The Stack That Almost Crashed
Berberine triple-threat discovery
The 30-Second Version
Duration: 40 seconds Compliance: "Berberine" is an herbal supplement, fine to name. DO NOT name what it was interacting with (Tesofensine). Keep the interactions described in general mechanism terms.
"A supplement literally everyone recommends almost crashed my entire protocol.
Three separate interactions nobody warned me about.
One: it was raising the effective dose of something else in my stack by 40 percent. Silently.
Two: it was hitting a brain pathway that was already getting hit by three other things I take.
Three: it was inhibiting the same cellular target as a compound linked to neurodegeneration in research.
I caught it through systematic analysis - not because I felt bad. I felt fine. That's the scary part.
My medical team and I replaced it with something that gives the same benefit through a completely different mechanism. Problem solved.
If you're taking more than 5 or 6 things - supplements, whatever - you need to check interactions.
Your stack isn't as safe as you think."
Last line (quotable): "Your stack isn't as safe as you think."
A commonly recommended supplement was about to crash my entire protocol.
Three separate dangerous interactions. Nobody warned me. I caught it through systematic analysis. Here's what happened. 🧵
I was taking berberine. Everyone recommends it. Blood sugar support, AMPK activation, gut health.
What nobody told me:
Problem 1: Berberine inhibits CYP3A4 (a liver enzyme). One of my other compounds is metabolized by CYP3A4. Berberine was raising its effective dose by ~40%. Unknowingly.
Problem 2: Berberine inhibits MAO-B.
I was already on several things that affect serotonin. Adding an MAO inhibitor to that stack increases serotonergic risk significantly.
Problem 3: Berberine inhibits mitochondrial Complex I. That's the same target as rotenone - a compound linked to Parkinson's in research.
Three problems. One "safe" supplement.
The fix: I replaced berberine with MOTS-c.
MOTS-c activates AMPK (same benefit as berberine) but through an entirely different mechanism - folate-AICAR pathway instead of Complex I inhibition.
All three problems solved in one swap.
The lesson: individual supplements aren't dangerous. COMBINATIONS can be.
Nobody tracks interactions across 30+ compounds. Your doctor doesn't. Your naturopath doesn't. The Reddit threads definitely don't.
This is why I built AI agents to cross-reference my entire stack against pharmacogenomic databases. And why I'm making those tools open source.
If you're taking more than 5-6 things, you should be checking interactions. Not just drug-drug. Supplement-drug. Supplement-supplement.
Your stack isn't as safe as you think.
This is what I put in The Manual every week.
Subscribe to The Manual →