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Comment by Knufen | Hacker News Reader

Organic/medicinal chemist here. Some toxin, endocrine disruptors and many other things have widely variable toxicity curves. Something we often see is U curves. With high toxicity in both small and high doses. The small doses can induce cascade effects (like hormones).

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I’m having trouble imagining how a smaller dose could cause a larger effect, can you elaborate some more on the biochemical mechanism for that?

This effect has always puzzled me, so much that initially thought it was pseudoscience (like homeopathy). I mean, in a real U curve, the highest effect is at a zero dose and it makes no sense.

But it looks serious, peer reviewed papers and all that. The main reason seems to be that at a low dose, the chemical doesn't trigger "defense" reactions and can do its thing unimpeded (high effect), on a medium dose, our body starts to notice and dampen the effect (low effect). High doses are simply overwhelming and the effect becomes high again.

I still think there is a lot of pseudoscience around that effect that helps selling a lot of "natural", "detox", etc..., but I don't think all of it is bullshit anymore.

As other posters note some feed-forward defense mechanism requires a larger dose to elicit a response. Sometimes small doses have a cascade effect meaning A->2xB->6xC etc whereas a larger dose would activate a feed-backward mechanism between B and C.

A classic example is endocrine disruptors (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036398/), a small dose induces a hormonal response, a medium dose the body fights due to detecting it as foreign and a high dose is just regular toxic. Please note this is somewhat simplified but used as an example.

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