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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Don Not too scary, since rapamycin's original large dose effect was to suppress the immune system.
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Rob8311 Rob, I agree. Evidently immunity suppression is the effect to be most concerned about.
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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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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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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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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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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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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 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.
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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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Iðunn
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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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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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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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David Michel What's a phenomena shot?
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