Bezesk
#18
I would have preferred buying a few grams from a reliable Chinese supplier and then having it third-party tested. The drug has high oral bioavailability.
So I’m very interested in all this, particularly a lithium-rapa combo since my studies show the main issue with rapa and cancer is ubiquination mediated by GSK-3 preventing mtor inhibition in cancer.
However, I’m very wary of MEK inhibitors as I started taking dihydromyricetin high dose (2 grams) in January of this year and it seemed to cause profound skin aging effects that are only recently starting to go away.
I took dihydromyricetin years ago and didn’t have these problems.
I’m still wary of lithium until more research.
But all these molecules have long history of supplementation so like with many things - it appears the dose makes the poison. 
1 Like
José
#24
My thoughts are like take rapamycin for longevity weekly
Starting 2g a week of trametinib to start
Are you taking 2g a day for treatment for?
Livin
#25
Do not take trametinib for longevity purposes. I worked on synthetic lethal chemo combinations in cancer at a startup for years. We tested this compound and it is not a good idea. The Erk pathway is very important for most epithelial cells. Stick to low risk acarbose and rapamycin combinations and do not consider trametinib. If you have melanoma or another type of solid tumor type then you could consider trametinib. Just trying to prevent you from causing long term damage.
14 Likes
@Livin @Vlasko Thanks for sharing this vital piece of information. You may have just saved a few people from making a dangerous mistake.
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José
#28
Livin, if you have reference to published paper please provide.
Livin
#29
The problem is most targeted protein kinase inhibitor clinical trials are done in patients that failed first line chemo so this is a drug population that can’t be studied long term since they often have less than a year to live. I expect most long term side effects are not documented. The side effect profile does not look promising for a drug used for longevity purposes. The study of combination longevity effect also observed a significant reduction of fecundity so I hope you do not plan on having children. This is presumably also going to be combined with rapa which is also known to reduce fecundity. So I will restate that MEKi drugs all around are a bad class of drugs to consider for longevity based on my risk reward calculations.
7 Likes
Wow - really good information. Thanks for posting this. Its great to have people here who have some in-depth experience with some of these compounds and biochemistry.
5 Likes
Beginning to explore the possibility. Thanks for your posts.
1 Like
Chula
#32
Which drug are you talking about here the rapamycin or the Trimitilab (sp)?
Vlasko is talking about the Trametinib. I recommend you read this new thread on this drug: A Combination of Rapamycin and Trametinib Extended Maximum Lifespan by up to 35%
2 Likes
enature
#34
What do you mean by rapa is “also known to reduce fecundity?” A recent study shows that a weekly 5mg rapa administration extends child-bearing age for women by decreasing the aging of their ovaries.
1 Like
José
#35
In males, sperm count is reduced for starters.
During dosing (similar to caloric restriction), and reversed to the best of our knowledge after pausing. Details here: How Safe is Rapamycin (part 2)
1 Like
Powe
#38
How are you planning to determine dosing — amount and timing (daily, weekly etc)? When I started taking rapamycin I was able to look at human studies that correlated effects with doses and compared that to mouse and monkey studies. It looked to me as if many of these studies across species had roughly converged on similar amounts per pound of weight. And the choice of intermittent vs continuous was often the same too across these groups. I looked at the mouse study posted for Trametinib and rapamycin combinations. The amounts were implausible. Given the magnitude of the numbers they gave for rapamycin, they do not make sense. Maybe they provided the dose by the weight of the feed not the animals? If so, I have no idea how to translate this into dose/body weight for the Trametinib since I don’t know how much feed they gave each mouse. If the dose/body weight suggests a vastly smaller dose than given for cancer, as it does for rapamycin, then the risk of serious side effects may similarly be much less as well.
