Man, of all the side effects of Rapamycin, these two are the worst. I don’t know how I could ever live with these. I’m out. 
As for abdominal pain, Rapamycin can cause it as can Metformin. That’s the problem when you’re juggling too many balls at once. It’s hard to attribute the side effect with the right cause.
The side effects and magnitude are most likely dose dependent and may be also due to daily vs weekly intake differences. For example, impaired kidney function, ~30% raise in the serum creatinine concentrations occurred in those taking 2-5 mg sirolimus daily.
It is important to increase your water intake when on rapamycin. It will trigger my gout if I don’t drink more water. I’m hoping that it will decrease my uric acid level in my next test for uric acid in 6 weeks time.
Hey, you said that you were never going back to Kansas! Oz forever.
My comment (about visceral fat) was more as a possible explanation for weight loss which he mentioned it as a negative side effect (which it wouldn’t be for a lot of people). But visceral fat isn’t always visible. See here:
https://www.webmd.com/diet/what-is-visceral-fat
I’m actually thin (and wouldn’t want to lose weight when I start rapamycin) but I’ll do a DexaScan before and after rapamycin to measure visceral fat (which I could have) and bone density - both of which could improve with rapamycin.
And in regards to your mention of balls and his complaint about lowered libido - there’s this about Metformin and Testosterone (since he doubled his Metformin dose that could be a factor in both weight loss and lowered Testosterone).
https://mikesbalance.com/metformin-and-testosterone/
Not sure how authoritative that website is but he’s a health professional and he’s got a great first name (but he’s Russian so he probably drinks a lot )
P.S. I’m also hoping that rapamycin increases the strength of my eyelid because with more positive attitude and sense of humor, I’m going to have to do a lot of winking!
HRV went down substantionally a month after starting dosing that was ramped up from 2 mg to 6 mg. Deep sleep dropped, all my oura ring measurements dropped. Respiratory rate increased. Had trouble breathing. Felt heaviness in my lungs. Woke up dehydrated and dry mouth for first time. after 10 days from taking last dose my Reddiness score on Oura ring was back over 90% and my overall Sleep score was excellent again. My deep sleep has continued to be lower than it was but I think it will return. It went from 1 1/2 hour deep to 45-55 min deep over the past month. After taking some time off I will give it another go at a 2 mg dose.
I was in PEARL Study at 8mg 1X a week. I had no issues. I have started back up on my own 3 months later at 2mg. This is week 3. Week one I had no side effects. Week 2 I felt tired and achy the next day. Week three my BP shot up to 156/80 4 hrs after dosing. I felt horrible. That night I started flu like symptoms, or body aches, head ache. The day after I was very sick but BP returned to 108/50 and normal EKG. Day three I was back to normal. I don’t know what to think. Was I just sick? I also have Rheumatoid Arthritis that I have controlled with LDN 4.5mg. For 6 years. I don’t know what to do. Should I discontinue Sirolimus.I have asked my prescriber and was told high BP was not a symptom.
I don’t know if you saw my post below, but your experience seems a lot like mine. I did PEARL with no issues at all. Now I am going through AgelessRX for my Sirolimus. They started me at 2 mg. I am experiencing fatigue/ flu like symptoms and an alarming BP surge that did subside after 12 hours. I gave up three days this week to being sick. Not sure if it was Sirolimus or the flu. I’m very reluctant to dose up again next week.
Of course, everyone has individual responses to rapamycin, but in over two years of taking relatively high doses of rapamycin, I have had nothing but good results apart from diarrhea when I take too large a dose, no fatigue, no colds flu, or other illnesses.
Thinking mechanistically anything that encourages mitophagy has the potential to cause a temporary fatigue whilst the body’s energy generation is reduced prior to the creation of new mitochondria.
Also if energy levels are increased I would expect BP and HR to be increased temporarily. I think that is what happened to cause my BP to increase. I have ended up with a higher Stroke Volume, but lower mean arterial pressure.
I get diarrhea if I take too much of any medication. Lol.
New to taking rapamycin. Started 1 mg a week, then took 2 mg and had 1 small canker, went away quickly. Then next week dosed at 4 mg and had several cankers leading me to delay dose at day 7. Took 3mg at day 9 and had had multiple painful cankers that affected my ability to eat and brush my teeh. Using Sensodyne, no SLS. Used OTC Kanka and had Rx for topical clobetasol gel (steroid) to apply with a gauze pad. I am now at 14 days and my cankers are finally gone. Not sure what I will try next. 2 mg a week? Frustrated by my bad cankers. For reference I am 125 lbs and 59 years old.
Thats a pretty low weight - the average weight for males here is probably around 160 to 190lbs.
You may want to keep it lower for longer (e.g. 1mg or 2mg for a month or two) and only slowly go up by 1mg every few weeks. What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?
I agree but also try Lysine and vitamin C. I am just about done with Robbin’s book about copper and Iron and it turns out you really should use like Acerola Cherry vitamin C. Something derived from plants.
Just an idea, take what you want and leave the rest.
I am having fatigue as well does this tend to ease?
@pmoskie I’m about 120 lbs and have pre-existing autoimmune disease. I’m experimenting with Rapa to see if it can act as a immunomodulator so I can stop methotrexate and escape its unpleasant side effects. My first round (over a year ago) started with 2 mg, the following week 4 mg, then 6 mg and my side effects were extreme thirst, and a strange wired feeling/nervous energy, increased insomnia. I took 6 mg for a couple of months and did a washout as I left for a long trip and it was a convenient time to do so.
A few months later I restarted at 1 mg per day x 5 days a week - based on some comments in this forum linked to papers re a dosage protocol being studied for autoimmune disease. I immediately got canker sores! None at the higher weekly doses btw. I used a strong salt water rinse and they subsided.
I took another long break to trial colchicine (which is contraindicated with rapa) for my autoimmune disease. Trial over, restarted rapa 5 weeks ago: 2 mg, 3 mg, and now 4 mg per week which I’ll remain at. No canker sores, no unpleasant side effects, but no improvements either. It’s all a WAG and there are no answers, not yet anyway. 
I stop most supplements for at least a month when I try new protocols and track my BP, watch my Oura feedback, note my energy levels and joint pain to not muddy the waters of the rapa experience. I’m about to try GlyNac and will report on that in a few months after blood work. Good luck!
I was experiencing an intensely itchy rash on the tops of both shoulders and on my right knee, and occasionally on the back of my neck, from the sirolimus dosed at anywhere between 2-6 mg/wk - it did not matter. This went on for my first 2.5 months of use. After a lot of research and reading about sirolimus inflammatory syndrome and pruitis sometimes experienced by transplant patients taking daily sirolimus, I got the impression that could be cytokine imbalance, which triggered me to think about a supplement I’d been taking for the last year called Cytokine Suppress by Life Extension. It contains EGCG and Vitexin/Isovitexin. I stopped that supplement a week ago, the rash has disappeared and not returned. If anyone else is experiencing a rash and takes those things, try eliminating them and see if that helps.
I think it’s possible that the pleiotropic benefits of several drugs, metformin, acarbose, SGLT2-inhibitors, GLP-1 agonists, could have important effects on the microbiome.
I spoke too soon and have to take it back about that supplement together with sirolimus triggering my rash. I’ve been off the supplement for a week and a half and though my symptoms initially subsided, my itchy shoulder and knee rash came back last night and today, 5 days after taking my weekly sirolimus dosage. Last time, it also got worse the day after my sirolimus dose. It may have to do with a cytokine imbalance triggered by the changing levels of sirolimus, but it wasn’t that supplement.
There is some literature out there about sirolimus-induced pruritis and how it’s associated with increased thymus and activation-regulated chemokine (TARC) levels and eosinophils, and other literature about how sirolimus affects keratinocytes (skin cells that are part of the immune system), which produces TARC. In some instances, topical corticosteroids and antihistimates (H1 and H2 blockers) were effective. A topical corticosteroid didn’t do it for me. I took a claritin and famotidine earlier today (as I also did a week and a half ago, with zyrtec and melatonin at night) and think it might feel a bit better. I will have to experiment.