Do we have any data about what drugs shouldn't be combined? (toxic combinations where 1 + 1 = -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)

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?


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

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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:


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