John - interesting. Have you done any blood testing to know how well the sublingual rapamycin is being taken up?
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J0hn
#229
I havenāt done any blood testing for drug levels. Unfortunately I live in the UK and my nearest testing centre would be London, and Iām going through what will probably prove to be a messy divorce.
Iāve done everything I can to enhance lingual vein absorption of drug. Iāve reduced the dosing volume down to 120ul of transcutol based dosing solution by extracting the rapamycin from the tablet.
Iāve also maximised contact time with the vein by applying a 10ul droplet to each lingual vein every 30 seconds, with my head back and tip of tongue touching the roof of my mouth.
I have in the past also added 5ul of a food colouring dye to the dosing solution and there doesnāt appear to be any pooling at the base of the tongue.
I love to know what my drug levels are using this dosing technique. I have tried to buy an ultra sensitive Rapamycin ELISA kit but unfortunately the company wonāt sell to a private individual.
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Meta Analysis of Rapamycin enhancing strategies.
States multiples for Ketaconazole, GFJ and half life of Rapamycin.
This answers lots of questions about Rapamycin.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410974/
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A lot of reading. So the peak is around 2.2 hours. I can definitely feel the effects after 2 hours. One thing on the positive side my nose that usually suffers from allergies no longer seems to get that any more.
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What I meant is if you increase your pills without GFJā¦ see if the effects return. If it returns then it is just normal. I personally do not like to consume more āmedicationā than necessaryā¦ I rather use other means to boost the strength.
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SNK
#233
That sounds like quite the chore to do all that. Have you ever tried to just put the pill under your tongue and let it dissolve. I assume it will dissolve slower because of the coating but by the looks of it, it should disolve? .
@DeStrider This is very helpful. Thank you.
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brand
#235
assuming 1 grapefruit is 6x
would 1/2 grapefruit be a 3x multiplier.
e.g. 1mg with half grapefruit=approximately 3mg
What is a good way to mimic a 3mg dose.
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I have seen in no studies on how the fruit impacts bioavailability, so I would not assume anything, or even venture a guess. In the past Iāve used 1 grapefruit two hours prior to taking the rapamycin and Iāve assumed its approximately equal to one 8 ounce glass of GFJ, but I donāt have any data to support that assumption. Perhaps if you squeeze a grapefruit and see how much juice you can get from it you have slightly better information.
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I have never seen a grapefruit giving 6X. The standard assumption is 3X at maximum inhibition of CPY enzymes. If you donāt take enough GFJ, you can assume less than a 3X multiple.
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SNK
#238
No, your assumptions canāt possibly be right. Once you get enough grapefruit to suppress that enzyme (donāt know the name, and too lazy to search its name) then you could eat 15 grapefruits if you like, and the effect would still be the same. Letās say the enzyme is blocked with 1/2 a grapefruit and that would give you 3X (this I think can vary from person to person and other variables) then even five grapefruits would still give you 3X.
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brand
#239
It would be interesting to have some kind of protocol to take 1mg Rapamune only while mimicking 2,3,4,5 and 6mg via other means (not necessarily GF only).
Maybe by monitoring side effects to gage strength?
e.g. would 2mg taken with a meal or fat increase by 30% therefore making it similar to 3mg.
How could this be achieved while only taking 1mg.
Itās most likely too difficult to accurately determine as different people respond differently to both Rapa and Rapa/GFJ combination.
I posted before. 5mg with GFJ on an empty stomach, no olive oil is tolerable.
6mg with GFJ produces diarrhea the next day. I have repeated this experiment enough times that I know the max dose for me is 5mg with GFJ,
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No, it doesnāt work like that. First of all, you canāt assume that one grapefruit will give you 6x. Even if it did, that doesnāt mean half a grapefruit would give you a 3x multiplier. Half could give you a lot less or even nothing at all.
You take 3 mg and measure your blood levels 48 hours later. Then you take 3 mg with grapefruit juice and measure your blood levels 48 hours later. This will give you a multiplier that you can then use to estimate how much you need to take with grapefruit juice to get as much as you get from 3 mg without grapefruit juice.
If you canāt take blood tests there is no way you can know how to get the equivalent of a 3 mg dose for you. You could make educated guesses, but they can be way off.
I have seen more than that although Iām not talking about rapamycin specifically. Iāve seen the same dose of grapefruit juice give everything from 0x to over 8x for a particular drug within the same study and testing conditions.
Thatās true. The problem is, what constitutes enough GFJ will be highly individual. Some people might get a lot of inhibition with 100 ml while others might need several times more. I saw some studies that showed that 200 ml was a minimum dose with lower doses generally not causing any effects in many people. My guess is therefore that lots of people here that take only about 200 ml or less might be getting little to no effects from it. It would be safer to take 300-400 ml if one wants to be more certain of getting increased bioavailability. But even then youāre going to need blood tests to be sure.
My advice for those that plan to take rapamycin with GFJ regularly over the long run for longevity is to find a way to get blood tests even if you have to travel somewhere to do it. You donāt want to take 2 mg rapamycin with GFJ for a decade, thinking youāre getting the equivalent of 6 mg, only to realize later that youāve only been getting the equivalent of 2-3 mg.
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Thor1
#242
So are you saying that we donāt actually have evidence about GFJ (when, how much to drink, the actually increase in bioavailability etc.) but we do have evidence on the efficacy of taking rapa with a high fat meal? This seems like a no brainer so Iām double checking.
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We have evidence for both GFJ (which varies in effectiveness but is usually around 3X) and high fat meal (which is around 0.5X). If you do both, it ends up to be about a 3.5X multiplier give or take based on your biology. This is why some people do the blood tests. Others play it by ear (by monitoring side effects).
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@Thor1 A search on the forum threads will reveal a lot of studies and opinions about saving money on rapa by way of fatty meal and gfj. There is no other benefit I am aware of.
Here is whatās in my head:
Adding fat will lower the blood peak of rapa by slowing the absorption but will increase the ābioavailabilityā (measured by AUC?) by ~30%. Does slower absorption matter? I donāt know.
The timing of the gfj matters. 2-3 hours before Rapa dose gives the biggest benefit but up to 12 hours before can have an effect. GFJ with the rapa might not have time to do its job well.
The amount of gfj matters. A single grapefruit has 120-240ml of juice. One might not be enough for you. Aim for 300-400ml, per @Olafurpall
Some people here buy GF juice. Some people squeeze GF. I eat the grapefruit because I like GF. Doing a concurrent fast (okay maybe not a real fast due to GFJ) while eating GF is very easy as GF is an hunger killer for me.
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Thor1
#245
And you donāt care about the impact of a high fat meal? Again, idk what is enough fat to be a high fat meal. Iāve read a teaspoon of olive oil but idk if that is enough.
I do care about the impact of a high fat meal, I just donāt talk about it much because itās not nearly as important as the impact of GFJ. The reason for that is because getting adequate fat with rapamycin will in most people have a much smaller effect than GFJ, and more importantly, the effect will be far more predictable than the effect of GFJ, meaning it will not differ a lot between one person and the next so you donāt really need blood tests to see how you respond to extra fat with it.
Regarding what is enough fat to maximize bioavailability of rapamycin, I think a teaspoon of oil would generally be enough. You donāt actually need a lot of fat to enhance the absorption of fat soluble compounds, you just need enough so that the fat soluble compound can be mixed with the fat and absorbed along with it. Note that fat soluble supplements such as vitamin E, lycopene, astaxanthin, lutein and CoQ10 come in gel caps with just a small amount of oil, usually less than 1 ml of fat. Thatās generally enough for good absorption. The same would likely be true for rapamycin. A possible exception to this would be if youāre taking it with a meal that contains some chemicals that bind fat and prevents its absorption, like a meal containing lots of soluble fiber. If you take rapamycin (or any other fat soluble supplement/drug) with such a meal itās probably better to get even more fat with the meal, like a tablespoon or more.
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Karel1
#247
The question I would like to pose: rapa is probably very soluble in dmso. Possibly a full dose can be dissolved in just 0,1 or 0,2 ml dmso and after application to the skin reach circulation for a very high percentage bypassing poor adsorbtion in the gut and first pass metabolism in the liver.
Though dmso is a very potent substance in its own right local side effects may be minor and the garlic odor may be acceptable.
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