I couldn’t handle Rosuvastatin 5 mg every other day so I’ve given up statins completely.
I am considering Ezetimibe. I have the prescription but I am worried it will affect my muscles like the statin. Have to try it to find out though.
I won’t be buying a 6 month supply up front this time.
What a shame. From my experience with Ezetimibe I would hope that you’d be unlikely to have any adverse effects. I certainly haven’t noticed any.
I finished listening to the podcast, which is great as it summarizes everything we know and don’t know about rapamycin.
But from my understanding of potential optimal dosing there is a possibility that the key would be to extend AUC (time in which rapamycin is effecting mTOR, especially MTORC1) and doing it transiently to minimize effects on MTORC2.
Since MK said that dogs are probably under dosed with 0,15 mg/kg and they metabolize rapamycin quicker then humans I was also thinking that another dosing regime might be better than once weekly 5-6 mg.
Going with a high dose once weekly or fortnight might be one way of extending AUC another is what Pankaj Kapahi is doing (1mg/day 14 days and 14 days off). Since some tissues might need higher dose of rapamycin I was thinking would maybe something like a three day pulse treatment be better? Maybe 12mg day one, 8mg day two, 4 mg day three followed by a washout period?
I had severe muscle issues with all the statin types and no problem at all with Ezetimibe (even when eating a grapefruit!!).
Lipid levels came down.
Have since added in Pantethine and lipid levels have fallen further (and still no muscle issues).
I suggest you take the plunge and start straight away.
I have added pantethine to my stack.
I agree, think it is reasonable to take more than two weeks off, after a few 20 mg doses. Personally I am thinking about a longer flush out period than 3 weeks.For me I am considering something lika 6 weeks off rapa…
I am curious why do you think you would need longer washout period? Wouldn’t be more rational since you need mTOR (MTORC1 to be more precise) inhibition for autophagy where most of benefits of rapamycin probably lies and with such a large dose and a long washout you are really stimulating autophagy for relatively short periods, while it probably needs to be in effect for as long as possible to be effective. Large dose is in my view just a small increase in length of mTOR inhibition and is used more to increase the chance for rapamycin to reach as many tissues as possible.
I think a few longer washout periods each year, might reduce the risk of side effects building up. And I like to have a few periods of anabolism each year. But if there is data or scientifically based reasoning that suggests that this is counterproductive, then I will change my approach.
What do you think could build up?
But if you take really long washout periods wouldn’t make it more sense to do periodical fasting or fasting mimicking (Longo approach) few times a year instead of rapamycin? Just a thought, since it is similar in stimulating autophagy. But also another thought, even taking rapamycin is not really completely stopping catabolic state, it is just slowing it down probably.
@DeStrider Are you expecting to get a higher dose equivalent absorption (3-7x) AND a longer half-life from using GFJ? Has anyone done the half-life curve study using GFJ? Also, what is the effect of continuing to take GFJ after dosing, say every 4 hours? Does the rapa load stay high longer?
On my father’s side, I have a family history of cardiovascular disease and early death. I have made it a priority to reduce the risk of cardiovascular disease. My DNA analysis shows an increased risk for type 2 diabetes. I am on guard to reduce the negative impacts of rapamycin on lipids and glucose metabolism. I have read, on this forum, members have said that they experienced changes in lipid and glucose metabolism. changes, which they attributed to high doses of rapamycin, and that it took some time to reverse those changes. That is why I plan to take some time off after taking high doses of rapamycin.
Grapefruit juice only helps with the absorption which reduces the enzyme that breaks Rapamycin down before your body absorbs it. Based on the studies, grapefruit juice should increase the absorption by 3-3.5X. This is also why compounded Rapamycin is ineffective. The Rapamycin isn’t protected by the enteric coating that protects against the enzyme and all of the Rapamycin is effectively destroyed before you can absorb it.
GFJ shouldn’t affect the half-life other than by increasing the initial amount of Rapamycin in the bloodstream.
Taking grapefruit juice after dosing should have no effect on Rapamycin absorption or levels. It simply enables your body to absorb more on initial dosing.
When you take a large dose you have to be wary of inhibiting MTORC2. If you take a large dose 20+ mg, it takes at least 2 weeks for the Rapamycin to clear and your MTORC2 to begin forming again.
That’s why when I take a large dose, I need at least 2 weeks to clear the Rapa.
Second day after large dose, I feel great. Got 12 hours of sleep (I was fatigued). My ankle is great. My aches and pains are gone and I feel energised. I hope it stays this way.
@DeStrider Maybe I missed it, what time of day do you take your Rapa? I’ve been taking it in the morning, but thinking evening would be better so that I am fasting after taking it.
I’ve taken rapamycin in the evening only once, and didn’t get to sleep until 4am or 5am, and I hear thats not an infrequent situation. Your mileage may vary.
@RapAdmin I faintly recall reading that you used to take grapefruit AFTER your rapa dose. If true, was your thinking that would extend the AUC?
No - only. before, or with. I can’t see much value in taking it after dosing rapamycin.
I eat grapefruit 1-4 hours before dosing and take my Rapamycin in the morning or early afternoon.
Thanks. I was wondering about that for a while. Funny.