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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  • Thanks for the timely information.  My wife and I just started our first week of planned 12 weeks.  of rapamycin.  

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  • Hi Darryl,

    What dosage are you and your wife planning to take?

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  • Yesterday I found this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591294/ . The abstract includes the following: "We found that intraperitoneal (ip) administration of rapamycin after a tumor-resection surgery drastically increased the metastatic activity of 4T1 tumors. Possible correlation of this finding to human cancers was suggested by epidemiological analysis of data from Taiwan’s National Health Insurance Research Database (NHIRD)."

    I sent this to the LEF Wellness Specialists as a question about the mode of administration used in this study as opposed to oral ingestion. Here's a brief clip from their lengthy response: "... studies of this nature are not comparable to the anti-aging suggestions we provide because of the clinical dosages used which are much higher than the anti-aging dose suggestion... Although side effects are common in those taking a full dose of rapamycin to prevent organ transplant rejection, those taking doses suitable for anti-aging purposes are much less likely to experience side effects. However, care should still be taken to not excessively suppress mTOR as this can contribute to sarcopenia, frailty, and excess weight loss though again, this is much less likely at anti-aging dosages...  between 2-6mg per week and... individualized depending on individual response."

    I'm awaiting my first delivery of rapamycin. I intend to stay with the minimum dose with this initial supply, while monitoring my blood pressure, which is generally fine at present. I'll consider other tests later, especially if I also decide to take metformin. I'm hesitant about metformin at this time.

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      • Rob8311
      • Rob8311
      • 4 mths ago
      • Reported - view

      Don Not too scary, since rapamycin's original large dose effect was to suppress the immune system.

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      • Don
      • Don
      • 3 mths ago
      • Reported - view

      Rob8311 Rob, I agree. Evidently immunity suppression is the effect to be most concerned about.

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      • Rob8311
      • Rob8311
      • 3 mths ago
      • Reported - view

      Don The half life of rapamycin is about 60 hours, so a weekly dose suppresses mTOR1 but gives mTOR2 (the one you don't want to suppress) time to recover.

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      • Don
      • Don
      • 3 mths ago
      • Reported - view

      Rob8311 Thanks, Rob. That makes sense. Over the years I've kept up a general understanding of science while occupied in what may be called people work and finding personal pleasures outdoors and, intellectually, mostly in the fine and liberal arts.

       

      I rely on a pescetarian diet and daily walking with a bit of jogging and I avoid strong medications, even flu shots, which I haven't had in this century. When I start in on rapamycin I may supplement it with more vitamin C than usual.

       

      I'll still consider eventual low-dose metformin, along with a few other options. 

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      • Rob8311
      • Rob8311
      • 3 mths ago
      • Reported - view

      Don More vitamin C, and maybe also colloidal silver.  I've resisted using it because it's supposed to be a fad, but I have met too many people who rave about it.  One of my dogs has a predisposition to bacterial infection, which among other things affects her gums.  She was starting to have trouble eating.  After spraying her food with colloidal silver for a few weeks, my vet says her gums do not appear to be inflamed any more and she attacks food like she used to.  There don't seem to be many good options for dealing with a tendency toward infection, but maybe this is one.  Feel like I'm recommending snake oil, but...

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    • Don 

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    • Don I have been taking metformin 500mg over a year and subjectively feel more healthy, but I have also increased more vegetables salads but little exercise. No side effects.

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      • Don
      • Don
      • 3 mths ago
      • Reported - view

      are we there yet  So far the best medication I've ever found has been a diet high in vegetables and moderate exercise.

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      • Don
      • Don
      • 3 mths ago
      • Reported - view

      are we there yet As to metformin, the side effects may not be especially common in occurrence, or intense, but they sound pretty scary. 500 mgs sounds like a lot of anything. I wonder if low doses, for instance 100 mgs, offer any potential benefits.

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    • Don  The only caution I consider with metformin is taking daily b12 and coq10 supplements because they can be partially blocked.

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      • Don
      • Don
      • 3 mths ago
      • Reported - view

      are we there yet I take them now as they are essentials hard to obtain in food. One of the risk factors for serious disease is being over age 65, when liver and kidney functionality may be to some degree diminished. Gastrointestinal problems are listed as common side effects. Metformin may be no problem for people who are younger than I and/or in perfect health.

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      • Don
      • Don
      • 3 mths ago
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      Don By "risk factors" I'm referring specifically to Metformin risk factors.

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    • Don are we there yet LEF has several good articles on Metformin, here and here. In this article Bill talks about dosing to build tolerance - start with 250 once a day, work up to 500 after a week, then 500 with each meal after a few weeks. 

      The only gotchas AFAIK is to supplement with B12 and watch your testosterone as a man. If your testosterone declines (which it will anyway with age) then get a prescription for a topical cream - LEF has many articles on this. 

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    • Don LE recommends 500mg before each meal, with a protocol to start (250 once a day leading up to 500 each meal after a few weeks). Eventually it's suggested you can go to the maximum dose, which is like 850mg or something before each meal. Do a search on their site for into. 

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  • To clarify my view of flu shots, I avoid them simply because they dump a lot of clutter into the blood.

    Reply Like 1
      • Iðunn
      • Iunn
      • 3 mths ago
      • Reported - view

      Don What "clutter" are you worried about? In addition to "the four influenza strains recommended for the 2018-2019 Northern Hemisphere influenza season" and sterile water this year's Sanofi vaccine contains only:

      sodium chloride (4.1 mg),  monobasic sodium phosphate (80 mcg), dibasic sodium phosphate (300 mcg), monobasic 7 potassium phosphate (20 mcg), potassium chloride (20 mcg), and calcium chloride (0.5 mcg).  From the manufacturing process, each 0.5 mL dose may also contain residual amounts of sodium   taurodeoxycholate (≤ 10 ppm), ovalbumin (< 1 mcg), sucrose (< 10 mcg), neomycin sulfate 0 (≤ 81.8 nanograms [ng]), polymyxin B (≤ 14 ng), and beta-propiolactone (≤ 1.5 ng). A single  0.25 mL dose of AFLURIA QUADRIVALENT contains half of these quantities. ...

      Thimerosal, a mercury derivative, is not used in the manufacturing process for the single dose  presentation. This presentation does not contain preservative. The multi-dose presentation  contains thimerosal added as a preservative; each 0.5 mL dose contains 24.5 mcg of mercury  and each 0.25 mL dose contains 12.25 mcg of mercury.

      Aside from conceivably the thimerosal (which you can avoid by getting a prefilled single-dose vaccine), there's nothing concerning there at those doses unless you have a severe allergy to eggs or one of the other components.

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      • Darryl
      • Darryl
      • 3 mths ago
      • Reported - view

      Iðunn 

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      • Darryl
      • Darryl
      • 3 mths ago
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      Darryl 

      Thanks for the post about the flu       vaccine!  Do you know how close the vaccines match the existing strains?  I’ve read there is a very low percentage match from several sources. 

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      • Iðunn
      • Iunn
      • 3 mths ago
      • Reported - view

      Darryl Every non-conspiracy site I can find says the match is quite good (remember, sources dated last February are for last year's shot, even if they describe it as "the 2018 shot" — or else they're early guesses, well before the flu actually came around. You want sources from September and October 2018). Here's a sample:

      https://www.businessinsider.com/flu-shot-2018-effectiveness-availability-where-to-get-2018-9

      https://www.thedailybeast.com/last-years-flu-shot-sucked-this-years-could-save-your-life

      http://fortune.com/2018/09/29/2018-how-effective-is-the-flu-shot/

      https://www.youtube.com/watch?v=sz6LY5o5v_M

      (The CBC).

       

      In any case, a even a poorly-matched shot is better than no shot at all.

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      • Don
      • Don
      • 3 mths ago
      • Reported - view

      Iðunn Thanks for the detailed response. When I quit taking flu shots many years ago I was reading stories of formaldehyde residues in them and other stuff that sounded scary to a non-medical person such as I am. Perhaps the shots have changed since then, or I've changed my reading habits. My HMO offers shots from throwaway syringes, which I guess meet the definition of single doses, which I'll consider taking. I have other gripes about my HMO's medication protocols, not relevant here.

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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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      • Kerry
      • Kerry
      • 3 mths ago
      • Reported - view

      David Michel What's a phenomena shot?

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      • djmichel
      • CDR Phx
      • djmichel
      • 3 mths ago
      • Reported - view

      Kerry 😊 That is a pneumonia shot misspelled. 

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  • What is your age? Rapamycin is believed to be more noticably helpful in older ages.

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  • I am 76

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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
      • 3 mths ago
      • 1
      • Reported - view

      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
      • 3 mths ago
      • Reported - view

      are we there yet 

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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
      • 3 mths ago
      • Reported - view

      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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    • 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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  • 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). 

    Reply Like 1
  • 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). 

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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
      • 2 wk ago
      • Reported - view

      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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  • 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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  • 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
      • 9 days ago
      • Reported - view

      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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  • 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.  

    Reply Like 1
      • Rob8311
      • Rob8311
      • 9 days ago
      • Reported - view

      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
      • 9 days ago
      • Reported - view

      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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    • 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?

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      • Rob8311
      • Rob8311
      • 8 days ago
      • 1
      • Reported - view

      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.

      Reply Like 1
    • 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.

      Reply Like 1
      • Rob8311
      • Rob8311
      • 7 days ago
      • 1
      • Reported - view

      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.

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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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    • 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

      Reply Like 1
      • Rob8311
      • Rob8311
      • 8 days ago
      • 1
      • Reported - view

      Ellie You need to research Low Dose Naltrexone (LDN). A holistic Dr/Vet can prescribe. Very cheap. It's good for so many things. Just read the articles on Cimetidine being repurposed as a cancer drug on the LifeExtension.com site and you'll see what it can do. It is being integrated into anti-cancer protocols. My vet went to a regular vet conference and attended a class on using it. Among other things, it works against metastasis by preventing the cancer from jumping from the bloodstream onto the blood vessel walls!! This is in addition to the standard thing that antihistamines do, which is to counteract the emission of histamines by tumors to keep the immune system away. BTW, it sucks as an antacid. There is a website run by people who have cured their dogs of cancer with it. Both cimetidine and LDN are public so no one can make money off them, so like so many other great substances well funded studies are rare. Just Google these things and you'll be amazed. There is a whole community including doctors promoting LDN. Get the LDN book. I have been readingt studies for a while now. It is hard! But it gets easier. You just keep looking up the terms, and you take whatever you can get, even if all you can grasp is the conclusion. It might take an hour to read a paragraph, but the next time it will take less time.

      Reply Like 1
      • Rob8311
      • Rob8311
      • 8 days ago
      • 1
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      Ellie Just to see what an individual can do, go to this site: http://dognasalcancertreatmentforlucy.blogspot.com/p/tippner-protocol-for-dog-cancer-in.html. This guy saved his dog Lucy by researching. He doesn't take the time to credit much of the stuff on his site, and his web skills are minimal, but for a wealth of leads for cancer research for dogs (and humans) it's hard to beat. It inspired me to do my own research. Always scroll down because he uses a huge header that takes up the whole screen.

      Reply Like 1
  • Many thanks, Rob, have been digging through so much ino!  I am surprised I had not run into it before as I'm reading studies all the time.  I have a Biology degree, so it gives me a leg up on the scientific lingo, but you're right, it's still hard slogging!.. Anyway, many thanks for all the leads!  I am more hopeful now for the dog than ever!!!

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      • Rob8311
      • Rob8311
      • 7 days ago
      • Reported - view

      Ellie Yes! I needed the hope as well.  I'm so jealous of your degree.  If only I had known how much I would need such knowledge.  Fisetin should help with cancer as well, since the senescent cells it kills were put in that state as an anti-cancer mechanism and since senescent cells tend to promote cancer in surrounding cells.  There's a lot of buzz out there about CBD oil vs. cancer also.  Currently, my biggest struggle is against my 15 year old's IVDD and loss of hind leg function, so I am learning stem cells and physical therapy in addition to the rest.

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  • Best wishes to your dog as well!  Don't they become family for us!!!

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