Improve Bioavailability of Rapamycin (2)

#147

Why do you think fillers and slightly tainted is a possiblity?

#148

ā€œOther statins such as rosuvastatin, pravastatin, or pitavastatin do not interact with grapefruitā€

In case this has not come up.

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#149

Probably because of this information:

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#150

In what form do you give rapa to your dog? Does it have to swallow an enteric coated pill to get absorption as in humans?

#151

Yes - I just give it my regular Zydus or Biocon tablet - I take a small cube of cheese, push a knife into it on one side to make a small slit in it, then slide the tablet into the cheese cube. She gobbles it down without chewing.

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#152

@Joseph_Lavelle @DeStrider I have been thinking about taking Rapamycin a few hours after I take viagra/beet juice or some other NO enhancer, then the question is if the improvement in the circulation of the blood also will improve the amount of tissues/cells that the rapamycin actually reach? Could this be a meaningful option to improve the reach of rapamycin?

I will probably try, but it will be difficult to figure out if the theory works in the real world.

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#153

I wish I could help you with this one, but I am unsure how an NO enhancer will affect the bioavailability of Rapamycin. I think the key to the GFJ and fat (as well as Metformin) is that these either disable the enzyme that breaks down Rapamycin (GFJ + Metformin) or coats and shields the Rapamycin from the enzymes (fat).

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#154

I am not thinking as much on absorption as on the systemic distribution in the body, after the rapamycin is absorbed. Iā€™ll see how it goes.

Maybe increased NO will improve the bloodflow, and then also improve the systemic distribution of the rapamycin. And then more rapamycin will reach more tissues/cells.

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#155

I like it. Better blood flow and lower (but not too low) BP has to be good for the body. As for increasing the benefits of rapamycin, I donā€™t know. Use nitrate test strips (saliva) to find out if your beets are able to help you with NO. Itā€™s an oral microbiome thing.

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#156

@DeStrider FYI, I just did an interview with Daniel Tawfik (and Dr Cohen), Founder of Healthspan. They do not think use of GFJ is smart. It is too unpredictable on top of a speculative drug. Dr Cohen also does not think use of a fatty meal is optimal due to the blunting of the rapa peak. I am rethinking my approach.

Iā€™ll publish this episode in the next week or two.

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Side Effects of Rapamycin (part 2)
#157

I appreciate your concern, but GFJ is the only way I can reasonably get the quantity of Rapamycin I would like. I canā€™t imagine taking 21 pills every two weeks. There will always be some variability, so I have accepted it.

Curious as to why the fatty meal is not recommended? How does it blunt the Rapa peak?

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#158

Fat slows absorption but increases bioavailability. Dr Cohen says the peak is the key. I speculate that the AUC is what gets me in trouble with mTORC 2. I will stop using a fatty meal from now on. Iā€™m still thinking about GFJ as that is a money saver, but I have backed off the dose already.

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Side Effects of Rapamycin (part 2)
#159

What data did he give to support the claim that the peak is the key? Especially for humans, which is the study population we should all care the most about. I ask this because itā€™s directly contradicted by the Mannick study where they dosed a rapalog 3 different ways for elderly patients prior to influenza vaccination. The 20 mg/week dose was no more effective than 5 mg/week, but the higher dose was associated with greater side effects.

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#160

He provided no data. As far as contradicting mannick data: she studied immune system response in elderly people to a vaccine after a short duration rapa usage. Dr Cohen was talking about general healthspan improvement. Is that the same thing? I donā€™t know. Also, the Healthspan company recommends 5-6mg per week, not 20mg. The concern expressed was that using a fatty meal to improve bioavailability was lowering the peak from a normal dose. He didnā€™t say the biggest dose possible was best. I think he was saying too low of a peak isnā€™t ideal. But I tend to agree that a bigger dose, too often, without breaks is not the way to go until more is known.

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#161

Unfortunately, I donā€™t think we really have a ton of data to support this. I suspect its Dr. Cohenā€™s best guess based on the data heā€™s seen. But given the lack of data/studies on this topic, the uncertainty level has to be quite high.

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#162

Agreed. A lot of uncertainty regarding rapamycin.

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#163

Iā€™ve been giving this a lot of thoughtā€¦ GFJ causes CYP3A4 enzyme inhibition, the effect of drinking a single glass of grapefruit juice can last for more than 3 days. So, while it seems great that GFJ gives us a 3.5X boost in peak. I also think itā€™s quite possible that the prolonged CYP3A4 inhibition from the GFJ might cause that peak to be much more prolonged over the next 3+ days rather than the sharp fall we ordinarily expect to see. Thoughts?

The only benefit I see at taking rapa with gfj is to save money. And, as long as I can get rapa from India itā€™s fairly inexpensive anyway. Iā€™m not sure itā€™s worth the unknowns.

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#164

I thought the only effect GFJ had was increase bioavailability, and that canā€™t be a bad thing if you lower the dose.

" I also think itā€™s quite possible that the prolonged CYP3A4 inhibition from the GFJ might cause that peak to be much more prolonged over the next 3+ days rather than the sharp fall we ordinarily expect to see".

Could this be a good thing, as opposed to being bad thing?

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#165

I might not have worded it very well. I was hypothesizing that GFJ might not only increase peak but might also increase half life for the first 3 days because of CYP3A4 inhibition. But, disregard my hypothesis. I just looked it up. It appears that GFJ usually increases bioavailability and peak but not half-life. I say usually because I donā€™t know if this has been studied for rapamycin specifically.

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#166

I think the best answer is I donā€™t know what is best for anyone including myself . Saving money is good but might not be worth the risk (if you perceive a risk as I do). Iā€™m still sorting out my thoughts but so far I think that if I want to continue using GFJ, I should move to a 2 week cycle (or maybe weekly with 3 weeks on and 1 week off) to make sure I get to zero rapamycin. In addition, I donā€™t have any reason to think that flattening (and extending) the rapamycin curve is better even though it might also be a (smaller) money saver. As I tongue my latest mouth ulcer Iā€™m leaning toward a 3/1 weekly cycle.

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