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.
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.
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.
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.
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.
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?
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.
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?
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?
Tolerable CR while young and then rapamycin when older could be additive. Would sort of like to see that tried out .
Doing them both in the older age groups strikes me as redundant with rapamycin having the advantage.
This brings to mind the old joke: dieting might not make you live longer, but it sure feels that way. I like being healthy and in shape but I also enjoy food and not being cold (except for brief immersions) and if one must be miserable to live longer, I’ll have to take a pass.
Update: Today, After my 4th dose on saturday i have two pimples on my face. I heard of acne being a side effect and it’s been many years since I had more than the very infrequent pimple. I wonder if this is an indication I should lower my dose. I feel perfectly fine otherwise.
Acne like pimples, especially on parts of skin covered with hair, is a side effect. I get 1 on top of my scalp every time I overdose or have a shorter break. I would lower the dose.