Rapamycin self-experimentation
I've just begun a 10 week self-experimentation with RapaPro rapamycin. I'll be taking 5 mg once a week, which is roughly the dose that Dr. Alan Green recommends on the high side and seems to be about what Dr. Attia supports/recommends.
I'm a 48-year-old male in generally excellent health. I've been following longevity science for a decade now and in the last couple of years have gotten more serious about it and also in trying new things that seem to have good data to back them up. I've been taking NR for a couple of years, as well as resveratrol and phosphatidyl choline.
After my first dose a couple of days ago I had some mild body euphoria that seemed to result from reduced inflammation. I felt less creaky overall and hummed with pleasure. I'm not measuring any biomarkers quantitatively, but will report my results in terms of reduced cold symptoms (I've had a mild sniffle for months now due, I think, to an ongoing tooth infection and the fact that I work out pretty hard a few times a week, leaving less bodily resources to kick my sniffles), increased/decreased energy, feeling of wellbeing, etc.
Dr. Green convinced me that there is real potential here when he talks about going from feeling very old at 70, unable to even walk his dog without suffering, to biking 40 miles and feeling great after.
I'd be curious to hear others' experience with rapamycin or comments on my dosing and schedule.
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This blog is a little long – sorry. Almost all self experimenters are motivated and generally in good health. Benefits of low dose intermittent rapamycin may not be obvious. I have some insights which may be food for thought. I have practiced interventional pain management for nearly 30 years and an early adopter of rapamycin and metformin for personal age reversal – doing great. I have prescribed rapamycin to about 50 chronic pain patients representing the exact opposite of a typical self experimenter in terms of health. Instead, these very damaged human beings have severe diseases and injuries, often on opioid analgesics, many having implantable devices, and generally doing poorly. They cannot exercise and are far from optimal health or weight.
My observations suggest a variety of interesting rapamycin affects on these human beings. Pain reductions are quite notable for peripheral neuropathy, migraine headaches and other craniofacial pain (i.e. post traumatic headaches, trigeminal neuralgia, post craniotomy pain).
Psychiatric effects seem consistent and potent. At least 1/3 of this cohort experiences anti depression, anti anxiety, increased motivation and mild euphoria. These effects appear durable and lasting.
Certain diseases and conditions are notable for improvements in the underlying issues. Rheumatoid arthritis and inflammatory bowel disease seem to improve even prompting other specialists to remove disease modifying agents such as tumor necrosis factor agents etc. Multiple sclerosis seem to improve in terms of pain and neurologic symptoms. Traumatic brain injured have experienced cognitive and affective improvements.
Almost all these people are 55 and older. One much younger professional with lifelong affliction of severe anxiety and ADHD (both requiring treatment) had a remarkable improvement in these disorders unrelated to the pain condition and consistent with psychiatric effects mentioned above and no longer requiring ADHD or anxiety treatment by taking only rapamycin .05mg/kg/week.
Effects are also dose dependent. Purposely cycling patients between the higher dose levels of around 0.1mg/kg/week to the lower levels of 0.05mg/kg/week show better pain reduction and other described effects at the higher dose. Cycling is done to help understand the effects better and because I’m a believer that too much of a good thing may be bad. Patients are cycled for 3 straight weeks on higher level then 3 weeks on lower. I do the same for myself.
It appears that judicious use of mtor inhibitors such as rapamycin could be used as adjunctive therapy for a variety of diseases. It is a shame that such is not likely to be the case for many years. I think that people who are otherwise healthy and motivated are likely getting significant benefit from rapamycin. It's just not as obvious.
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uzoma iwuagwu It's in the METHODS section:
"At 3 months of age, mice were divided in two groups, one of them continued with control chow and the other were changed to chow-containing encapsulated rapamycin at 42 ppm (mg of drug per kg of food). Food and water were provided ad libitum and measurements"
Clearly, chronic rapamycin intake vs intermittent. Cannot tease out absolute rapamycin intake without knowing daily food intake. Anyone know what a mouse eats ad libitum?! So there's a dose/frequency disconnect to typical anti-aging human rapa usage.
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Henry walker Blagosklonny commented on this on Twitter. Basic is that mammals need mTor for growth early in life. Rapamycin limits this so would shorten life if given too early. He thinks this supports his hyperfunction theory of aging.
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MAC There is now a singular exception to the longevity effect of rapamycin in all life forms, some of which were bred specifically to represent a condition or disease seen in humans. This one exception is short telomere disease. In humans, this is a rare inherited chromosomal mutation manifesting early in life with organ disease and failure. There are no disease modifying agents and only drugs to manage the organ damage. So, this is one rare condition in which rapamycin needs to be avoided. BTW, these people don't live long and they are sick (and rare).
On a more general or macro view, humans in the "wild" are not like lab experiments with specially bred rodents living in perfect enviroments fed the correct foods etc. Individual variability in the genome, environment, behaviors, injury, etc are massive in the human population. It is amazing how individual we all are. Although mtor can be inhibited in us all, there is little doubt that the overall benefits or detriments will vary by individual.
Unless a person has the rare short telomere mutation (and suffers the severe organ damage at a young age), there should be little concern in regards to mtor inhibition in the case of "normal" aging. Perhaps we all exist along a normal distribution curve with most of us having average telomere length, and a few of us shorter and a few longer telomeres. In this normal distribution we don't have the "disease" of short telomere represented in the rodent study. Perhaps those with the slightly shorter telomeres benefit somewhat less and the longer somewhat more. We won't know this for a long time, if ever.
I've used the gambling metophor before. Using intermittant rapamycin for longevity is playing a pretty good hand with what we know. This study on telomere deficient rodents does not appear to change that, at least in my humble opinion.
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Paul Beauchemin One item that stands out to me is the small N of only 14 mice in the -/- group that shows only a small difference between the control and the rapamycin fed mice.
I cannot explain their results. My only guess is feeding rapamycin when the-/- mice are too young. But they die young. So how to redesign this experiment?
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Very enlightening clinical observations. Resolution of such a diverse spectrum of symptoms would seem to me to define anti-aging. But then, in healthy individuals how would one judge the impact? Some interventions (other than rapamycin) show little to no effect on healthy individuals.
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It was suggested I order rapamune from YCDS...anyone have experience with them?
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My first set of blood tests since starting Rapamycin in late November / early December. Additionally, I completed one Dasatanib/Quecertin 3 day protocol in January. My diet has changed from primarily plant-based to low-carb ketogenic which may explain some of the cholesterol changes.
Do y’all see anything I should be concerned with?
It looks like my insulin sensitivity has dramatically improved on the positive side. On the cholesterol side my triglycerides are significantly better offset by the increase in LDL-C.
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Sam Biller Predictable drug effects: minor dyslipidemia, borderline Hct. I see nothing to be concerned with - these minor blips are common among the patients on longevity rapa dosing. The macroscopic view is that prevention of all age related disease in every organ system and prevention of malignancy dwarfs these minor lab deviations. Small dose of a statin corrects the dyslipidemia and the HCT may be self correcting but it is nothing to worry about at this time. I would suggest waiting 6 months to check again unless you just want more data to trend.
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Mark Thimineur Thank you for the quick response! I’m visiting my primary care physician the week after next to discuss. I’m not too concerned and will likely follow-up with additional testing later this year as you suggest.
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Sam Biller looks like all the biomarkers going in the right direction per the Levine spreadsheet
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Sam Biller looks like you have a 15 year predicted improvement in DNAm Age from the spreadsheet posted on this website! I started rapa Dec 1 and also did a dasatanib/quercetin one time treatment. Also take metformin. What else are you doing to achieve this? diet/fasting/exercise other supplements/drugs?
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Paul Beauchemin Hi Paul, thanks for the feedback. I didn’t even know about the Levine spreadsheet. Very interesting. I downloaded the spreadsheet and ran the age factors at the linked web site as well. It looks like my predicted age is in the mid 30’s.
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Sam Biller regarding protocol... I’m a patient of Dr. Green.
Meds:
Rapamycin 6mg weeklyCandasartan 26mg daily
Tadalafil 5mg daily
melatonin 3mg nightly
D&Q - 1 treatment
Current diet:
Ketogenic with lower fat to accelerate weight loss. I’m currently 6’1”, 170 lbs. Lean body mass is around 135 lbs. I want to get my fat down another 10 lbs.
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Sam Biller Why do you suppose that the BUN deteriorated over 3 years? The Creatinine improved slightly so we should not blame the kidneys. Perhaps you were a little dehydrated when you took the test? It is well known that there is an increase in cholesterol and your tests seem to confirm this. Despite a very impressive HDL result would you consider a statin? Your diet probably added to the the mild anemia so obviously a minimal change should improve the results. Otherwise, very impressive.
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Jonathan Horwitz Hi Jonathon, I think the change in BUN is almost completely attributable to my change of diet — I went from a primarily plant-based diet for 3.5 years to a ketogenic diet (low carb, moderate fat, protein at 0.8-1.0g per pound of lean body mass). I seem to recall that a plant-based diet has a dramatic impact on BUN but would need to look up the source. The change was precipitated by my desire to lose some body fat. I was putting some weight back on with the plant-based diet. In hindsight, I think the weight gain was mostly attributable to fats sneaking into my plant-based diet. I find it a lot easier to maintain the low carb diet versus the low fat diet although the impact on longevity is not clear.
Regarding a statin, prior to going plant-based, I was taking a small dose of Crestor but stopped due to definite muscle pain. I don’t plan on going on a statin anytime soon. Since I’m losing some weight right now, my physician and I have discussed retesting in 6 months with some more sensitive lipid testing to determine particle counts, etc.
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Sam Biller I take 1.25mg daily crestor. my gf takes 5mg. we supplement CoQ10. No muscle pain. What dose were you taking?
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Sam Biller Here is a video, I would encourage everyone to watch. It is done by Edward Omron, MD. He has also made 2 other videos on the update of his self experimentation using B3, Metformin, and Statin. https://www.youtube.com/watch?v=nq-s7rDuLnc I feel that a statin is important and there is no reason to stop taking one because of muscle pain. I have been taking 500-1000 mg Acetyl L-Carnitine daily and you will no longer have any muscle problems. This has been used for years for this purpose.
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Van thanks for the video. how much statin do you take? Never heard of Acetyl L for the muscle pain. any study links?
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uzoma iwuagwu I take 5 mg Crestor. This gets my LDL to 70.
Just google the L Cartine for statin induced muscle pain. I use to get bad cramps in my legs. No more
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Van Thanks I will My LDL is 73 @1.25mg triglycerides at 49 so that's what I run.
I googled exactly as you listed but all the links talk about CoQ10 https://www.ncbi.nlm.nih.gov/pubmed/23190071
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I can't provide the exact source, but i did read that a man measured the rapamycin in
blood (taking I think 5mg/wk); He concluded only 14% got into the body; I am considering using sublingual; any thoughts anyone?
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In thee"Rapamycin for longevity: opinion article" by Mikhail V. Blagosklonny (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/) is stated: "The beneficial effects of rapamycin and CR may be additive, given that they are exerted through overlapping but distinct mechanisms. Intermittent rapamycin and CR (24-48 hours after) can be combined, to avoid potential hyperglycemia. Physical exercise may be most beneficial starting immediately after rapamycin use, to take advantage of rapamycin-induced lipolysis as a fuel for the muscles." Has anyone tried this approach?
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I think a reply will require a source for the 14% . Perhaps 14% is the amount he should have given what dose he takes. I personally have been taking 3mg sirolimus per week with Grape fruit juice (white) which equates to about 10mg/week and am age 66 and get 60 to 70% relief from arthritis if my hands.... Which has allowed me to titrate the dose properly in collaboration with Dr Green for the past 3 years. Plus one year on Pfizer's Rapamune previously. I've also occasionally done D+Q but with Fisitein not Q. I think this is more about delaying or perhaps preventing chronic diseases of aging as I've recently been diagnosed with a non aggressive prostate cancer. I mean to outlive the diseases that destroy what otherwise might be early retirement. Lost two uncle's within 2 years of retiring at 65..... Their wives left alone but well funded. I think as you try to properly dose Rapamune/sirolimus you should concomitantly drastically reduce A.G.E. foods or CR and Rapamycin are useless. Best of luck but search The Smithsonian magazine to see how Grapefruit juice is used with Rapamycin to reduce the overall it's dose but keep cmax levels where needed.... Although this was at very high doses for cancer therapy the principal is the same. Don't use the more easily found Ruby Red GF juice, use white for best effect and mind you don't overdose on your other meds due to the GF Juice!
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GEdwards Thanks for the Grapefruit juice tip!!! I looked it up and this is an interesting article regarding the combo;
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