Dr Green new Rapamycin high dose
Dr Green has moved up from 10mg a week to 20mg every 2 weeks. Technically that is the same dose, he just doubles it up and waits twice as long before redosing.
I am shocked that he isnt getting the mouth sores at that kind of dose. I wonder if the older you are and the slower your cell division is that maybe you can tolerate these higher doses without side effects?
Is anyone else experimenting with extreme doses or what is your limit?
Here is the clip discussing it.
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30mg every two weeks for about one year. Experimented with 90mg every 6 weeks (30mg with fresh grapefruit) for about 6 months before, and weekly dose of 15mg prior to that. People that I have placed on a sirolimus regimen generally do fine on either weekly or biweekly dosing. Weekly dose is calculated at .18mg/kg and biweekly is just double that. Bloodwork in all patients has been fine except a bump in total cholesterol. Even on 90mg every 6 weeks I never had side effects. Some patients have a little mood change if they are on a biweekly dose for the first 2 days presumably from alteration in biogenic amines which is probably more pronounced at higher dose. Logic for taking higher dose less frequently is to expose cells to a higher level of mtor inhibition transiently which seems to have been more beneficial in rodent studies using higher levels with longer intervals. Other than reporting on short term adverse effects, I don't think we have any basis on a personal experience level to comment on benefits - maybe after about 10-15 years on sirolimus we will see some differences in "aging". However, it does seem to make some people feel better - again, probably just the biogenic amine effect (more dopamine, norepinephrine, seratonin) in the midbrain.
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MAC. Thanks for correcting my typo and the cite.
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MAC. We do have "a readily available cellular "longevity" lab assay to individually guide in this intervention journey". You must not have read my comment above. I proposed using it to dial in the dose for on a personal basis to give it a custom fit.
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MAC. I believe Dr. Green's current weight is about 150 lbs which makes his biweekly dose about .15 mg/kg/wk which is not much different than my preferred dose of .18mg/kg/wk. My dose is based on rodent --> human dosing conversion using 42ppm rapamycin chow daily feeding and taking into account (adusting) for even higher dose paradigms (2-3X that) and extended dosing intervals in rodent studies which seemed to decrease dyslipidemia and hyperglycemia and even improved health/lifespan. I did this work long ago and don't remember the details exactly.
I appreciate the effort to figure out optimal human dosing looking at laboratory data from ourselves but I don't believe it is possible. The rodents had far greater levels of laboratory deviation yet had extended health and lifespans which seemed to be greatest when given massive doses for a 3 month interval and then stopping. Realize that 3 months to a mouse is 10 yrs to humans.
At this point I'm fairly comfortable dosing at this level and I believe we cannot know if we are having an effect on aging until a long time has passed. The proxies for life and healthspan (laboratory values or DNA age) are interesting but do not prove anything. At least these proxy measures are not going in the wrong direction which provides some solace.
Of note, I did not continue 90mg every 6 weeks for two main reasons. Relying on grapefruit juice to drive absorption creates uncertainty as to the exact amount my body was absorbing due to variability of GFC affect (2.5-3.5 times). The second reason was that I noticed some swings in mood and motivation which are neurotransmitter related effects. Typically these trend positive with sirolimus but too much of a good thing can produce opposite effects.
I cannot recommend any particular dosing of sirolimus for health and lifespan extension to people who are not under my care for obvious reasons. I have my own dosing models and some observations in a limited number of people over 3 years or so along with 35 years as a practicing physician which may have some value. Sorry I can't provide better info. I try to limit comment on this topic to every couple years or so because I think it takes alot of time to observe any "anti-aging" benefit or potential problems. So far -- it seems good.
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Fred Cloud you mean phenoage? That’s been proven to be 100% correlatable to human longevity/all cause mortality? Cite the studies.
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MAC. I am not here to fetch studies or prove anything to you. You seem rigid and obnoxious and I regret helping you.
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Mark Thimineur Dr. Mark. As a follow-up, have you continued regularly applying your rapa cream treatments per your original post? If so, how' s that working out?
Thanks
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Michael Twice daily. Increased concentration to 6mg in 4 ounces DMSO/Aloe cream. The effects on face: I have not developed any fine wrinkles or furrowing - skin completely smooth - no crows feet, smile lines, or forehead lines. My spouse is 10 years younger and had some fine wrinkles before starting which have been gradually decreased - her skin is smoother and healthier looking. I think I have been applying for about 30 months. I made the mistake of giving it out to some friends who hound me for it when they run out. Some people just don't want to make it themselves.
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Van talked to some individual who are experimenting with it internasal. They said you feel it instantly at a dose of 130ug. Takes away all brain fog immediately. You could do this in addition to your regular ROA. Want to try it?
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Van What about GFJ commercially purchased- like Tropicana ….
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Al m Tropicana, no go. Processing take necessary chemical out. ONLY fresh grapefruit will do. I weigh 400 grams of pulp and juice and split it from night before and 1/2 hour in morning before taking rapa. Grapefruit juice has a chemical that will block our bodies from diluting the bio-availability of rapa. Cancer patients have been using it for years.
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Van would be too much sugar for me in the evening (200g grapefruit has about 12-15g sugar). evening spikes don't seem to play well with my sleep quality (partly supported hypothesis).
You can take it all in the morning but need to wait until lunchtime for taking rapa. That's how long it takes to decrease CYP3A4 levels (implied in the Cohen et al. 2012 paper).
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Van How can you tell if processing removes that chemical?
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Chris Los I'm glad you mentioned that. Since I take an evening statin, I cant take Grapefruit in the evening.
My doc says occasional grapefruit in the morning would be okay. I gather there is a lot of variability between individuals and between grapefruits, so this is rough estimating. I have to balance out the gfj desired effect on sirolimus and its undesired effect on my statin in late evening. I think I can get that balance by taking gfj first thing in the morning and waiting 3 - 4 hours before taking sirolimus. Similar to your schedule.
Since I prefer ruby grapefruit and because I'm not getting full effect of the timing of the grapefruit, my guess is I will get about a 2 fold effective increase in sirolimus.
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chuck stanley You may be interested in knowing that statins are also mTOR inhibitors. You can verify this quickly with a Google search. It is why some individuals get a muscle aches from statins.
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Peter H. Howe Interesting. There might be an association with my exercise related nocturnal leg cramps. Although I take minimal dose statin, plus I do take CoQ10, it might be worth discussing a statin vacation.
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chuck stanley Chuck if you are like me you "HAVE TO" have a statin please be careful.... . I had a bypass ~30 years ago and there is nothing I can do, including veganism, to control my cholesterol at an acceptable level. High dose fish oil reduces my need for high dose statins by lowering triglycerides and thus my LDL-P and particle size but it is not enough. My problem is genetics as cardiac arrest is pervasive in several sides of my family.
Note statins also reduce your androgens and estrogens so you should monitor these. I supplement with hormone replacement therapy including pregnenolone, DHEA and testosterone and monitor through Life Extension and Lab Corp. On the plus side statins activate the Klotho gene. Google will readily verify these statements.
Be careful and monitor.
Good luck.
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Mark Thimineur are you aware of any comparisons between the cream you make and commercially available Tacrolimus cream?
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Mark Thimineur would you mind sharing the % DMSO in the cream you use? I see a 4 oz cream with 70% DMSO/30% aloe in a cream base available online, for instance. Thanks!
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Sorry never mind, I searched the forum and found where you posted rapa cream recipe previously.
Since I'm hesitant to apply DMSO to my skin and I want the rapa to stay *in* my skin rather than be absorbed through it, I did the following:
6mg rapa dissolved in 25ml of 95% ethyl alcohol (Everclear) then gently mixed into 4oz of CeraVe lotion. Seems to have worked beautifully. I guess we'll see if this particular formulation actually does anything....
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Mark Thimineur Any recommendation on an expiration date of the home made rapa cream? I have some from 2019. Still good to use? Thank you
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Michael
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Paula Marie How does one correctly make the cream?
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Paula Marie It's Mark Thimineur's formula, found here:
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Mark Thimineur The innate system you touch upon is my big issue. Have their lymphocyte counts been tested?
Resuming rapamycin after two months to let my lymphocytes recover, a mere 3 mg of rapa [1 mg + two grapefruit fruits) caused my lymphocyte count to drop by over 35 %, to less than half of the low mark of the normal range.
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The biweekly dose is 30mg sirolimus without grapefruit juice. Every 6 week dosing of 90mg was 30mg sirolimus dosed with grapefruit juice. There are GI side effects dosing over 40-50mg at once so grapefruit juice is required to avoid these side effects when taking more than that amount. Bloodwork plugged into the Levine calculator and also DNA sample analyzed via Horvath clock indicate biological age at 77% of chronological. Probably mostly ancestral genetics as most family members that I have known lived to late 90's or 100+ years with minimal age related disease. Dose response for anti-aging would require a well contructed study with enough subjects to meet statistical power requirements. I think the dog aging project may be of interest once they release data which may provide some data to help guide future study in people.
