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.
2 Likes
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?
3 Likes
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.
6 Likes
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.
2 Likes
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.
5 Likes
@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.
2 Likes
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.
5 Likes
@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?
1 Like
No - only. before, or with. I can’t see much value in taking it after dosing rapamycin.
3 Likes
I eat grapefruit 1-4 hours before dosing and take my Rapamycin in the morning or early afternoon.
1 Like
Thanks. I was wondering about that for a while. Funny.
1 Like
It’s been a while since I’ve updated this thread.
I am now alternating between 3 mg Rapamycin+ GFJ and 2 mg Rapamycin+ GFJ every other week.
I am now taking 500 mg Metformin daily as well as 180 mg Bempedoic Acid.
We’ll see how my lipids and HBA1C are when next I test.
7 Likes
Why Metformin and not Acarbose and SLGT2i?
1 Like
I am also still taking acarbose 100 mg before each meal. I just noted the changes I made to my base regimen.
I am not taking an SGLT2 drug yet as I hope the daily Metformin will push my HBA1C levels back into normal zones. If not, I may try one.
I have stopped taking Ezetimibe for now because I want to test the effects on cholesterol by Bempedoic Acid first. After my next blood test, I’ll add it back in and then see what effect it has.
Very good questions! 
6 Likes
I decided I don’t want to mess around with ApoB or LDL and have added Ezetemibe back in. Everything is going smoothly. I will be doing a full body checkup at the end of March with a full blood panel.
My father will be taking Bempedoic Acid + Ezetemibe as well, so we’ll see how his lipid panel is impacted by them. My father had to stop taking Rapamycin due to a bacterial infection in his tooth which simply rages out of control when he takes Rapamycin so he is going to have a root canal before he begins Rapa again.
3 Likes
It’s been a while since I updated this, so here goes:
My father’s experience with Bempedoic Acid + Ezetimibe was a resounding success! His ApoB dropped about 40-50% from a high to a low risk. His inflammation (hs-CRP) also dropped from 1.2 to 0.57. I am now taking Bempedoic Acid + Ezetemibe as well. See below for more info:
I am currently alternating taking weekly 4 mg of Rapamycin + GFJ and 3 mg of Rapamycin + GFJ (14 mg - 10 mg Rapa equivalent). Currently, I am taking an off week as I have a bacterial infection and a mouth sore. Interestingly, the mouth sore caused shooting pain in the nearby molar, but since it has healed, the molar pain has gone away as well.
I have noticed that about every 3 weeks I develop a mouth sore, bacterial infection, or some other injury. I then stop taking Rapa for a week to allow my body to recover. I just finished a 3-day course of Azithromycin and Vitamin C to treat the bacterial infection (and as a mini-DAV experiment). It worked well and I will start taking Rapa again on Saturday.
I am still taking 500 mg of Metformin daily and Acarbose with my carb-heavy meals. I am having my body check at the hospital tomorrow so I should have new bloodwork results available in about 5-6 weeks. I’m really interested in seeing my new HBA1C and lipid panels!
11 Likes
@DeStrider, thank you for sharing your experience.
Are you monitoring your fasting glucose levels with a Continuous Glucose Monitor? I have observed a consistent and systematic effect on fasting glucose levels (100-120 mg/dL) for 6-7 days following the administration of rapamycin (2 mg with grapefruit; 3 mg with grapefruit introduces some sort of glucose volatility on top in my n=1 case). In response to this observation:
- I am introducing 800 mg of Metformin 1-2 days before and after taking rapamycin, as the effects of Metformin on glucose levels become noticeable after 3 days of intake.
- I have decided to cycle rapamycin every three weeks to maintain stable fasting glucose levels for at least two weeks.
Currently, I view this glucose intolerance as part of the therapeutic effects of the starvation-mimicking drug rapamycin. (Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to; Mikhail V. Blagosklonny)
Therefore, I strongly recommend monitoring fasting glucose levels around the time of rapamycin intake to observe personal responses and decide on a regimen.
4 Likes
Thanks so much for sharing all this information.
1 Like
I have just received my blood work results. This was on my protocol plus 500 mg Metformin and 140 mg Bempedoic Acid and 10 mg of Ezetemibe.
LDL cholesterol - 66 mg/dl (Down from 122 mg/dl)
HDL cholesterol - 46 mg/dl (Down from 54 mg/dl)
Total Cholesterol - 123 mg/dl (Down from 194 mg/dl)
Triglycerides - 84.1 mg/dl (Down from 101 mg/dl)
HBA1C - 4.9% (Down from prediabetic 5.7%)
Based on my father’s and my results, Bempedoic Acid and Ezetemibe do what they’re supposed to with a 45-50% decrease in LDL and ApoB.
500 mg of Metformin also moved me out of prediabetes into a normal (optimal) zone.
Since Rapamycin raised both my HBA1C and LDL cholesterol, it seems that these two drugs do a great job of counteracting these bad side effects of Rapamycin.
This also probably explains why Metformin paired with Rapamycin helped mice live longer in the ITP trials. Since mice don’t die of heart attacks, but humans do, I’d wager we need to treat high cholesterol to optimize our lifespan further.
Summary: Rapamycin+Bempedoic Acid+Ezetemibe+Metformin is a winning combination N=2
7 Likes