic activator should be fine. If you are going to take a grapefruit product, make sure you take it 1-4 hours before the Rapamycin. However I do not know if your product will work in this regard. Good luck!
Remember that if you experience any unusual side effects, stop what you are doing and reevaluate.
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CTStan
#189
Unless you can determine that the grapefruit powder has furanocoumarins content equivalent to that in grapefruit juice, you cant expect it to be an equivalent bioavailability enhancer as grapefruit.
Since the bitterness of grapefruit is largely a function of the furanocoumarins, there is a likelihood that it has been reduced in order to make a less bitter juice.
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CTStan
#190
Its my understanding that you would want to wait for the lowest rapamycin blood level in your rapa dosing cycle before you take a senolytic. This is because you want SASP to be active for the senolytic to work. Rapamycin suppresses SASP.
So if you are looking for a senolytic effect from the “Senolytic Activator” you would take it on the last day before your next dose of sirolimus.
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man_li
#191
Very useful information. Thanks!
I don’t myself have the same view on mechanism.
AIUI Senescent cells issue SASP. I am not aware of any circadian or other variation in the way cells issue SASP.
AIUI Rapamcyin has the effect of making some senescent cells function properly. On that basis they are no longer senescent and don’t issue SASP.
Hence I don’t think there necessarily is a timing issue for a senolytic. Furthermore I think most senolytics are really senomorphics (Particularly those that are HDAC inhibitors - which many are).
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CTStan
#193
I didn’t mean to imply a mechanism. I think of SASP as a marker of 30-70% of senescent cells.
I believe James Kirkland has said that anything that suppresses SASP will attenuate the effectiveness of senolytics.
It is my understanding that rapamycin can suppress some of the pro-apoptotic pathways that senolytics rely on to selectively eliminate senescent cells.
Therefore maximum effectiveness of senolytics would be at the end of the sirolimus cycle.
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man_li
#195
Although this supplement called “senolytics activator” form life-extension company, it’s main compounds are Fisetin/Theaflavin/Quercetin/Apigenin.
I have found Fisetin/Quercetin/Apigenin are all CYP3A4 inhibitors, thus they all have ability to enhance the bioavailability of rapamycin. Theaflavins has on negative nor positive impact on CYP3A4.
So I think I should take this supplement with rapamycin once a week for better bioavailability of rapamycin, despite the supplement’s name is “senolytics activator”.
Right?
1 Like
If you are taking the activator to enhance Rapamycin, you should take it an hour before Rapamycin.
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Justin
#198
A question that seems best placed here.
GFJ or other product that inhibits 3A4 thereby increased absorption, I get that. So, 1mg + let’s say, 6 ounces of fresh GFJ might = 3.3 to even 7 single one mg doses.
So, what happens if you have zero GFJ on the day you took the 1mg. But then, drank GFJ the following day, and the day after that.
Do you change the rate of removal of the drug by the liver?
So let’s say your graph shows that on day 6 you test to less than 0.5ng/ml without any GFJ. If you love GFJ and drink it on day 2, 3, 4, 5 and 6 do you now have much higher blood level? The activity within the gut is not likely to be affected but what about the liver with its 3A4?
Grapefruit juice only affects initial absorption. It won’t do anything hours or days after you ingest Rapamycin.
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Are there any papers that confirm this?
