Make your arguments for Rapamycin dosed Once Weekly vs. Once Every Two Weeks

[RapamycinCurious]

Hi,

@desertshores

Yes, I am well aware of the more is better theory. This may be true for rats, mice, fruit flies, etc, but of course everybody knows that these studies don’t always translate to humans.

Humans have more genes in common with cats and dogs, than rats and mice.

Two things here. First, that’s narrowly true of cats but not dogs: humans share 90% of genes in common with cats, but 85% with rodents and 84% with dogs. Additionally, domestic catas have an exceptionally high frequency of disease-causing SNPs,

substantially higher than previous studies in other mammals, such as, cow [38], dog [39], rat [40–42], sheep [43, 44], pig [45], and horse [46]. Even rhesus macaques, with twice as many variants as human, do not approach the same levels of cat SNV variation [47, 48]."
A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism

This relates to another misunderstanding you appear to have below.

Additionally, whatever other merits cats and dogs may have as experimental models, we don’t have any rapa lifespan studies in either species (yet). Absent that information, the cat and dog data are only of interest for hints of conservation, regardless of how closely-related they are.

@desertshores

My own blood work over the course of ~15 months indicates that the high doses I have been taking are probably detrimental or at least not optimal. Many other forum members have reported worsening blood test numbers such as ferritin, MCW, etc. while taking rapamycin.

The fact that you had more side-effects on higher doses does not mean that lower doses are more or equally effective. Depressing as it may be to contemplate, it may be that the doses required to meaningfully affect human aging are not achievable without unacceptable side-effects. Certainly translating the rodent dose-response studies raises that concern.

@desertshores

So no, I absolutely believe that there is an optimum dose and/or frequency for taking rapamycin.

By definition there is an optimum dose and/or frequency for taking rapamycin. The question is how high that dose is and if we are even in the ballpark.

@desertshores

This study of cats being treated for hypertrophic cardiomyopathy indicates the best dose is not the highest dose.

Something you may not realize is that hypertrophic cardiomyopathy is not the kind of cardiomyopathy that happens to some degree in all humans as a result of aging processes including blood pressure and cardiac amyloid, but is a genetic disease that is common in cats but rare in humans. It makes sense that a genetic disease of heart muscle overgrowth could be treated with a drug that suppresses a growth pathway, but that doesn’t necessarily tell us much about aging in humans unless they are unlucky enough to be genetically susceptible to the disease.

@desertshores

I think the anecdotal reporting from forum members is beginning to give us a clue that higher doses are not necessarily more beneficial.

Aside from side-effects, which may or may not tell us anything about efficacy, what would you point to? Also remember that Joan Mannick says that nearly every person on placebo in her trials was subjectively certain he or she was on an anti-aging drug …

[Phil_Van_Treuren]

@RapamycinCurious

nearly every person on placebo in her trials was subjectively certain he or she was on an anti-aging drug …

This forum is full of great information, but it’s also full of people who are imagining lots of “miraculous” effects from a few rapamycin doses (both in themselves and their dogs). I’m at 10mg rapamycin per week and haven’t seen any positive (or negative) effects at all.

[David]

I like the discussion, data presented and arguments for what makes sense on what dosing approach to use. All that being said, this is an evolving process that is very common in medicine. Hopeful animal data, long term human data probably needing many years to collaborate and in the mean time a discussion of balancing risks and benefits. Our safety data seems to be pretty good other than knowing what taking Rapamycin may do for extended periods of time beyond our current data set. (more applicable for the 20 year olds taking Rapa)

I have made this argument previously on this site, but I feel for myself, I need to see a positive for why I would take on the risk of an unknown. The risk of doing nothing is known, so not unreasonable for the argument of doing some approach even without a noted positive change. For now, I take Rapamycin for its Healthspan value(decrease of joint and muscle inflammation) and hopeful for its longevity value.

Doseage adjustment is awkward at best:

• Feeling sick, mouth sore, bad labs = then wash out or decrease the dose.
• Feeling good and stable labs = keep the same dose.
• Not feeling as good as previous, bored with progress, wanting to get best optimal dose and normal labs - increase dose and or interval change.

@RapamycinCurious - has made some good points that none of our current approaches and or reasoning may have anything to do with optimal longevity dosing = best longevity dose could be with poor looking labs and side effects.

I do 3 - 7 mg / weekly without GFJ, trying night time dosing to enhance fasting mTOR effect and reading daily on what better options or reasoning is out there

[desertshores]

@RapamycinCurious

Aside from side-effects, which may or may not tell us anything about efficacy, what would you point to?

What proof do you have that rapamycin has any efficacy? Other than side effects I have seen no positive effects on blood work, than Agetron’s miraculously positive benefits.
I you put “ferritin” into the question box you will see the forum members that are experiencing below or significantly low iron levels after taking rapamycin. Maybe this is why some forum members experience tiredness after taking rapamycin. It certainly is not good long-term, unless you think anemia is a good thing.
I will continue to take rapamycin in the future but that is based on some faith in animal studies, not because there is any proof it does anything in higher primates.

Just as an aside: Recent pictures and interviews with Dr. Allen Green don’t seem to indicate that it is having any significant observational benefits. He does in fact seem old and frail to me. This is not a criticism of Dr. Green, it is just a subjective observation.

[Agetron]

I would tend to agree that a couple doses doesn’t make much of a difference. For me, it took 3 full months 90 days before I saw the 1st evidence of rapamycin doing something… which was at that point starting to remove the visceral fat about 15 pounds in weeks. Then the dysphagia…choking vanished. Then my strength started increasing 10 -15 pounds increases at gym every 3 months, skin started plumping up veins opened up.

Memory is the most amazing. I will be stuck on remembering a name or person… that I knew… . Pause… let my mind go blank… and bam… it appears… pretty amazing. Before Rapamycin, I would have to Google hints…to get it and then could move on.

On rapamycin 2 years and 8 months… I feel now the major miracles are done… lol. Just maintaining and keeping what I got back.

[anon16510610]

Interesting post here:

@MAC

Serum ferritin is a test that was formerly thought to be directly related to the amount of tissue ferritin, and thus, something that could be used to measure the amount of stored iron, which was believed to always be stored bound to ferritin. Today, modern research has shown that actually, serum ferritin levels are not related to tissue ferritin levels, and that iron is only stored bound to ferritin in tissues that produce ferritin, like the liver, and is stored in free molecule form in other tissues, like cardiac muscle, that do not produce ferritin. There is no required serum ferritin level; you do not need to be concerned about “depleting” it.

[desertshores]

That may be, but I have never had low ferritin levels without other blood markers that are associated with anemia also being low.

[anon16510610]

I don’t doubt you are correct.

Interesting though, that over the last two decades, my ferritin level has dropped steadily from 600 to 30 (last reading 80), and yet presumably related markers have been utterly trendless during that same time period. So, not necessarily correlated for high values of ferritin.

Couple years ago, I was sure ferritin was headed to zero. Doc did not evince concern, said there’s other stores.

[desertshores]

Thanks for the info. Unfortunately, I only have had a few ferritin tests to compare.

[DeStrider]

I think we can all say that the ITP results and other Rapamycin experiments have made a pretty good case for taking Rapamycin for health and longevity. The dog studies are also encouraging. So the question is how much do we take?

At 1-2 mg, some people experience side effects so Rapa has some effect at this point. However some do not. I would say this is too low of a dose for most.

3-5 mg seems to be a dose that packs a little more punch without too many side effects. For those preferring to play on the safe side, 5 mg and below seems to be pretty safe.

6-9 mg is where many of the longevity folk such as Dr. Attia and others are taking. A little bit more punch. This should be equivalent to 2-3 mg + GFJ.

10-20 mg seems to be the every two weeks schedule with a high peak at the beginning.

Then there are the true experimenters that do 20 mg+. They have shown us you can take this amount without too many bad side effects although this is where ankle swelling and some other side effects that are more major start cropping up.

Fortunately most side effects at any dose start reversing once dosing stops. The worst side effect is a bacterial infection which could be lethal if your immune system is too suppressed by Rapa. Please discontinue Rapa use if you have an infection or have surgery or major wound healing.

That seems to be a pretty good summary. Any modifications?

[RapamycinCurious]

@desertshores

What proof do you have that rapamycin has any efficacy? Other than side effects I have seen no positive effects on blood work, than Agetron’s miraculously positive benefits.
I you put “ferritin” into the question box you will see the forum members that are experiencing below or significantly low iron levels after taking rapamycin. Maybe this is why some forum members experience tiredness after taking rapamycin. It certainly is not good long-term, unless you think anemia is a good thing.
I will continue to take rapamycin in the future but that is based on some faith in animal studies, not because there is any proof it does anything in higher primates.

I think you misunderstand me. I am absolutely not sure that it will work in humans, and one of the reasons I’m in doubt is exactly because the animal studies that I agree are the core evidence around which everything else is just hints suggest that effective doses would be much higher than people are using now. As I said,

@RapamycinCurious

The fact that you had more side-effects on higher doses does not mean that lower doses are more or equally effective. Depressing as it may be to contemplate, it may be that the doses required to meaningfully affect human aging are not achievable without unacceptable side-effects. [Insert: This would include anemia]. Certainly translating the rodent dose-response studies raises that concern.

[John_Hemming]

Here’s my Iron results for the two times I have taken a relatively small dose of Rapamycin

Units Iron micromolar/l Ferritin mcg/L

24-Aug-22 LM Iron 15 Ferr 205

31-Aug-22 LM Iron 20 Ferr 145

Rapamycin 2mg 4th Sept

07-Sep-22 LM Iron 10 Ferr 175

12-Sep-22 MPS Iron 18.1 Ferr 157.9

21-Sep-22 MPS Iron (?) Ferr 165.7

13-Dec-22 NWP Iron 21.2 Ferr 170.5

06-Jan-23 NWP Iron 8.3 Ferr 123.2

Rapamycin 2mg 10th Jan

11-Jan-23 LM Iron 17 Ferr 150

19-Jan-23 NWP Iron 14.8 Ferr 152.6

25-Jan-23 NWP Iron 18.4 Ferr 147.6

I think the reason my iron was low on 6th Jan was heavy drinking over Xmas. I am currently planning on taking Rapamycin 4mg some time next week. However, that plan may change.

[idb]

Pretty sure I may be late to the party with this post. I apologize if it’s a duplicate.

Bryan Johnson has this posted on his Blueprint site:

---

"Every two weeks, I take 13 mg of gastro protected Rapamune. … To personalize dose and measure for safety and efficacy we’ve measured my Rapamycin blood levels 90 min, 4.1 days and 13 days post administration.

Blood Rapamycin levels:
90 min: 26.5 ng/mL
4.1 days: 2.5 ng/mL
13 days: not detected

Previously maintained a weekly Rapamycin dosing protocol of 6 mg. 24 hours post blood Rapamycin levels of the 6 mg dose were 3.2 ng/mL."

---

I’m still pondering either 6 mg weekly, or 12 mg every two weeks. Still a bit undecided, and from everything I’ve read, nobody really knows what is best so it might just be a case of pick one and run with it for a while and wait for hopefully more data to come in pointing in one direction or another.

[desertshores]

@idb

gastro protected Rapamune

Does he use enteric-coated capsules or something similar? If he does and the rapamycin dose is truly gastro-protected, then 13mg is a pretty high dose.

[kansel]

Go with 12mg every two weeks. They (attia podcast) almost but agreed in high doses at longer intervals.

[idb]

Ya, that’s what I’m leaning towards…thanks.

[kansel]

BTW I’m doing 10MG with GFJ+EVOO. I’m thinking of upping it to 12-15mg with GFJ+EVOO and only do it once per month. I think I’ll give it a try that way see what happens.

[kansel]

BTW, if you have never taken RAPA before it is suggested you start low dose and up it. When I started I did 2MG first week then 3 next week and then 5 and after a while went to 10

[RapAdmin]

@desertshores

Does he use enteric-coated capsules or something similar?

I’m sure he’s just using Rapamune, and he’s using layman’s terms for the nanocrystal technology they use: Rapamycin and NanoCrystal Formulations

[scta123]

I believe BJ is testing a new weekly protocol. One week 12mg, second week 6mg or something similar. Check again his blueprint notes.