One of the great aspects of this forum is that most of the members understand the importance of dosing Rapamycin. Some new members may not yet know about dosing. The importance of dose extends to many of the other longevity oriented interventions many of us are interested in.
Taking too little or too much of something may not provide the expected results. It’s almost always best to start experimenting with lower doses and work up to the recommended dose over time. To find proper dose information it often requires reading a lot of clinical papers and asking a lot of questions.
There are 2 basic dosing relationships.
Dose Dependent Response
This type of response is when something provides an ever-increasing response, the more you use the bigger the effect until the effect stops increasing. Conversely if you don’t use enough there may be no benefit at all. This is often based on the ability of your system to utilize the dose. Think Vitamin C where you can take as much as you want but the body’s ability to absorb it plateaus and your body will excrete the excess. This can apply to certain drugs, peptides and supplements.
Hormetic Response
Hormesis is defined as a dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition. When you take too much, the benefit goes away and can become a negative effect in the same area. Think over training, too much training does not allow the body time to recover, and performance is lost. This can apply to certain drugs, peptides, and supplements.
This aspect of drugs, supplements, and food goes along with dose. The things we consume and absorb don’t stay with us forever, they decrease in content and effectiveness over time. Some things decrease rapidly, some very slowly.
Fast half life
For example, the half life of BPC-157 (one of the healing peptides) is about 2 hours. This means if you take 1mg, in 2 hours there will be 0.5mg left in your system, in another 2 hours it will be down to 0.25mg and so on until it’s effectively all gone in less than 8 hours.
Slow half life
Rapamycin (the most potent longevity drug to date) has a longer half life of approximately 60hours (can vary by individual 50 to 80 hours), about 3 and half days. If you take 1mg, in 3 days you will have 0.5mg in your system in 6 days you would have dropped to 0.25mg and so on until it’s all gone in about 15 days.
When deciding how much and how often to take any substance, understanding dose and half life is very important. For typical day to day things like food and the typical supplement, it’s not worth considering.
Something that is worth considering is the LD50 of any compound you take.
LD50 is a term used in understanding the potential toxic effect of a substance.
LD50 means “Lethal Dose that causes 50% of the test subjects to die”
This is something I look at for everything I personally experiment with. I want to know if something has any toxic potential so I can evaluate the risk/benefit potential. And dose.
Even if something can be lethal at high doses, it does not mean there is no benefit at therapeutic doses.
Understanding this aspect of drugs and even supplements is important. For example, there is an LD50 for Tylenol (paracetamol/acetaminophen) but that doesn’t stop us from using it for headaches and pain. The LD50 for humans is around 12gm, which would be 24 x 500mg pills, an extremely high dose, while 1 or 2 pills can be quite beneficial, up to about 8 x 500mg = 4,000mg or 4gm per day is considered the maximum safe dose per day.
This is a great thread - thanks for posting this information.
One other thing related to these topics is the relationship of dose level to side effect profile, specifically with regard to rapamycin.
I see many journalists who have written stories on rapamycin saying it has this or that terrible side effect, without noting the dose used, or the frequency of dose, in the studies that are associated with that given side effect. Rapamycin has many undesirable side effects when dosed very high levels such as when used in cancer studies (up to 90mg/day). One study noted:
The optimal cancer-fighting dose for those taking sirolimus was about 90 mg per week. At doses above 45 mg, however, the drug caused serious gastrointestinal problems, such as nausea and diarrhea, so patients taking sirolimus alone switched to 45 mg twice a week.
Of course, in most people using rapamycin for longevity we dose only 4mg to 8mg once per week, so most of us never see these types of side effects.
I had no idea it was 15 days to get to zero rapa in blood. No wonder I have to use a 2 week cycle to avoid issues (essentially just feeling tired). Even then I take an extra week every 4 weeks to make sure. Thanks. I’m thinking more and more about @John_Hemming use of a 3 week cycle.
I was always working on the basis of a half life between 60 and 65 hours.
Can it be up to 80 hours? (As mentioned above)
By the same token can it be as little as 40 hours?
That is a good question. I have seen wide variances in published articles. Problem I see from those articles is the species used. Some use mice, rats, dogs, etc. Some use human based half life data.
Since we are primarily interested in the human related half-life here is some info, indicating 57 to 63 hours.
I’d ask, how long will it be before we know the answer to that one, “what is the correct dose”
I’m going out on a limb here and say it depends, related to “correct” dose part of that question.
As far as what understanding the concepts of dose, half life and LD50 mean, those are good scientific concepts to understand for anyone who is self experimenting with various drugs, supplements, peptides, etc.
For me, it helps with pushing the limits of what I’m willing to risk at this point in my life.
Since I’m not going to wait 10 or 20 years to see a study with the correct dose, time is ticking by and I don’t want to wait until I’m 80 or 90 to start some of these interventions.
I think the best course of action is to take a Rapamycin blood test the day before you plan on taking a 2nd dosage. Assuming you are not daily dosing. Example, if you test after 6 days and your blood levels are still high, you either need to adjust dosing or timing.
In another thread, I saw multiple options posted a long time ago for purchasing a rapa blood test. Can you simplify this for me and share what a good cost effective option is … TY!
I don’t understand that myself. I have tended to work in the hard science, tech, mathematics and accounting environment (ignoring politics and music for the moment). I cannot understand why when you have a drug that has a half life of around half a week that people take it weekly if they think mTOR (which it inhibits) has any benefit at all.
I see Rapamycin as something that encourages autophagy. That is not something to do all the time.
