Efficacy of a wide range of things, from sleep & diet to supps & meds, may depend on timing

A study on epilepsy was published comparing gene expression in parts of the brain where seizures developed with adjacent healthy tissue (Li et al., 2017). It was in humans, so they couldn’t really have proper controls, because what healthy person would volunteer to have some of their brain chopped out?

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They found the core circadian rhythm gene CLOCK was reduced in epileptogenic regions of the brain compared to healthy nearby tissue. It could be that this is just the way it is in healthy people, or that the seizure itself reduced CLOCK not vice versa. But the researchers followed-up with animal models lacking CLOCK in either inhibitory or excitatory neurons and showed mice lacking CLOCK in excitatory neurons had a lower seizure threshold and a more severe condition (suggests causation). They had worse seizures in the dark phase, similar to the findings in humans.

Bmal1 is CLOCK’s partner in crime. They also jack up REV-ERB, which ends up shuttin’ ‘em down in circadian fashion.

A semi-related study showed that a transporter which shuttles certain drugs out of the brain was under circadian control, and an anti-seizure drug was significantly more effective when administered when expression of that transporter was lowest (Zhang et al., 2017). If this means a lower dose can achieve the same efficacy, possibly with fewer side effects, I’m all for it.




There is an interesting interaction between brain-stuff (epilepsy in this case, but also cognition, memory, etc.), circadian rhythms (timing of seizures and LITERALLY EVERYTHING ELSE), and diet (keto, low GI, MAD, etc.). It has been speculated by some (myself included) to share some aspects with “brain fog” as well.



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The deeper I dive into this, the simpler my pan-health mantra has become: don’t eat like a child and CIRCADIAN RHYTHMS haha get some blue blockers 🙂

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Some prior musings on the topic:

Circadian Mismatch and Chronopharmacology (scroll down to part 2 for some actual examples of dose-timing for various drugs)

Ketosis: anti-brain fog. Neurotransmitters, dietary protein, and the gut microbiome

Ketone bodies as signaling metabolites

Fasting, circadian biology, and epigenetics