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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    • djmichel
    • CDR Phx
    • djmichel
    • 4 yrs ago
    • Reported - view

    I have been taking 5mg Rapamycin for the past two years.  Recently had a lesion on my forehead that turned out to be Squamous Cell Carcinoma.  My Derm who is a young guy and a Mohs surgeon, said he though that the squamous cell may be related to Rapamycin.  He said that when he was a resident they saw a number of folks taking Rapamycin for transplant and they had a large number of Squamous Cell Carcinomas.  He did say they were taking Rapamycin daily and they had a "lot of Leisons".  He said to be careful as he surmised that Rapamycin may slow the immune system down ever so slightly and any propensity to developing skin cancer may be aggravated.   Has anyone run into any potential immune problems?

    Like 1
      • GEdwards
      • GEdwards
      • 4 yrs ago
      • Reported - view

      djmichel I'm recently in the higher numerical half of his 60s, male, fair skinned, 99.7% norther eurpean decent. And actually have seen studies showing that Rapamycin (taken intermittently) will boost your immune system. https://www.ncbi.nlm.nih.gov/pubmed/25540326 as this study shows.
      And it is being considered as a supplement to the flu vaccine as it enhances the immune system response.  I'm just at my third year of rapamycin use and 18 mos into using it with metformin etc.  mtor1 pathways are 'exquisitely' sensitive to rapamycin and mtor2 (primary immune response pathway) is not.  Only by daily dosing of rapamycin, which builds the rapamycin up high enough to surpress mtor2 (primary immune pathways) does it lower overall immune systems....and it is used this way (daily) to avoid transplant rejection.  Surprisingly, the experience of transplant patients using cyclosporine to suppress the immune system for transplant anti-rejection purposes sees about 50% of patients developing skin cancer..... BUT when using rapamycin in higher doses this for this same purpose.....lower than normal rates of skin cancer are seen.  Now rapamycin is being tested for its anticancer properties.  As someone (fair skinned and abused the sun) with a close personal relationship with my dermatologists liquid nitrogen for may years before I started rapamycin and having a melanoma (in-situ) recently removed I am acutely aware of the risks.  So three years in, I've read on this obsessively and I am very comfortable with rapamycin and consider it to strongly (or even mildly) reduce my cancer risk profile.  

      Like 4
      • Gokhan
      • Gokhan
      • 4 yrs ago
      • Reported - view

      djmichel Two related papers:

      http://ar.iiarjournals.org/content/29/6/1927.full

      https://www.ncbi.nlm.nih.gov/pubmed/26138646

      "488 were exposed to sirolimus and 47 developed an incident SCC."

       

      SCC risk with Rapamycin sounds fairly real... even with weekly intermittent use based on your experience. (we have to go with N=1, as majority of things we're doing here is an extrapolation from basic science + N=1).

      Like 1
      • Gokhan
      • Gokhan
      • 4 yrs ago
      • Reported - view

      djmichel Hope you're doing well. Sorry to hear about the SCC. Given everything you've shared on this forum, I see you as a pioneer. Thank you so much! Have you stopped using Rapa? I was just about to start it :/ SCC risk, with prolonged use, seems real.

      Like 2
    •  Gokhan The papers you cite, and the general knowledge regarding immunosuppression in solid organ transplant recipients indicates very strongly that Cyclosporin (Sandimmune) is responsible with up to 16% of transplant patients treated with this drug getting SCC, many with catastrophic SCC. That is, multiple lesions with high grade of metastisis. The use of sirolimus as an adjunct to cyclosporin does not increase this incidence. Rather, when comparing tacrolimus (calcineurin inhibitor) to sirolimus adjunctive therapy in organ transplant patients on cyclosporin, the SCC's in sirolimus are less thick, less vascular, and less aggressive. The 47 patients out of 488 transplant patients in the Kaiser Permanente retrospective study is consistant with SCC incidence in solid tumor transplants treated with cyclosporin (the mainstay of transplant immunosuppression). Please read the following two statements carefully as it comes right out of the study you cited "SCC risk was not associated with ever use of sirolimus (adjusted hazard ratio 1.18, 95% confidence interval 0.84-1.16) or cumulative duration of sirolimus exposure (adjusted hazard ratio 2.75, 95% confidence interval 0.84-9.04, comparing long-term users with nonusers). "Among a large cohort of SOTRs, sirolimus exposure was not associated with a reduction in incident posttransplantation SCC risk."

      This study simply states that sirolimus does not reduce the high incidence of SCC in transplant patients, nor does it increase it. Other studies, such as your first citation above indicate that SCC in organ transplant patients treated with sirolimus versus tacrolimus show less vascularity and thickness of SCC. Less vascularity would be consistant with sirolimus known inhibition of angiogenesis and a less vascular tumor is generally smaller and less prone to metastasize

      Extrapolating broad conclusions such as "rapamycin causes SCC" from reading studies of transplant patients recieving immunosuppressive therapies which include rapamycin is what happens when the reader does not possess a broad clinical/scientific background. In order prove the hypothesis that rapamycin causes SCC, long term studies of otherwise normal people, with a cohort in the many thousands taking rapamycin, versus a cohort not taking rapamycin, and controlling for relative sun exposure and fairness of skin (among other things) would have to be performed. This study will never be done. As it stands, the way I read the literature is that in patients with the highest risk of SCC (transplant patients treated with cyclosporin), sirolimus does not increase incidence of SCC but may reduce severity via decreased vascular supply, thickness, and aggression. I can't see how any other conclusions are possible. 

      Like 7
    • Mark Thimineur Thanks for posting. I was gathering the same thing and wondering why the OP posted as he did. 

      Like 1
    • uzoma iwuagwu 4 million basal cell carcinomas, 1 million squamous cell carcinomas, and 200 thousand melanomas are diagnosed yearly in the U.S. Over 90% of these are due to exposure to non-ionizing radiation (sun). Having 5 sunburns doubles the risk of melanoma, just one sunburn in childhood doubles the risk later in adulthood. SCC is 100 times more prevalent in transplant patients.

      The sun exposure issue is one of concern as most of us baby boom generation have had multiple burns in childhood and many of us have spent long hours in the sun through adulthood. My view on sirolimus use currently is that there are thousands of experiments indicating a general antineoplastic effect, which includes skin cancer. I have posted previously that in vitro studies of skin exposed to non-ionizing radiation indicates (at least in vitro) a protective effect of rapamycin on the many damaging effects of sunlight on skin. I noticed last summer and through the caribbean yachting season this year (cut short by pandemic) that I was more resistant to sunburn and needed less sunblock. That is why I began looking into possible protective effects of sirolimus from solar radiation and discovered that study.

      I actually feel pretty positive on my use of sirolimus as it relates to antineoplastic effects including that caused by far to much sunlight exposure over my lifetime.

      Like 3
      • djmichel
      • CDR Phx
      • djmichel
      • 4 yrs ago
      • Reported - view

      Gokhan Doing well, thank you for asking.  I am still on all of the life extension protocols and take 3.5 mg Rapamycin once a week and am getting ready to do another D+Q round shortly.  I think it is important at this time to take additional Vit. D3, of which I am taking 5K a day, in-addition to my regular regimen of supplements. So far OK, which reminds me of the guy who jumped off the Empire State Bldg. and as he passed the 60th floor he saw someone at a window and yelled, "So far OK"

      Like 2
      • Gokhan
      • Gokhan
      • 4 yrs ago
      • Reported - view

      Mark Thimineur Thanks for the more careful analysis. I feel this is definitely worth the discussion. I'm glad you took the time to post a detailed response. Thanks!

      Like 1
      • Gokhan
      • Gokhan
      • 4 yrs ago
      • Reported - view

      A response to the 2nd study I shared: 

      https://www.jaad.org/article/S0190-9622(16)00067-0/fulltext

      It basically says that this analysis isn't quite meaningful due to very powerful confounders such as other immunosuppressant use. 

      Like 1
      • GEdwards
      • GEdwards
      • 3 yrs ago
      • Reported - view

      djmichel I wonder if this discussion has reviewed the differences in the innate vs the adaptive immune response and exactly what the sirolimus affects?  And consider that affect in light of the Mannix study showing flu shot response is enhanced ~20% in seniors that had sirolimus dosing prior to the vaccination.  Also I have seen papers showing the vast reduction in skin cancer issues for transplant patients on sirolimus vs traditional immune suppressors.....  Lastly, I would remind some that sirolimus is being used as an anticancer drug in high doses and I take it with grapefruit juice weekly using caution that any other meds I've ingested were taken ~4 hours prior to the GF juice.........this approach makes my 2 mg dose weekly worth more for less $ which is an issue for me....  https://www.oncologynurseadvisor.com/home/headlines/web-exclusives/grapefruit-juice-harnesses-power-of-sirolimus/

      This was discussed more thoroughly in the Smithsonian and a better discussion might be found there.

      Like 1
    • djmichel
    • CDR Phx
    • djmichel
    • 4 yrs ago
    • Reported - view

    I take 5mg weekly.  Certainly not daily. 

    Like 1
    • djmichel
    • CDR Phx
    • djmichel
    • 4 yrs ago
    • Reported - view

    Actually I just recently learned what I though was 5mg weekly has turned out to be 3.25mg due to a compounding error by the producer of RapaPRO, one of the suppliers that was recommended here by a member.  Now all of their Rapamycin products are labeled 3.25mg.

    Like 1
    • djmichel I think that place turned out to be selling sugar. 
      I've been on Rapa over a year. Started at 2mg and I'm up to 12mg/wk. I didn't notice a change in white blood cells til 8-10. I'm still in range but lower than I was. Anecdotally I get sick a lot less so IDK. I lower weekly dose when traveling.

      Like 1
  • I have read in various place that mTOR2 will also be inhibited after long term treatment with rapa;  However, I can't find any info. where this would lead;  

    Like 1
      • GEdwards
      • GEdwards
      • 4 yrs ago
      • Reported - view

      Hi Patrick Stanley mTOR1 and 2 respond completely differently. mTOR is responsive (exquisitely it is said) and can be suppressed with only intermittent dosing whereas mTOR2 requires high stable blood levels of an mTOR suppressant to respond and be effected... Eg daily dosing.

      Like 1
      • David H
      • David_Hanson
      • 4 yrs ago
      • Reported - view

      Patrick Stanley If you google search for mTORC2 and Rapamycin you will find links to many research papers which to me are hard to understand. But you might want to read this post on fightingaging plus the comments. https://www.fightaging.org/archives/2019/08/a-caution-on-mtor-inhibitors-loss-of-mtorc2-in-the-hypothalamus-harms-mice/

      Like 1
  • thank you for your efforts and advice!!  Do you know the results of mTOR surpression?

    Like 1
  • 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.

    Like 10
      • Karl
      • Karl.1
      • 4 yrs ago
      • Reported - view

      Mark Thimineur 

      1.  I’m having trouble coming up with a mechanism by which rapamycin would treat psychiatric illness. Any ideas?
      2.  How much concern do you have about malpractice using a powerful drug for a non approved reason?

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    • Karl

      As to the psychiatric effects: there are pretty profound effects on neurotransmitter concentrations and behavior observed in rodents Neuroscience. 2012 Oct 25; 223: 102–113.   "Our studies show that rapamycin enhances cognitive function in young adult mice and blocks age-associated cognitive decline in older animals. In addition, mice fed with rapamycin-supplemented chow showed decreased anxiety and depressive-like behavior at all ages tested. Levels of three major monoamines (norepinephrine, dopamine and 5-hydroxytryptamine) and their metabolites (3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid) were significantly augmented in midbrain of rapamycin-treated mice compared to controls. Our results suggest that chronic, partial inhibition of mTOR by oral rapamycin enhances learning and memory in young adults, maintains memory in old C57BL/6J mice, and has concomitant anxiolytic and antidepressant-like effects, possibly by stimulating major monoamine pathways in brain. "

      As for malpractice concerns I always am congizant of risks but often make use of off-label treatments for some pain management issues: Example: Ketamine infusions. Having observed rapamycin effects in myself and some family members, I have some confidence in the relative safety of well monitored use. Animal studies on neuropathic pain (neuropathy and sciatic ligature models of peripheral neuropathic pain, spinal cord injury models of central pain) show rapamycin has consistent and significant pain reducing effects. Rapamycin studies on rodents made opioid tolerant indicate mtor inhibition affected both the tolerance and the hyperalgesia. There are also scholarly articles describing benefits in crohns, RA, and multiple sclerosis. There is enough here to justify using this drug to treat patients who are doing poorly despite all possible on-label treatments (opioids, anti-depressants, anti-convulsants, spinal cord stimulation, intrathecal opioid pumps, behavioral treatment, spinal injections, nerve blocks etc). 

      Observations of benefits in humans with severe disease and disabilities seems to fit the biology of mtor inhibition seen in the experiments using rodents. It is quite interesting to me.

      Like 6
      • Karl
      • Karl.1
      • 4 yrs ago
      • Reported - view

      Mark Thimineur Thanks for all the info, and thanks for what you do.  Pain management must be one of the most challenging specialties in medicine.

      Like 1
      • Larry
      • Larry.1
      • 4 yrs ago
      • Reported - view

      Mark Thimineur Amazing, thank you for your work and posting. 

      Like 1
    • Karl   Rapamycin has a profound effect on monoamine neurotransmitters.  Odds are this is related to its affect on pain, anxiety and mood. 

      https://www.ncbi.nlm.nih.gov/pubmed/22750207

      Like 1
      • MAC
      • MAC
      • 4 yrs ago
      • Reported - view

      Mark Thimineur A recent paper on Rapamycin and telomeres

      Rapamycin worsens diseases and premature aging in mice with short telomeres

      https://www.news-medical.net/news/20200303/Rapamycin-worsens-diseases-and-premature-aging-in-mice-with-short-telomeres.aspx

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    • MAC It's too bad the study doesn't go into better detail. I'd be curious as to how they dosed the subjects. MTOR1 and MTOR2 could each have a varied affect but as we take it, we don't inhibit 2

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