Rapamycin and Injury

I strained my hamstring badly in May ‘21 and despite a lot of physio and rehab it’s still not recovered. I’m starting to think Rapamycin might inhibit the healing process? There are certainly pointers towards that in the literature… but interested to hear your takes.

I will share something that may be a similar situation. I am stopping Rapamycin temporarily 14 days before oral-maxillofacial surgery (done by a MD/DDS professor) during wound healing personally and giving it time after as well, on top of my recent bruising. I do not want a weak spot because of delayed wound healing.

And I already have my own cocktail for wound healing using similar pre, peri, and post-op nutrition and immunonutrition strategies (with some of my own additions) to MD Anderson’s handout crafted by PhD/RDs. What I can say is the state of nutrition interventions surrounding oral surgery seems pretty poor especially since a dentist (DDS with apparently just enough oral surgery experience to do it) wanted to yank out my M3M that was near the IAN and his patients got no advisory on any nutrition to speed the process. Only when I did a ton of research and got a third opinion did I figure out coronectomy was the best possible option to preserve my IAN that none of the general dentists ever mentioned. And the professor surgeon guy also had a full handout on nutrition and all the no-no’s around the surgery - which includes people to stop anything immunosuppressive ie smoking not even for one day or they’ll cancel the surgery. That included rapamycin. Since @David is somewhat more on the surgery side of things it seems especially with much more surgical experience and his son going to surgery (I can do simple I&D, delivered a few babies, and simple stitching with meh handiwork at best - not much surgical experience beyond that), maybe he would know better and can point to some of these issues surrounding the healing process that I missed.

Any type of healing process I’m fairly certain one needs to consider stopping rapamycin temporarily, but not 100% sure.

Never strained a muscle because I watch my form very carefully (I have a biomechanics guy and bought a mirror thing that watches my form - I also have gait analysis and careful with shoe selection) as I view exercise as a no-brainer with dangerous tradeoffs if I get an injury, especially when I get near 90-95% 1RM.

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@tongMD @Maveric78

I can offer speculation, but not sure its worth more that the points you both brought up. Hamstrings are a tough injury to recover from.

My undergrad was in Sports Science and i dabbled in the world of strength and conditioning coaching while I ran track as a decathlete. My worst hamstring injury was racing my kid years later (48 y/o). After audible “pop” it never seemed quite right. 10 years later (now at 58 y/o) I started Orange Theory with a power walking approach to the treadmill due to the hamstring injury. Over time I started jogging and then running as the hamstring scar tissue loosened. I started taking Rapa about 3-4 months ago and I noticed soreness and recovery massively improved. Hamstring working now to full all out sprints with no signs of my previous injury.

The balance of damage and repair from injury and or aging is probably not far off. As surgeons ( the good ones :wink: ) we pay attention to improving outcomes by preventive actions before surgery - during surgery - after surgery. One of the most important approaches is controlling the bodies healing response (or over response). Using anti-inflammatory techniques, anti-coagulants to help prevent excess blood clotting and even anti-histamines.

@Maveric78 Here is my guess for you (only a guess and not medical advice) Rapa has nothing to do with your injury not healing, but I could be totally wrong. If you were taking it for a kidney transplant and on immunosuppressive dosing, then yes, it could totally be an ingredient.

@tongMD - With your extremely high intellect and methodology for risk vs. reward, going with what your conclusion is probably right. I don’t think the Rapa would harm your procedure results and could make arguments both ways leaning more into fact that we do not have enough data and taking break would make the most sense.

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1 rep maxes are fine for athletes and young people to help determine load percentages, but may be overrated especially in older people where your risk to reward starts to narrow.

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Haha, thank you for the compliment. I’m not really certain. Just a guess.

Since I wasn’t precise enough - I want to point out for clarity for everyone here that I was referring to an “acute healing process” (which as you well know, has post-op infection risks that also interfere with wound healing but that wasn’t my main concern with rapa using my current understanding of just simply isolation/decolonization/other ID preventative manuevers with abx + noninterfering synbiotics first 7 days) especially in my personal case just to illustrate for some ideas to talk to a physician - say preop carb loading 12 hrs before, within 4 hrs-24 hrs after surgery eating high enough liquid calorie/protein + select micronutrients + immunonutrition while balancing infection risks (in my case dry socket). These may apply to the pre-injury and post-injury phases.

I also added a few natural and prescription appetite stimulants (ie gabapentin) that don’t interfere which I consulted with an expert to reduce the use of opioids post-op for multimodal pain management. Pain does indirectly relate to healing. Hopefully, it’s just minimal acetaminophen, limited liquid ibuprofen, and gabapentin 2 hrs before sleep for me personally. But if I have to - hydrocodone/apap 5-325 while accounting for previous use (I happen to also have NAC on hand). But just to be clear, there’s just way too much going on in surgeries that I may have missed or doesn’t translate to strains. It’s just something I talk to with the right team of experts, so we have a solid plan with the best possible information available at the time.

Back to what could be of interest to further look into and to further describe my clinical reasoning in my own case - preventative maneuvers for malnutrition and such on top of getting the right amount of the first inflammatory phase plus neutrophils in wound healing are all kind of opposite to mTOR inhibition and possibly mild neutropenia. Then there’s the acute fibroblast stuff later on with collagen synthesis as we are aware in pretty much any wound or scar, I’m pretty certain I don’t want to mess with mTOR inhibition on collagen synthesis at least the first 14 days or so post-op.

From my understanding, if I had chronic inflammatory joint/capsule disorders, or tendonitis/similar stuff or had some chronic strain say a year ago (while not on rapamycin during the acute phase) that could be age based - on top of based on my medical history, genetics, drug regimens, and other clinical factors, I would run a trial of rapamycin in my situation instead of withholding rapa. But I could be wrong - maybe rapa could fit in the acute processes somewhere. Just what I’d do in my situation and not medical advice. I have no strong proof to the nth degree evidence here that insurance companies would cover. All I have is theories and at best some things that have some suggestive evidence or enough to make a weak recommendation in my own medical situation with high safety in mind.

I think your example with a ~10-year injury seems to fit in what I’d consider “chronic” and possibly “age-related” but I haven’t really taken a look at the records and did a PE to really form a strong opinion. Just figured it would be helpful to point out for clarity so people have some things to think about it, can talk to their doc about it for a shared decision-making process.

Love Orangetheory’s shock absorption treadmill and fun trainers, so me and my SO can go together btw. Only thing I just don’t like is the volume of music they use - had to remember to wear specialized earplug filters to drop the dB to safer levels and avoid possible dementia risk.

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I love Orange Theory! I walk out completely spent with 1,000 - 1200+ calories burned. Agree about the treadmills.

Preop - Find a healthy patient :wink: If possible reduce inflammatory physical responses - smoking, sugar control, dental organisms and well rested before the procedure.

Op - pre op antibiotics if needed, pain control with site injections, sterile prep, bleeding control with epi - and good surgical technique. Efficient surgical time to minimize anesthesia time. Some like antihistamines, steroids, and anti-inflammatories - not any with good evidence.

Post Op - anti-inflammatory options (ice, NSAIDS), chewing gum - to restart GI system, sugar control to improve healing tissue, ambulation when able to restore good blood flow,

These are just some off the top of my head norms from day - probably many more to add.

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Sorry, you have so many physical issues.

Because of the opioid epidemic, doctors are very reluctant to prescribe opioids for pain management. My dentist just flat out refuses to prescribe them because he feels
acetaminophen plus ibuprofen work just as well.

I totally agree. I have had three hernia operations over the years and was given a script for
Percocet for the first two surgeries and nothing for the last one. My doc told me to take acetaminophen and ibuprofen. I actually like the combo for pain relief than Percocet.
Then if that is still not enough I add some gabapentin.
People really like opioids for the “comfortably numb” feeling they produce and like to use them even if they have no pain. IMHO, opioids are overrated for pain relief.

Sorry for all of the references. I have to use them to support my layman’s opinion.

Conclusion: Gabapentin and ibuprofen independently alter the facilitated state as measured by somatomotor and autonomic response. Together these agents interact in an additive fashion if delivered concurrently. This combination may prove useful in managing postinjury pain states in humans.
Evaluation of interaction between gabapentin and ibuprofen on the formalin test in rats - PubMed.

Five hundred milligrams (mg) of acetaminophen given with 200 mg of ibuprofen is more effective than opioids for postoperative pain and dental pain, research has shown, and the combo causes fewer side effects, with essentially no risk of addiction. NSAIDs are good even for excruciating kidney stones and minor fractures.Nov 1, 2021
https://www.scientificamerican.com/article/advil-tylenol-and-similar-painkillers-used-to-replace-opioids-carry-risks/#:~:text=Five%20hundred%20milligrams%20(mg)%20of,kidney%20stones%20and%20minor%20fractures.

A Randomized, Controlled Trial Comparing Acetaminophen Plus Ibuprofen versus Acetaminophen Plus Codeine
AcIBU is a safe, effective method of pain control after outpatient breast surgery. Compared to T3, it provides at least equivalent analgesia and has a more tolerable adverse effect profile.

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It’s not that bad compared to much bigger surgeries - just sideways impacted wisdom teeth on all 4 sides (IAN touching on bottom 2) and younger “healthy” patients tend to have it much better on the healing side of surgery (although I’ve seen “healthy” 50 y/o and “unhealthy” 30 y/o) - I suspect I may only need opioids for the first day if the pain is not controlled with nonopioids.

But yeah the opioid crisis basically made it difficult to prescribe loosely, enough nurses are telling me some patients are just trying to get pain pills (and they could be right, I take their opinions very seriously when they’re spending more time than I am), but I personally believe in giving one time benefit of the doubt, as long as not clearly doctor shopping/other clear signs. I’m pretty sure I have the option for opioids just in case from the oral surgery consult. Chances are I won’t use it though from the stats I ran (highly variable and all over the place)

Plus, I need to get rid of these M3Ms (don’t want to wait until age 32+ based on some suggestive bone-related evidence) to maximize oral health since it’s hard to clean with sideways impacted eruption. Better to avoid the possible situation of getting infected from teeth and then sepsis while on rapamycin in the future - even if it’s uncommon based on risk factors - and the teeth are highly correlated to CVD. Unfortunately, it’s been difficult to find a dentist that is familiar with rapamycin and doesn’t scan me with panoramic/bitewing X-rays all the time because of solid evidence of thyroid side effects and suggestive evidence of other side effects over decades. Too many dentists refuse to see me without frequent X-rays, even when explaining the issue and my risk factors showing it’s literally not indicated every 6 months. Have to end up seeing them every 2 years instead and simply use other methods such as tea intake, berry intake, guava leaves, specific biodegradable bamboo floss, and specific electric toothbrushes

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Yes, unfortunately, even though you are a doctor, like me you are just a layman to the dentist. That’s why I have to take some of my healthcare into my own hands. My doctor is a good man but isn’t interested in my medical opinions.
BTW, I use a university medical center and in the waiting room, there is a posted sign: “We do not prescribe opioids”
This is becoming more common.

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Unfortunately, our medical system does this. Years ago, if you did not treat patients with narcotics, you were breeching a standard of care and some threats of abandonment legally. Now, you can not Rx more than 3 days of a narcotic and have to go on government sites to monitor patients to make sure they have not had any other Rx’s. Your points of alternative are valid and do work well. THC may be a good middle ground for some - non- addictive and some pain pathways, but not great guidance of how to use.

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Contrary to popular opinion, opioids are not universally addicting. About 25% on the high end. Fortunately, I have never become addicted to anything but nicotine and coffee. I had no trouble giving up smoking when I thought it had become ridiculously expensive at 50 cents a pack.
Never tried to give up coffee because I always considered it healthy for me.

Shocking confession:
At my age, I would happily smoke an opium pipe now and then like Sherlock Holmes did if it were legal. It was portrayed frequently in black and white film noir.
“In urban areas of the United States, particularly on the West Coast, there were opium dens that mirrored the best to be found in China, with luxurious trappings and female attendants.”
Very interesting Wikipedia entry:Opium den - Wikipedia

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Since I have completed both degrees I think I am quite qualified to judge but in general MDs are completely ignorant on dental issues but the other way around is not true, most dentists are pretty knowledgeable on medical issues (but without the clinical experience of the internships that come with a medical degree). I did medicine first and dentistry after, dentistry was harder, much harder…

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We seem to have gone a little off topic here. Still interested to hear people’s views on whether rapamycin inhibits muscle healing post injury…

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Not a doctor of course, but there is a plethora of research showing rapamycin slowing down angiogenesis (and wound healing). Is a hamstring injury recovery at all mediated by this pathway?

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Based on my experience recovering from umbilical hernia surgery, I would say yes, rapamycin does slow down the wound healing process. Been off it for awhile now and healing rate seems to be improving. Only silver lining in the cloud of delayed healing: some evidence that my Indian Sirolimus is the real thing.

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Just anecdotal but I had a cycling accident (again) 2 days after I took 4mg and wound healing (road rash and a cut requiring a few stitches) was really good, much faster than usual. I did get herpes labialis 2 abd a half weeks after that …

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Recent comments on this generally topic by Matt Kaeberlein:

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Even MK is speculating…so much we have yet to learn.

Based on my recent experience with recovering from umbilical hernia surgery, I would say that rapamycin does slow wound healing.

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Did you discontinue Rapa at all for your surgery?

Are you talking about just the incision or more broadly?