Rapamycin Side Effect

Just read a recent addition to Dr. Green's site.  I'll just post part of what he says.  I don't get the impression he thinks it is a reason to stop treating, but important to be aware of.  He talks about his three years of experience with rapamycin treatment showing:

"Major side effect: Neutrophil Dysfunction

After almost 3 years of experience with weekly rapamycin, it has emerged that the major side is increased risk of extracellular bacterial infections. These bacterial infections are mostly skin and subcutaneous tissues. The risk is both increased frequency of bacterial infection and increased severity of bacterial infection 

Some animal studies showed rapamycin caused increased risk of death from pulmonary bacterial infection.

On the other hand, the function of the immune system, involving lymphocytes and antibody production is improved. In a recent study involving humans (Mannick, 2018) the risk of viral infections presenting as URI (upper respiratory infection was decreased.

The increased risk of infection from invading bacteria involves the innate immune system, which includes Neutrophils (also called polys) and macrophages (which engulf bacteria).  Decreasing activity of mTORC1 hinders the function of the innate immune system, especially NEUTROPHILS.

Consequently, In the skin and subcutaneous tissues, any onset of redness, pain, swelling, the cardinal signs of inflammation, should be considered as highly suspicious for bacterial infection.

Whle on rapamycin, anything suspicious for bacterial infection, should be considered as SERIOUS. Bacterial infection is especially serious to persons on rapamycin as there may be a decrease in the function of Neutrophils. ALL BACTERIAL INFECTIONS INVOLVING PERSONS ON RAPAMYCIN SHOULD BE TREATED WITH ANTIBIOTICS. In addition, rapamycin should be stopped until infection is totally eradicated.

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      • djmichel
      • CDR Phx
      • djmichel
      • 6 yrs agoSun. October 21, 2018 - 4:57 pm
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      This post make good sense.  I have been taking Rapamycin 5mg/Week for several years.  I did notice that when I get a skin cut or abrasion that it heals somewhat slower the it used to.  I was just relating this to aging, however Rapamycin could be the reason.  As precaution, I am going to: 1.  get a phenomena shot.  2. I may also move my dosage to once every two weeks ( 1st and 15th) to allow full recovery of MTORC1.  Hopefully in the near future someone will come out with a cost effective test to measure MTORC1 and 2.  

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        • djmichel
        • CDR Phx
        • djmichel
        • 6 yrs agoSun. November 11, 2018 - 2:27 pm
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        Kerry 😊 That is a pneumonia shot misspelled. 

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      • are we there yet
      • are_we_there_yet
      • 6 yrs agoFri. October 26, 2018 - 3:03 am
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      What is your age? Rapamycin is believed to be more noticably helpful in older ages.

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      • djmichel
      • CDR Phx
      • djmichel
      • 6 yrs agoFri. October 26, 2018 - 11:03 pm
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      I am 76

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        • are we there yet
        • are_we_there_yet
        • 6 yrs agoMon. October 29, 2018 - 1:41 am
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        Thank you. My greatest fear of Rapamycin is if intermittent use still correlates with cataracts. As has occurred with continuous use.

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        • Rob8311
        • Rob8311
        • 6 yrs agoMon. October 29, 2018 - 5:10 am
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        are we there yet Astaxanthin, Zeaxanthin, and Carnosine (eyedrops and capsules) really help.  I've stopped the progression in my 16 year old dog with those supplements.  Lutein and Bilberry probably help also.  Anything that works against glycation end products.

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        • Darryl
        • Darryl
        • 6 yrs agoSun. November 11, 2018 - 3:29 pm
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        are we there yet 

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        • are we there yet
        • are_we_there_yet
        • 6 yrs agoMon. November 19, 2018 - 12:56 am
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        Rob8311  Thak you rob...usefull...

        Also, is sirolimus or everolimus better at not supressing mtor2 but selectively focusing on  mtor1? Subjectively, does your use of rapamycin make you feel. Thank you for your self experimentation guidance to us all.

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        • Rob8311
        • Rob8311
        • 6 yrs agoMon. November 19, 2018 - 5:26 am
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        are we there yet Haven't looked into everolimus.  Is it even available?  Supposed to be better at leaving mTOR2 alone.  Haven't had anything noticeable from rapamycin.  I take it because it sounds like mTOR1 needs to be controlled.

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        • are we there yet
        • are_we_there_yet
        • 6 yrs agoWed. November 21, 2018 - 8:15 am
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        Rob8311 I think u r right. Everolimus is optimizes for immune suppression.  Note: Sirolimus can be bought for about $5.5 per 1mg pill with a 'goodrx' website free coupon.

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      • Danmoderator
      • skipping my funeral
      • dantheman
      • 6 yrs agoMon. November 19, 2018 - 1:34 am
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      In regards to the flu shot - I don't get it because I use getting sick as a biomarker of health. In this example, I haven't gotten the flu in many years. Basically when I really got aggressive with my health regime my incidence if illness went to nil. So in one sense, no need for a flu shot, and in another, if I started to get sick more frequently it would tell me something about myself. And maybe at that point, since I presumably would have a degraded immune system I would get the flu shot because I would need it (and I'd get more aggressive on immunosenescence) 

      Just a thought about it - purposely don't fix some things if I don't have to, so I can use them to gauge my health (such as not dying the grey out of my hair). 

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      • Danmoderator
      • skipping my funeral
      • dantheman
      • 6 yrs agoMon. November 19, 2018 - 3:22 pm
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      I posted elsewhere about this, but I'd remind people that if possible they should check they're CYP3A5 gene, available from Veritas Genetics and others. If you have the CC variant you may have decreased metabolism of rapamycin and require a lower dose (PharmGKB 2A). 

      Like 1
      • Ellie
      • Ellie
      • 5 yrs agoSat. February 2, 2019 - 10:12 pm
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      Re side effects of rapamycin.  What has anyone heard or read about mouth sores?  I am using it for my old dog and I think his mouth hurts.  Should I decrease his dose one time or more, or discontinue for a week or more?  Not info I can find on Google anywhere.

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        • Rob8311
        • Rob8311
        • 5 yrs agoMon. February 4, 2019 - 5:36 am
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        Ellie Would do both. Well known side effect, referred to as apthous stomatitis. Don't think it is too serious. Read https://rapamycintherapy.com/.

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      • Ellie
      • Ellie
      • 5 yrs agoMon. February 4, 2019 - 11:22 am
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      Yes, will do.  I emailed Dr Green, too, and he suggested the same tho I thought for a 100 lb dog, 2.5 mg would have been about right.  Obviously not, still learning...

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      • are we there yet
      • are_we_there_yet
      • 5 yrs agoMon. February 11, 2019 - 7:03 am
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      I am 71 dosing 4mg sirolimus every 10 days. 2 days after my last dose I developed an inflamed chest rash that has spread to shoulders but is slowing with antiseptic wash, Epson salt bath, antibacterial ointment and gold bond body powder as well as an oral antibiotic. Even Dr green had a similar problem and recommended early aggressive attention.

      still I am happy with sirolimus. For me, arthritis in left knee is over 90% gone. I expect further improvement when I self test with dasatinib in about 2 months.

      hope this helps other self testers. I recommend a strong antiseptic skin clinser in your bathroom if you use sirolimus.

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        • Rob8311
        • Rob8311
        • 5 yrs agoMon. February 11, 2019 - 4:28 pm
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        are we there yet Consider trying fisetin first. Dirt cheap, a flavonoid like curcumin, no known side effects, may be as effective. Amplify bioavailability with BioPerine from Swanson. Worked for me. Feel at least 5 years younger (I'm 67, 200 lbs). Dosed at 20mg/kg with no problems. Try less at first though. Study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/

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      • Ellie
      • Ellie
      • 5 yrs agoMon. February 11, 2019 - 10:10 am
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      Curious to hear how long you've been taking it.  Both the dog and I had only had two doses me 5 mg and him 2.5mg a week apart.  my mouth was different--not sores, but generally sore-ish and after skipping a week, resolving.  I will start again with 3.5 or 4 mg and will drop dog's dose too.  he has cancer I've treated with mega nutritional therapies for over a year, but am hoping the rapa will help.  I'm 74 and in great health, but old is less fun and functional than young.  

      Like 1
        • Rob8311
        • Rob8311
        • 5 yrs agoMon. February 11, 2019 - 4:30 pm
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        Ellie Don't overlook cimetidine (Tagamet). Lots of anti-cancer capability. Also, some cancers are completely shut down by Low Dose Naltrexone.

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        • Rob8311
        • Rob8311
        • 5 yrs agoMon. February 11, 2019 - 4:34 pm
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        Ellie Have been taking sirolimus 6 mg/week for about a year, no issues.  Dogs taking 1mg 3x/week for longer than that no issues.

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        • Danmoderator
        • skipping my funeral
        • dantheman
        • 5 yrs agoTue. February 12, 2019 - 1:42 pm
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        Rob8311 Regarding cimetide/tagamet - does it have anti-cancer effects? Bill Faloon has talked about this only in the context of immune system function AFAIK. The idea being that if you have a virus you can take that for a week only to boost the immune system to help it. You don't want to take it much longer, like many things in biology more isn't better. Anyhow improved immune system should have some anti-cancer effects but is it something that has been studied?

        Like 1
        • Rob8311
        • Rob8311
        • 5 yrs agoTue. February 12, 2019 - 4:44 pm
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        DanMcL See my reply to Ellie.  After I talked to my vet about it, he started giving cimetidine to everyone he knew with dog/human cancer.  Repurposing is getting more and more common.  LDN is a great example.  Naltrexone is something you give to prevent a heroin OD, and then someone tried it in low doses.  Rapamycin was used to suppress the immune system for organ transplants, and then someone tried it in low doses.

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        • Danmoderator
        • skipping my funeral
        • dantheman
        • 5 yrs agoTue. February 12, 2019 - 7:34 pm
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        Rob8311 My note isn’t about repurposing in general but how and ‘what for’ specifics. My sources recommend cimetidine for time restricted immune system boosting (a virus) and not as a general long term anti cancer.

        Like 1
        • Rob8311
        • Rob8311
        • 5 yrs agoTue. February 12, 2019 - 10:30 pm
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        DanMcL I don't remember how long cimetidine should be used vs. cancer.  Perhaps longer than the immune boosting, I don't know.  I read about the immune boosting and it is on my bucket list (so to speak), but there's a lot of material on cimetidine vs. cancer. When Ellie mentioned her dog has cancer I wanted to direct her to it.  You're right, the repurposing I was talking about is for cancer, not the immune system boosting application.

        Like 1
      • Ellie
      • Ellie
      • 5 yrs agoMon. February 11, 2019 - 6:01 pm
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      Many thanks, Rob, new info to me and I thought I was well informed.  Tagamet is easy to get, but do you know where to get naltrexone?  

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        • Danmoderator
        • skipping my funeral
        • dantheman
        • 5 yrs agoTue. February 12, 2019 - 2:09 pm
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        Ellie see my reply to Rob above regarding Cimetidine. 

        Folks, before taking anything do your research and make sure you understand it thoroughly. Some old advice for money: 'don't invest in anything you don't understand' also applies here.

        To help with this we are working on adding a Wiki for the site

        Like 1
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