#1

From what I know some combinations can cancel each other:

    1. AKG and berberine alone extends lifespan in mice but AKG + berberine give 0% lifespan extension.
      Brian Kennedy said “we had problems picking good combinations” - but I can’t find any other bad combinations that they were testing
    1. Metformin and Rifampicin increase lifespan at C Elegans individually by 20% but combined they extend lifespan by 5%
    1. FGF-21 and Klotho gene therapies alone in mice improved kidney and liver function but combined they were worse than placebo

Probable explanations:

  1. Maybe Berberine increases AKG itself, so organism have too much AKG?
  2. Maybe Rifampicin increases Metformin blood level and makes it toxic? (Metformin increases lifespan only at ideal dose - 70% higher Metformin dose and it is toxic (with Rapamycin dose can be 3x higher or lower than ideal and it still works))
  3. FGF-21 and Klotho have very similar functionality - so combining them is bad

On the other hand, some combinations that are positive:

    1. Rapamycin + Acarbose in mice (especially in male mice)
    1. Glycine + NAC - has 20% effect in mice lifespan - but not confirmed by NIA ITP yet - both Glycine and NAC extends lifespan in mice alone by about 5%
    1. Rapamycin + Lithium + Trametinib - in Drosophila each compound extended lifespan alone by 13%, when combined it was 45% lifespan extension (probably the most in Drosophila beyond genetic manipulations)
    1. Rapamycin + Rifampicin + Allantoin - each extended lifespan in C Elegans by about 20% - combined they gave about 60% life extension (the most so far beyond genetic manipulations)
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Detrimental effects of overdoing longevity interventions?
Combine them all! (Longevity Drugs and Supplements)
#2

Great Topic!

I would also add that Rapamycin + Metformin increases lifespan in mice as well.

Any other combinations that we should avoid or steer towards?

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#3

It is interesting that rifampicin induces hepatic CYP3A4, metformin, like berberine, on the contrary, inhibits CYP3A4

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#4
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#5

The video says ‘Don’t take K and D together’ Is this true? Where’s the evidence? I’ve been taking D3+K2/MK-7 at the same time for several years. :frowning:

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#6

I mean, Morten and Matt Kaeberlein both have datasets of negative synergies of metformin - ask them

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