#41

As always, rapamycin is a candidate to be the new drug of the century. What is the FDA still waiting for? New rapalogs need to be developed urgently

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#42

Maybe the dose is daily b/c their lifespan average is about 1/7 th of ours. 1 week of our life approximates 1 day of theirs…However, this still doesn’t explain the extremely high dose.

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#43

10mg/day?
I take about 12mg once every two weeks. I feel poorly for 12 hours (I can sleep through most of that). Then I feel sore for 2 days from my lifting workout 24 hours before Rapa due to slower recovery. 4 days after my Rapa dose I’m back to normal and can start lifting again (rode the bike for 4 days after Rapa). I wouldn’t live my life like that all the time to get 15 more years.

This is why my rule is nothing just for longevity. I get an immediate benefit plus a longevity potential, or nothing.

7 Likes
#46

Can you talk me through how a CYP3A4 inducer reduces HL? Which one do you use?

1 Like
#47

It’s a meta-analysis by researchers from the UK, Pakistan, Australia, and Malaysia, in the journal of the European Society for Clinical Nutrition and Metabolism (with a good impact factor of 6), published by Elsevier: https://www.sciencedirect.com/science/article/abs/pii/S2405457721003077

So, it’s not Nature, but it’s descent. (And certainly better than the vast majority of papers (and tweets…) people base their health decisions on…) However it’s a meta-analysis, so the risk is always “Garbage in, garbage out”. I don’t have access to the whole text. We should look at the six trials included to see if they are of good quality.

(The paper was good enough to convince Bryan Johnson and his doctor to try/use lactoferrin.)

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#49

Thanks. The trials look good (but small-ish). Most in infants indeed but 3 in adults:

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#50

I’m starting to think so, another meta-analysis of small trials not consisent with larger trial?

We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233).

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32221-9/fulltext

No 43% reduction here.

#51

This trial was not included in the meta-analysis. Although the result is negative, it’s a very specific population: “very preterm infants born before 32 weeks’ gestation in 37 UK hospitals and younger than 72 h”!!! I don’t think it can be generalized to adults.

#52

I think it wasn’t included since it didn’t fit their criteria for URTI.

Sure, but most of the trials in that meta-analysis were in infants, too.

Two of the adult trials failed, one succeded.

The nearly 50% reduction was pretty unbelievable to start with, IMO.

1 Like
#53

No, 2 succeeded, one failed and the one that failed was in critically ill adults: Breaking: 15% Healthy Lifespan improvement via Rapamycin seen in Marmosets - #49 by adssx

#54

No, that’s not 10 mg/day for a 60 kg human. The metabolic scaling factors in this article you linked to are not correct.

Given that marmosets weight about the same as lab rats, they would have a metabolic scaling factor that is very similar, or close to 3.4. With that scaling factor, 1 mg/kg would be equivalent to around 18 mg for a 60 kg human. That’s pretty high but not super high. The thing that makes the dose more difficult to translate to humans is the fact that they were fed daily. Without knowing how fast they metabolize rapamycin and therefore what their rapamycin half-life is, it’s hard to translate this to humans. Are they clearing out the dose and reaching a very low through level within 24 hours before the next daily dose, or are they not clearing it out and therefore getting an accumulation of rapamycin in the blood with constant exposure? That’s something I would like to know.

6 Likes
#55

The duration of summer colds was shorter in the 600 mg group (2.0, p = 0.036) than in the placebo group (3.0). No significant differences were observed in the prevalence of infectious diseases or changes in immune parameters.

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#56

So you say the FDA is not correct?

#57

Ah you’re right, the only difference is in the length of the disease post-infection.

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#58

Yes. They even say themselves that it’s not correct. If you look at the details of how they created the metabolic scaling factors they publish in the tables for people to use, they tell you that they take the correctly estimated scaling factor and add a safety factor to it to make it less risky to use doses estimated by the scaling factor. As an example, the correct scaling factor between mice and humans is close to 7. The FDA knows this but they still give you a scaling factor of roughly 12 between mice and humans. They know that’s not the correct scaling factor but they give you a scaling factor of 12 because if you use that one, you will take a lower dose and have lower chances of harming yourself. They assume people don’t know how to err on the safe side.

5 Likes
#59

I’m a little unclear on exactly why you say this (below) is wrong. In their table calculating the HED from the rat or the marmoset is the same at 6.2…

JBCP-7-27-g002
JBCP-7-27-g0021010×415 86 KB

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#60

Yes like I said, rats and marmosets weight about the same so they should have the same scaling factor, although the factor is too big. The reason I think the scaling factors in the table are wrong is what I said above, that they deliberately add a safety factor to the correct factor, the result being that all the scaling factors in the table are too big. I know this sounds strange, because they don’t mentioin this in the table, however, if you look at studies on scaling factors that explain how these factors were created, you will find that the FDA table is based on the correct scaling factor plus a safety factor.

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#61

You can even calculate the scaling factors yourself based on the differences in average calorie intake and body weight of humans vs animals and this will also make it clear that the factors in the FDA table are too big. I’ve done that myself in the past.

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#62

They have the same scaling factor: 6.2. (Even though marmosets weigh 2x more than rats)

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#63

There are different types of marmosets, and some of them weight the same as lab rats. In any case, a 2x difference in body weight would only amount to a lot less than 2x difference in the scaling factor.

1 Like