To be frank I’m not sure how objective the personal observation of a ‘reduction of the number of wrinkles’ would be. And would it be more objective than changes in energy levels that members have described?
I don’t have any wrinkles that I know of, but I have not observed any changes in the quality of my skin since taking Rapamycin. (And after I’ve had to take steroids for years that seem to have thinned out my skin, I would certainly have been happy with observable skin improvements 
). I did observe an increase in energy levels.
4 mg is too much to start with imho. I would start with just 1mg. Give it a try for 3-4 mo.
I have two points to contribute to this discussions.
I’ve tried the CRON diet for a year (caloric restriction with optimal nutrition) as outlined by Roy Walford and his daughter years ago. Had individual meals premade with the correct nutrients and calorie count, so I knew I was doing CRON and not cheating. It was hard! You’re always hungry. You’re thin and cold all the time. You lose muscle mass. Its not a pleasant experience and I don’t know anyone (of many that tried) who managed to maintain the diet.
In other words, the side effects of CRON are extremely high, and rarely acceptable to people (true CRON (e.g. reducing calories by 30% or 40% from normal), and not just skipping the odd pizza).
Moreover, we know now that Rapamycin is not a caloric restriction mimetic. They impact some of the same pathways, but they are like an overlapping Venn diagram. See here: Even with calorie restriction, rapamycin slows muscle aging
I’ve been on rapamycin for three years. Its not hard. Minimal side effects. I’m not hungry all the time. I’m not cold all the time. My mood is much better than it ever was on CRON. The side effect profile for Rapamycin vs. CR is 95% better in my experience.
While the research shows now that caloric restriction likely won’t extend lifespans in mammals if started after childhood, Rapamycin seems more likely to.
From my experience with both - Rapamycin is the hands down winner.
Your mileage may vary.
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Most people have no side effects. Those that do - typically just get temporary mouth sores that go away without treatment after a few days, and small rashes that also go away.
To minimize risk of side effects I would start at 1mg, slowly increase by 1mg/week until you get to your target dose. In my experience that minimized my side effects (one mouth sore in the first year of using rapamycin).
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Thanks for your opinions and suggestions!
Have you seen this page: Side Effects of Rapamycin (part 2)
And this page: Anti-aging Benefits of Rapamycin, Personal Experiences (part 2)
and this: What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?
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I believe rapamycin and time restricted feeding has allow me to reach stasis as far as weight is concerned. My weight has remained stable at my target weight for several months now. I follow a mainly South Beach diet which is a little higher in carbs and little less fat than a keto diet. Mainly I eat what I want and occasionally cheat. The only reason I eat two meals a day is that it is just too uncomfortable for me to try and get my day’s calories in one meal.
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I have been taking Rapamycin (purchased from AllDayChemist) for the last 2-1/2 years. I started with 6 mg/week and went up to 10mg/week (one day a week). For several months, I tried 20mg/2 weeks.
During the first year I had canker sores three times. They healed in 2 or 3 days. Other than the canker sores, I have had no other side effects. I also don’t “feel” any different than I did before taking rapamycin. i usually take the rapamycin 30 minutes after eating a small or medium grapefruit.
So from my experience, there is no reason to have side effect fear. I do keep some anti-biotic treatments in the refrigerator ready to use if ever needed.
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I started taking rapamycin a few weeks ago with 6 mg / week from the start. So far no side effects except my post meal glucose levels have been much higher but this only last for a day or two (I am not diabetic but I like to keep track of blood sugar levels to keep them low and stable for general health). The corrective I will take for this is to just eat less carby foods on the day I take Rapa and the day after. Otherwise it looks like my fasting glucose is actually a bit lower.
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I remember there are some rodent studies wherein Rapa-administration in females resulted in higher serum levels of Rapa than in males. I have not been able to find any suggestion with this regard: but is this gender difference apparent in humans also?
Admittedly I’m surprised when I see that other members don’t experience side-effects. Unfortunately I can’t measure blood serum levels of Rapamycin where I live, but the side-effects I have experienced are not insignificant. I should say that whereas most members of this forum apparently don’t have side-effects, on another forum more members expressed having experienced side-effects. I’d gladly share pictures with the admin of the rash that comes back each time I dose with Rapa, if it may be informative. (The rash disappears roughly 1,5 weeks after dosing Rapamycin).
The past two months I have experienced an additional side-effect that nearly made me ask for a mammogram, until I ran into this study: https://www.medicaljournals.se/acta/content/html/10.2340/00015555-1889
I don’t want to hijack this thread, so I will keep it at that.
I don’t take any other drugs, besides Empagliflozin 10mg each day.
As said, I may perhaps have about half the weight of some males here, so I’m guessing that may also make me more prone to experience side-effects.
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I am suspicious of those experiencing no side effects unless they are on very low doses or maybe they are experiencing very low absorption.
Mikhail V. Blagosklonny, MD/PhD. Professor of Oncology
Has expressed the opinion that you should take the highest dosage without experiencing negative side effects. Also, animal studies have suggested that the higher the dose the better.
It has also always been suspicious to me that doctors prescribe medications without taking body weight into consideration.
It would seem to me that you should back off of your dosage until you quit experiencing side effects.
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It makes sense. That was exactly what I did: backed off my dose till I reached the stage with no side effects. Definition of high dose is very individual.
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Exactly this has been my motivation to not want to dose too low. As well as Blagosklonny’s past comments that a higher dose may possibly make it past the blood-brain barrier. So I started dosing once per 2.5-3 weeks instead, without wanting to compromise on the amount of Rapa I dose with.
I think you are right that it may be wiser to decrease my dose. On the other hand, based on those studies and the fact that we are taking significantly lower doses: I have my doubts that low doses are really effective.
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I think that it’s becoming fairly clear that females are more sensitive to the effects of rapamycin, both good and bad. This is probably due to lower mTOR levels and activity in females.
Also, recall that in the very high dose study by Kaeberlein, it was the males that thrived but the females got hematologic cancers. They’re clearly not as tolerant to the drug as are males.
With males it does seem like the more the better and even adding on other drugs like acarbose helps the males only. This could be because the females have already gotten a max effect from the rapa and other meds aren’t able to add to it.
It’s not true that low doses have no effect. Several studies show benefits to low dosing especially on the immune system.
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All of what you say is true, but I don’t believe that they see the same differential effect of rapamycin in female humans, specifically in transplant patients. While ultimately what they test for is blood/sirolimus levels (off the top of my head I think the target is 15ng/ML to 25ng/ML) and they probably adjust the doses individually to meet that target (in their case, via daily dosing), but I haven’t heard of the big difference in dose/responses that we see in mice for females translating to humans. Have you?
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So hard to say because we don’t have the human longevity studies and the transplant patients are such outliers due to their overall health and dosing.
Here’s one interesting example though. In concentration camps during the holocaust obviously people were subjected to extreme calorie restriction to the point of starvation. I would say that this amounted to very significant mTOR inhibition.
The female holocaust survivors showed no survivor advantages in terms of lifespan, but the male survivors did show a significant lifespan advantage.
In other words, the extreme mTOR inhibition from years of deprivation gave a significant advantage to males where, once again, the more inhibition the better.
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Its more similar to eating less protein , than just eating less total calories.
When they reduced BCAA (animal protein aminos) in male mice the life extension was very comparable to rapamycin.
CR is somewhat different gene expression pattern it brings in other factors like AMPK , different pattern.
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Thank you for the insightful post with regard to the potential effects of Rapamycin in females.
I had my IGF-1 blood levels measured prior to starting Rapamycin, and they were rather low. Perhaps given my lower weight and the fact I’ve tried to stay lowish in protein per Longo’s research - at least until I reach an older age.
If one may have been practising mild CR already, could Rapamycin be ‘additive’ and would the combination of the two thus potentially result in even lower mTOR activity?
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I was aware of the studies showing that holocaust survivors experienced an increase in lifespan - but I had no clue that this advantage was only seen in males. Do we have other comparable research that shows a similar trend?
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