I’d like to see evidence of this. I’ve got a surgery coming up in the next year and I 100% plan to stop raapmycin at least a month beforehand, and I don’t plan on taking it for months after.
Even if it did decrease the risk of sepsis, the catabolic effects would interfere with recovery.
I don’t think you will find a study about surgical infections and Rapamycin. And it may not show any difference but you are already stopping it so why does it matter? Which is why the study won’t get done, not to mention the number of people on Rapamycin is small (no published number).
Dr. Greene reported more skin infections on low dose weekly Rapamycin. (Full text reference not available)
Anything that would interfere with wound healing would be rationally stopped around the time of surgery. Rapamycin has been discussed as a CR mimetic, which it obviously isn’t exactly, but you should not CR around the time of surgery. May not be a study to say it is harmful but there are lots of studies about adequate nutrition and protein intake around the time of surgery and the needs are much higher than baseline.
In some Rapamycin raises blood sugar which is a known increased risk factor for surgical infections. The stress of surgery causes the release of cortisol which raises blood sugar.
The reality is that studies have shown other similar medications do and do not increase surgical infections if maintained throughout the recovery period. So Rapamycin may not make enough of a difference even if it was studied. Methotrexate comes to mind as that is used in large numbers by people with RA who get joint surgery. In this case, inflammatory arthritis can flair with holding the medication so there is a significant short term risk that has to be balanced.
We take Rapamycin and other things based on incomplete data. I would argue that any immunomodulatory drug can be an immunosuppressant in some situations. The benefits are unclear as are the risks. Everyone who takes Rapamycin does it without a RCT showing longevity benefit. To require a RCT that shows a specific risk or harm is a bit unfair I would think.
Both of these are higher dose in patients with a significant disease. The pneumonia risk is why I think flu shots and pneumovax are just common sense adjuncts. I mean they are for anyone so it isn’t really a stretch. But if you want I can provide references that vaccines reduce risk of death -
48 WK study with higher infections 2-6 mg a day
48 WK study (2nd run of 48 WK - extension study) with 2 treatment related deaths from sepsis. Some discontinuation of treatment and dosage adjustments because of pneumonia.
I think I worded the statement about reducing risk of sepsis poorly. What I meant is that flu vaccine and pneumovax reduce risk of sepsis from pneumonia by close to 50%. Pneumonia is a risk after surgery. Vaccines and withholding Rapa probably get that to a full 50%. So claiming a couple percent benefit from withholding - something which will never be proven.
What I would say about surgery is to ensure the rapamycin trough is zero before and not take it until the wound is healed.
Matt Kaeberlein is probably the most highly regarded researcher when it comes to rapamycin and the Mtor pathway. I find it difficult to believe that if sepsis whether you’re a transplant, patient or a weekly doser was a major consideration he would have addressed it. I definitely saw a decrease in my immune response to wounds and cuts.
The mortality paradox is that transplant patients have a lower mortality rate from sepsis (8.3%) than non-transplant patient (12.3%). Only one to 6% of transplant. Patients are given rapamycin as their primary treatment.
What I find frustrating is researchers such as Dr. Stanfield compare daily(2-6)milligrams daily to weekly use failing to mention the wide disparity in dosage
Right, the things that kill you in sepsis is partly the bodies response. Arguably it is the bodies response but it is hard to tease out. Certainly infections kill if the body doesn’t respond at all so there is an appropriate amount of response and our bodies aren’t perfect at it.
So steroids (corticosteroids) increase the risk of sepsis but are used to treat sepsis. Rapamycin could be the same. Now, steroids are different because they are basically the same as cortisol and you need to increase cortisol in the setting of sepsis and the data seems to show that most people don’t increase cortisol enough.
So it is a paradox but not one without an explanation ans it is seen in transplant patients on various regimines. There is also a potential confounder that transplant patients may be more likely to be diagnosed with sepsis despite a very definite criteria. More diagnosis leads to lower mortality.
Where are the numbers you quoted from when you say Rapamycin was the primary treatment? You mean the primary anti-rejection treatment? I only ask because multiple drugs are used routinely - although I am sure there are subsets with only Rapamycin. That would be a helpful subset to look at.
I think sepsis or infections should always be mentioned when discussing Rapamycin and the significant difference between transplant dosing and longevity dosing.
Although the search did not elaborate what other drugs were used, I can only assume that there were others, and that rapamycin was the primary drug
Although not, explicitly stated, the article seemed to imply that rapamycin was never alone and always used with other anti-rejection medication.
Google searched rapamycin and sepsis
What I remember from years ago with tacrolimus was that initially it was always multiple drugs - typically cellcept, tacrolimus and steroids.
Over time, it tapered down and went to mono therapy often enough (mostly tacrolimus). But sepsis was certainly more common early on with higher doses and triple therapy. Negative studies are less fun so I imagine they typically looked in the early times.
There is a cohort of 50 patients on Rapa maintenance as mono therapy and no mention of sepsis. They were 7 years out from transplant and followed for a few years. 4 deaths but preexisting stuff.
So the monotherapy cohorts do exist. But not huge numbers. Most used when there was a problem with tacrolimus.
And just to be clear. Tacrolimus shares nothing with Sirolimus other than the name but they are both used for anti rejection.
Sorry for my delayed response. Those statistics were all transplant patients. If I remember correctly, it was a small percentage of the transplant population 6%. I believe that was using rapamycin as the primary anti-rejection medication. Please don’t give too much Creedence to my Numbers they’re straight off Google.
I’m prompted to share one of my more bizarre experiences in my elaborate and complicated medical history.
I was born with an aortic bicuspid valve. At 21 I was misdiagnosed. I had advanced endocarditis, but it was missed in my blood work and I was released home.
After six months, I was so sick. I could barely get myself to the hospital. When I arrived at emergency, I told them. I was having an episode. The RN told me to lay down and shut up three seconds later after realizing I had a heart rate of 240 bpm. He was massaging my arm and bells were ringing.
After six weeks of antibiotic IV therapy, I was released.
Six years later, I contracted endocarditis once again. After reviewing my echo, I had a semicircle of cardiologist around my bed telling me they were transferring me to downtown LAUSC for emergency open-heart surgery the next morning to replace my bicuspid valve that had developed a septic cyst.
I calmly asked the obvious head guy what were my chances if I declined surgery and went for the IV antibiotic therapy one in 10? He looked at me rather strangely and definitively said no I then asked him one in 100? He then got a very perplexed and irritated look on his face and having some math awareness had to admit yes. I told them at that time I will take those odds.
Six weeks later, an echo revealed the cyst had either dissolved or been absorbed. I limp along with that original bicuspid valve another 18 years.
Sorry that was limped. I had a organic valve replacement 18 years later.
Just so you know what you’re looking forward to getting sick at 60 is a cakewalk to getting sick at 70.
Just a quick note anecdotally I started rapamycin treatment at 69. At that time I was starting to feel a lot of the usual age decline.
Before I tell you anything about miraculous changes, I have to say at the same time I started taking rapamycin. I also started fasting 20 hours a day and eating nutritionally, dense natural food, lifting weights, walking 3 miles a day and doing push-ups.
Within 4 to 6 weeks, I experienced amazing benefits, both cognitively, and physically. I have arrived at the same conclusion as Matt. The more you suffer from age related decline, the greater the comparative improvement from rapamycin.
Oops, forgot to mention a dramatic improvement in my sleep and a certain circadian awareness
Wow, your story is inspirational. And ha on getting sick at 70 vs 60!
Regarding your dramatic improvement in sleep… yeah, I believe it!
As many here already know, that was the single biggest thing rapa did for me… it cured my lifelong insomnia! I didn’t even know that was possible.
I’m a different human on rapa, but of course it’s probably because I now sleep!
It seems like after two years I am still discovering daily miracles from this intervention
Just watched a podcast featuring Professor Richard Miller, who claims to have some role in the intervention testing program. I can’t believe that he would sacrifice his credibility by. fear mongering rapamycin.
What amazes me about supposed experts like Miller and Stanfield they are either incredibly ill informed or intentionally, ignoring the monumental evidence of high dose rapamycin use in the transplant population.
Comparing the suggested 6 mg weekly to every day use from 3 to 5 mg is ridiculous in itself. but by ignoring that the evidence is overwhelming that there are serious, but non-life-threatening side effects to this drug is misleading.
I suspect that there are thousands of 70+ year olds who practice a diligent exercise nutrition, and sleep protocol and have added rapamycin to their protocol have experienced noticeable, if not miraculous results. for us, the risk reward debate is a no-brainer.
What podcast was that?
It was called the testing the longevity promise what mice can really teach us about slowing aging it also featured Doctor Macuse Jacques and doctor Raghav Seggal.
A link would help as there are lots of platforms that do podcasts.
There are, however, range of views on different interventions not only rapamycin