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naraburns  nihil supernum  1yr ago (text post)   5896 thread views

Small-Scale Question Sunday for January 22, 2023

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I'm not certain to understand what your goal is with that question,

a pharmacological causative model is heuristically useful to make predictions, about effectiveness for condition X and to establish a safety, tolerance, toxicity and interaction profile.

All those things are useful but mostly unecessary for the layman.

If there is a non-negligible community that takes plant X since years in quantity Y and that doesn't report huge terrifying side effects and that they report potent effectiveness then its probably worth a try for acute use although for long term use there will always be a toxicity/accelerated ageing question but in many cases we never know for certain however in most cases we do know reasonably somewhat the safety profiles.

It has actually become very rare to find phytochemicals that have not been extensively studied regarding their pharmacology and hence the causative model is often well established assuming you take time to research the research.

But beyond annecdtotal evidence, doing a blind test scientific trial about wether X is effective for Y, e.g. depression is very cheap and therefore even without said causative model we often know wether X has elicited a potent response for Y in N people empirically following precise protocol.

Empiricisms as always trumps a priori reasoning regarding effort efficiency and indeed people should considering the mostly safe profile of phytochemicals (generalization see e.g. cyclopamide https://en.wikipedia.org/wiki/Cyclopamine#/media/File:Cyclopelamb2.jpg) play much more the lab rats, this would drive very significantly the speed of empirical scientific research and therefore discovery of treatments for ineptly considered incurable diseases.

edit:

only recently did we learn that tryptophan will selectively unbind with albumin at the blood brain barrier

What does that imply? We already knew tryptophan cross the BBB. You mean the competition with tyrosine?

only recently has the consensus shifted to serotonin deficiency lacking a role in depression (although I have my own views on this).

What?

Serotonergics are euphorisant see e.g. MDMA, MDAI, 5MAPB, shrooms, etc

The effect of SSRIs is less intuitive (reduction of sert receptors density) but still sert driven.

No, the original thought on how tryptophan crosses BBB was extremely murky, because it a lesser competitor to other LNAAs. So we knew that we could toggle greater crossing by reducing the competitors (see wurtman lab) by flushing LNAA to to muscle via pure carbohydrate insulin spike (tryptophan stays bound to albumin). We also knew exercise increases serotonin synthesis, and tryptophan depletion decreases this. What was relatively new, I believe from 2015-2018, was that tryptophan selectively unbinds with albumin at the BBB, so the albumin-bound tryptophan will release uniquely there. It’s an example of how we know little about the mechanisms of serotonin. There’s also controversy about whether how important T:LNAA ratio is to sum total T, the mice studies are not clear. Maybe I’ll dig up the metastudy I read a bit ago

Re: serotonin, I don’t actually disagree, but the consensus I read was that “more serotonin” does not decrease depression.

https://www.nature.com/articles/s41380-022-01661-0

The distinction I would make is that these studies are flawed and there is actually very limited ways to organically increase serotonin production in the brain: increasing dietary T:LNAA ratio (also found to be widely healthful per a large Japanese population cohort study, on things like sleep); using fruit to flush LNAA muscle tissue; or exercise (somehow; possibly by using up LNAAs).

There are some other interesting things about this: certain human domesticated crops have higher tryptophan than wild-type; there’s a possibility fruit consumption in humans is kind of evolved to increase serotonin, and certain fruit actually have serotonin itself, like kiwi and strawberry, which is fascinating

Thanks Cafe, that is a great comment, exactly the kind of informatively rich comments the motte desperately lacks.

I will give you a proper answer tomorrow but when I said that tryptophan cross the BBB, I actually meant about 5 hydroxy tryptophan (5htp), which has good bioavailability, cross the BBB and bypass the rate limiting enzyme conversion of L-tryptophan to 5htp (which itself downstream will again be converted to serotonin in a rate limited manner)

1998:

https://pubmed.ncbi.nlm.nih.gov/9727088/

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