I just got my first Rapamycin prescription filled. I got a local functional medicine doctor to write it and send it in to Walgreens. I got Dr. Reddy’s Sirimulous 1mg. tablets and my insurance paid for it at the generic copay of $7 a month. My doctor doesn’t write many prescriptions for it so she won’t want her name out. I have Hypertrophic Cardiomyopathy so I hope that the Rapamycin will at least stop my heart muscle from overgrowing and adding more scar tissue.
Almost every week I fast on Tuesdays for about 40 hours. I do a long sauna/hyperthermia thing on Friday night and Hyperbaric Oxygen on Mondays. I would like hear anyone’s suggestion on which day I should pick to take my weekly dose of 5 mg. Should I take it Monday night with my last meal so it is fresh in my system when I fast to help with the autophagy? Should I take it with my first meal on Wednesday to turn down the MToR on the days I am eating? Should I take it every 8 days so it lands on a different day each week? Is it better with a meal or on an empty stomach?
Personally I would combine HBOT, fasting and Rapamycin. I would take Rapamycin perhaps 10 hours into the fast so that the peak effects of Rapamycin combine with the peak effects of the fast. At a minimum I would take it at the start of the fast.
HBOT is about stimulating the transcription factor HIF-1α which also has the ability to stimulate autophagy
The short answer is nobody knows… so whatever you do, treat it as an experiment and adjust to how your body responds.
One of the issues is that one of the ways in which rapamycin is thought to work is via autophagy. As you probably know “Fasting” is also a good mechanism for encouraging autophagy. The issue of course is that we have no way to measure autophagy in humans (clinically) yet, and we also don’t know what the optimal levels of autophagy are, nor do we know the dose/ response relationship in terms of all the possible autophagy activators.
So, given the lack of information we have I would test different strategies that you’ve asked about and see what works for you (in terms of how you feel). Its going to be a long time before we understand these things from a clinical standpoint with evidence-based medicine and data.
@RapAdmin is right “nobody knows”. My personal view is to try to maximise the pressure for autophagy at any one time. However, that may not be sensible. What I would say also is to build up to things if you can.
Do you know what the maximum partial pressure of Oxygen that you are breathing is?
The question that matters, however, is the partial pressure of Oxygen. That depends on what air you are breathing. Are you breathing normal atmospheric air which is 21% Oxygen. That means the partial pressure of Oxygen would be 0.576 atmospheres. (58.3632 kPa, 8.465 psi, 437.75994 mmHg)
What is the Oxygen mask attached to? Is it a bottle of Oxygen or an Oxygen concentrator?
As an interesting question
a) How long are you in the chamber for, and for how long of that do you wear the mask.
b) Do your fingers start tingling whilst in the chamber
c) Do your fingers start tingling when you leave the chamber.
What is interesting about HBOT is that it is in fact the reduction in Oxygen levels that stimulates protein production changes in cells via the transcription factor Hypoxia inducible factor-1α.
What is unclear is for how long the higher partial pressure is needed before removing the higher partial pressure causes the effect.
I studied a number of papers about this and did a summary which I posted here:
I think you’re doing the right thing, though I’m not an expert. I was fasting with the rapa dose, now I start the fast noon the day before. I take rapa the next morning , then continue fasting until maybe 6PM.
My idea was that fasting increases MTOR2, but it’s possible (only in my mind) that this may not happen if you are on Rapa. So the fast should be toward the end (nadir) of the dose. Good Luck,
I fast when I take mine, if nothing else to avoid big glucose spikes, since if I recall correctly, rapamycin can transiently induce insulin resistance.
I disagree with what many above have said. I think it’s generally best to take rapamycin on days you don’t fast. Such as perhaps on the day after you end the fast, to prolong the mTOR inhibitory period.
I understand people wanting to take rapamycin during fasting to try to maximize autophagy activation but I think chances are good that’s largly a waste, since evidence indicates that rapamycin only reduces mTOR when it’s elevated, but not when it’s already low as it would be when fasting.
I haven’t seen any study that shows that rapamycin reduces mTOR or increases autophagy during fasting so I think it’s wishful thinking to think it does that to a considerable extent. Also the animal longevity studies gave rapamycin with food, so that’s how it’s proven to be effective.
Another thing just occurred to me that I didn’t mention. Taking rapamycin while fasting is like trying to drive mTOR lower when it’s already very low. This could possibly increase the chances of an mTOR rebound. I would avoid extremes here.
@Olafurpall What is your approach to re-establishing the anabolic / catabolic (growth / autophagy) cycle? If a person is using a weekly rapa cycle combined with fasting or low protein (or other mTOR inhibitors such as circumin, metformin, etc), how many days of mTOR “down” vs mTOR “up” (resistance training, leucine, lots of calories, enough EAA) do you think makes sense?
It is an interesting thought. I am taking Rapamycin tomorrow and I intend fasting tomorrow. I am also maximising other AMPK initiators.
I think there is an interesting rebound from increasing ATP and AMPK at the same time which is that when you stop doing this (and I am a fan of cycling things so I do this for a number of days then stop) it appears that blood pressure drops lowish (waking this morning was 114/58-65 a slightly high heart rate because of acetate vasodilation).
However, I also take Rapamyin relatively infrequently (I am currently taking it every 21 days, but I may take it more infrequently as I don’t actually like inhibiting mTOR on a semi permanent basis.).
You may be right that any rebound effect from reducing mTOR is increased by doing other things at the same time. However, I do wish to maximise mitophagy as a proportion of the mitochondria in the cell (whilst staying at reasonable levels).
I did one of the trudiagnostic tests whilst in the middle of one of these sequences and hopefully will get my result by the end of this month. I only have two data points, but considering citrate in isolation my DunedinPace was lower (0.78) for the higher citrate (the other was 0.82).
That’s hard to say. None of us really know, but I think a big clue is that calorie restriction works well in animals and that’s probably like a constantly low mTOR with daily spikes that are more moderate from the reduced calorie intake. So I don’t think people necessarily need mTOR up days unless they are eating low calories and are at risk of sarcopenia. Note that there are people that have tried doing alternate day fasting and have maintained a healthy body weight that way. Other people, like me, would get very skinny if they did that. So while some people would be good with 3-4 low mTOR days and 3-4 high mTOR days, others clearly need more if they want to maintain a certain body weight. My opinion is to do as many low mTOR days weekly as you can with your ideal body weight and muscle mass in mind. This is considering that most people don’t want to do calorie restriction and be very skinny.
That’s interesting. I doubt that a lowering from 0.82-0.78 is significant though. I am not sure what the variability between tests is but I know these epigenetic tests are generally not so accurate so I would guess you need at least a 10% change to be fairly certain it’s a real change, or alternatively a smaller trend from the average of several measurements.
I agree. When I looked into epigenetic tests briefly earlier this year, I concluded that the DunedinPace is the best one. However I’m still not sure how much of a change you need to see between measurements to be confident it’s an actual change. They should show how much of a variation there is if a person measures his DunedinPace every day for a week or several times within the same day. All these tests are kind of useless without error bars for the measurements. Optimally they should provide that info.
It is an interesting nugget of information. With blood tests I have a better idea of how reliable they are, but I get one of those pretty well every week.
I don’t think you can be confident in blood tests telling you how reliable they are, although they can help you get some idea I guess. We don’t know how quickly positive and negative changes in health and aging rate are reflected in the DunedinPace score. We also don’t know how various blood test parameters specifically influence that score.