Low dose vs. High dose

It seems to me lot of people are pushing dose up in spite of results at lower dose…Dr. Green originally did 6mg/week which he says was “aggressive” and says he had great results in 4 months time…now that dose seems to be on the low side, and even he is increasing his dose markedly…why increase if lower dose does so well?

My question basically is do we have observational info from users doing 6mg/week or biweekly that says they see definite results from this dose and if so, why increase the dose? I know that dose/response varies by person b ut if it works at 6 or 8 mg/week why go higher?

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quote from PAMPAGUY of LongeCity forum: "Dr. Blagosklonny and Dr. Green have both changed there dosing schedule to 20 mg. every 12-14 days. The reason for this is to get the “spike” of rapa in the blood to get past the blood/brain barrier in the brain to inhibit mTOR1 in the hippocampus portion of brain which is thought to control ageing. "

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back to my original question…Green states that after 4. months on 6mg he had a variety of great results which would certainly indicate an effect on aging…others do as well. Green said he lost 30 lbs, reduced waist size 5 inches, increased cardiovascular endurance a lot, and more.

soooo…while I understand the BBB reasoning (theory) what more are they looking for?

I know what they are doing with increased dose, that is the reason for the question.

I think rapamycin experiments on mouse show better longevity results at high doses than low doses. Rapa doctors like to push higher doses to get better results in health aspects before getting side effect. But i think the maximum doses is 45mg/twice weekly, because that’s what cancer patients are taking, and they get gastrointestinal side effect if doses are higher than 45mg. Keep in mind that a lot of reports show that old folks and young men respond differently to rapamycin doses.

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Hi Alex, welcome to the site and thanks for posting.

The reason people are pushing up the doses is that in the mouse studies, the higher the dose the longer the lifespan. In males at least they have not found a higher dose that did not further increase the lifespan.

Search here on the site for “higher dose” and i think you will find that research.

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Human studies show that rapamycin is associated with an increased risk of death in transplant patients (and not just from infection). Other mTOR inhibitors seem to have the same effect. This perhaps indicates that the mouse study results might not translate to humans.

Of course, high-dose rapamycin could have totally different effects in non-transplant patients, but this is still Bayesian evidence that high doses (especially when taken frequently) might not be beneficial to healthy humans. It’s probably stronger Bayesian evidence than mouse studies.

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You question is answered below, where I explained why the experts are going to 20 mg every 14 days.

From the study quoted above:

So it’s heart disease and infection. Thus, critically important to monitor lipids while taking rapa, treat if elevated and continue healthy diet and exercise. I don’t know if the increased infection risk holds for non- transplant patients, since they typically use multiple immunosuppressive meds and/or higher doses of rapa.

Also, this was interesting:

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Or it could be that the transplant patients are not in as good of health which is why they are taking rapamycin. Correlation is not causation.

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Whether a dose is considered high or low is relative we’re used to hearing initially of 1 mg or 5 mg rapamycin so 10 mg seems like a lot… Vitamin C is taken at 1000 mg a day.

Its all about whats the suitable dose for optimal results

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Hi Brad, welcome to the forums, and thanks for posting.

The studies that @Natalia has mentioned are interesting - but obviously the populations and dosing protocols are very different (compared to the use of rapamycin for anti-aging applications).

We know that ongoing daily, high dosing of rapamycin will eventually cause inhibition of mTORC2, thus immune system suppression… so people don’t do this type of dosing in anti-aging, and therefore at much lower risk from the infections noted.

Also - in the second paper, the FAEs (fatal adverse events) are very specific to a type of patient as it specifies below (with advanced solid tumors) - so unlikely to be generalizable to healthy populations taking rapamycin on pulsed, anti-aging protocols:

Conclusion

With the present evidence, the use of mTOR inhibitors seems to increase the risk of FAEs in patients with advanced solid tumors.

From this paper.

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