A 2022 LessWrong post on orexin and the quest for more waking hours argues that orexin agonists could safely reduce human sleep needs, pointing to short-sleeper gene mutations that increase orexin production and to cavefish that evolved heightened orexin sensitivity alongside an 80% reduction in sleep. Several commenters discussed clinical trials, embryo selection, and the evolutionary puzzle of why short-sleeper genes haven't spread.

I thought the whole approach was backwards, and left a comment:

Orexin is a signal about energy metabolism. Unless the signaling system itself is broken (e.g. narcolepsy type 1, caused by autoimmune destruction of orexin-producing neurons), it's better to fix the underlying reality the signals point to than to falsify the signals.

My sleep got noticeably more efficient when I started supplementing glycine. Most people on modern diets don't get enough; we can make ~3g/day but can use 10g+, because in the ancestral environment we ate much more connective tissue or broth therefrom. Glycine is both important for repair processes and triggers NMDA receptors to drop core temperature, which smooths the path to sleep.

While drafting that, I went back to Chris Masterjohn's page on glycine requirements. His estimate for total need [...]

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Outline:

(01:49) Glycine helps us sleep by cooling the body

(02:26) Glycine cleans our mitochondria as we sleep

(04:12) Most people could use more glycine

(05:28) Fever is plan B for fighting infection; glycine supports plan A

(09:28) Glycines cooling effect via the SCN is unrelated to its immune benefits

(10:35) Glycine turns out to be a legitimate antipyretic after all

(11:51) Practical considerations

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First published:
March 22nd, 2026

Source:
https://www.lesswrong.com/posts/87XoatpFkdmCZpvQK/is-fever-a-symptom-of-glycine-deficiency

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Narrated by TYPE III AUDIO.

“Is fever a symptom of glycine deficiency?” by Benquo

LessWrong (30+ Karma)