There is a YouTube discussion with Brian Kennedy (NSU, formerly head of the Buck Inst.), where he talks about rapamycin and MTOR. MTOR is definitely something we want turned on some of the time for growth and repair, its just that when its over-active all the time that it causes problems. Thus - the pulsed dosing of rapamycin that has been adopted for anti-aging.
5 Likes
Right, but even organ transplant patients on continuous higher doses don’t have profound neurological issues, at least as far as I know.
2 Likes
True - but even in transplant patients I don’t think the doses are not so high to completely shut down MTORC1 all the time, and ultimately mTORC2 most of the time.
I think the transplant-focused doctors are trying to find balance between a high enough rapamycin dose so as to help lower the immune system just enough so that the organ is not rejected, but not so low as to make the person too susceptible to infections, etc.
Thus - even transplant patients are not going to have MTOR inhibited all the time. So, while I still need to study the paper, I’m not sure its relevant to most of us using rapamycin - especially on the pulsed weekly or every two weeks type of dosing protocol.
2 Likes
I have already posted about having flatulence and mild diarrhea, but now I know a side effect I didn’t report: My fingernails and toenails have become thinner and more fragile. I attributed it to the fact that I have been spending more time in the spa at the gym I belong to.
Adverse side effects I have experienced while taking Rapamycin at a high dose, 20mg, with grapefruit juice: " This makes the drug reach higher levels in the bloodstream, two to four times the levels seen without a juice boost" This was an oral liquid dose.
Rapamycin adverse side effects I knew about: “Many patients in the study did report side effects. More than half experienced elevated blood sugar levels, diarrhea, low white blood cell counts or fatigue.” My diarrhea lasts 3 to 5 days after a large dose. Not to be too graphic but it manifests in loose, but not liquid stools. This is unfortunately accompanied by “wet farts” that leave tracks in my shorts.
Side effects I didn’t know about: "Duggan, more fortunate than most, has had milder side effects, including fragile toe and fingernails and curly hair. “I now have very curly hair,” she said, “seriously curly. I have to adjust to it.”
Grapefruit juice boosts drugs anti-cancer effects - UChicago Medicine.
3 Likes
It’s actually quite promising that you’re taking an effective dose of 60mg and still only having mild symptoms. I think most of us would take the flatulence for 7 more healthy years!
1 Like
I may not be getting a higher dose than 20mg. I just use ruby red grapefruit juice that I like from my local grocery store. Some grapefruit juice has no effect. So, since I take Rapamycin on an empty stomach I could actually be getting a lower peak dose than I would get if I took it on with a high-fat meal. The dose I am taking is much higher than is needed for life extension and I certainly would not recommend it to younger people. I am trying to take a high peak pulse dose because only small amounts of Rapamycin cross the blood-brain barrier and I am taking the higher dose for the possible effects it has on delaying dementia and/or Altzheimers. I also, IMHO, think that the short high dose probably has less effect on the immune system than a prolonged dose of Rapamycin taken with a high-fat meal.
1 Like
I haven’t gotten a cold since pre-COVID and have a pretty bad one now. Granted someone in my home has one too. Anyone find they get colds more easily? And once they have a cold, more prone to ear infections? Sinus infections? Etc. I try not to obsess over things, but trying to attribute anything out of the ordinary to Rapamycin.
Haven’t had a cold or flu in past 4 or 5 years, been on rapamycin for 2.5 years. So i don’t think any connections…
5 Likes
Honestly I don’t think you should expect to see any effects, positive or negative, after 3 weeks at 3mg.
FWIW my wife and two daughters all had bad colds last month. Touch wood I’ve been fine.
1 Like
So the numbness and whatnot is back and have had more episodes this week. I did 3mg again on Monday. So my third dose. I had Lyme disease several years ago and have had some weird neuropathy come and go since. I wonder if the Rapamycin is triggering something there. I did some reading/research but don’t see a lot of Lyme - > Rapamycin other than a 1950’s study about positive effects on arthritis in Mice. I am having my annual physical next week and going to talk to my Dr. Not sure if I should stop Rapamycin altogether or lower dose or press on. Too much caffeine can trigger similar symptoms so wondering if Rapamycin’s stimulating effect is to blame. Quite the puzzle.
1 Like
Suspect it’s just the nocebo effect
2 Likes
Don’t think nocebo. Numbness and pain in my leg today is pretty severe. Feels like gout. Tongue numb. There isn’t a ton of research on autoimmune interactions with Rapamycin, but logically it makes sense. This study Low Dose Rapamycin Exacerbates Autoimmune Experimental Uveitis - PMC. Mentions you have to be careful with the doses if there is this specific autoimmune.
4 Likes
Actually after much reading and self analysis I think the side effects are the Metformin and not Rapamycin. I might have an underlying Kidney issue causing them. Stopping it immediately. Again, seeing Dr this week.
4 Likes
I get skin infections on my shins after taking rapamycin. I’m in healthcare so I know what infections look like. They appear to be penicillin and clindamycin resistant. Doxycycline or azithromycin treat them well. I also usually have a little bit of tinea versicolor on my chest. The rapa eliminates it almost over night. By the end of my two week interval I can see it returning. Otherwise no other side effects.
3 Likes
Sometimes there are benefits you are experiencing but are overlooking when taking rapamycin.
After replying to the wound healing question, I was thinking if there were other negative or positive benefits that I have experienced since starting rapamycin. I am ~81 yrs old, so getting a late start with rapamycin but, I have been taking various health food supplements since my mid-twenties, including some that later were found to have life extension or healthspan benefits, so all is not lost. I have been taking rapamycin at various doses for 5+ months.
Because I have been going to the gym on and off throughout my life and was an active jogger and tennis player for many years, I am in pretty good shape for my age. That is why I probably
overlooked some possible positive benefits.
Number one: I was pretty much at my desired weight goal of 175 lbs. (I am 6’2’) when I started rapamycin but had to watch what I ate even though I practice time-restricted eating. I have noticed lately that I am almost never hungry and have to force myself to eat enough to keep my weight from sinking too low. Maybe this is because of another side effect from rapamycin or some variant of Covid that I didn’t know I had. Anyway, food just doesn’t taste as good to me as it used to.
Number two: (and most important to me) A dramatic decrease in the number of new actinic keratosis on my face and scalp. I live in the desert and was chronically exposed to excessive sunlight in the days before SPF was a thing. We thought suntan lotion was a little iodine mixed with baby oil. So, I have what my dermatologist describes as chronic keratosis. This means even if I am never exposed to UV again I will still have actinic keratosis that has to be taken care of with chemicals and/or cryosurgery. It just occurred to me that I missed my quarterly appointment and it doesn’t look like I have any new ones that need taking care of.
I would really like to know if anyone else has noticed an effect on their appetite or skin since taking rapamycin.
7 Likes
I started at 2mg., with 8 oz. grapefruit juice the night before and eight oz. of grapefruit juice the morning of taking rapamycin, and had no side effects. Each week I increasedthe dose by 2mg. until the third week. At a 6mg. dose with grapefruit juice, after 12 hrs, I had sore gums. I took one amoxicillin and the soreness stopped quickly. At thirty hours I was fatigued, had soreness in the shoulders and arms, and music welled up loudly in my ears, all lasting for an hour or two then went away. This could only be attributed to the rapamycin as everything else in my life and health was totally routine. If long lasting it would have been horrible, but was very short in duration. The next week, I reduced my dosage back to 5mg. with grapefruit juice, and never had a symptom good or bad again, taking bi-weekly for a year.
5 Likes
Also my cholesterol numbers have gone up some, to which I take 5mg. of statin three times a week, which is minimal.
1 Like
Blagosklonny suggest increasing dose weekly until experiencing mouth soreness and then reducing the dose slightly. This is the method to determine what is considered your optimal dose. It’s also suggested that a minimal dose of antibiotic will cure the mouth soreness, and did for me. He also suggest taking a week off after three.
3 Likes
Did Blagosklonny comment on the mechanism of the rapamycin-induced mouth/gum soreness, and/or why an antibiotic would alleviate it? This is the first time I’ve heard of this potential side effect of rapamycin.
The washout period seems to make more sense than Antibiotics which I believe are Counterproductive to the fact they disrupt the microbiome and one of the positive effects of Rapa is on the gut health.
5 Likes