Circadian rhythms and ketosis in migraines

Ask almost anyone who experiences chronic migraines and they'll almost always say their latest attack was preceded by a period of poor quality or short duration sleep.

That, in itself, is a hint circadian rhythms may be involved.

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Can circadian dysregulation exacerbate migraines? (Ong et al., 2018)

In this study, sleep characteristics and circadian rhythms were evaluated in 20 chronic migraine sufferers and 20 healthy controls.

They found that, despite similar sleep duration, later sleep timing and circadian dysregulation (as per salivary melatonin) were associated with higher migraine frequency and severity.

It is seriously unpleasant, but migraines can be experimentally induced in otherwise healthy people (eg, Amin et al., 2012). 

PACAP. We've talked about this before. It's a pretty big player in regulating circadian rhythms.

Migraines are also more frequent earlier in the day (circadian) and in longer photoperiods (circannual).

While the precise mechanism is unknown, I suspect it is overlapping with seizure pathology, but with more pain involvement. The drugs for migraines aren't great and never provide full relief. They don't target PACAP; best intervention at this point: prioritize sleep hygiene and be mindful of circadian rhythms.

Another potential intervention: while the initial case reports were in individuals trying to lose weight via clinician-supervised ketogenic diet, they coincidentally noticed reduced frequency and severity of migraines. Follow-up studies have suggested that this may only be partly due to weight loss, with some contribution of ketosis per se (eg, Di Lorenzo et al., 2015 and Barbanti et al., 2017).

enhanced mitochondrial energy efficiency... neuronal excitability, redox balance, inflammation -- many of the potential mechanisms (beyond weight loss) have been reviewed, eg, here

I'm not calling fowl or attributing this solely to weight loss because of the many well-established effects of benign dietary ketosis on brain in various pathologies. But at the moment, I don't think this had anything to do with evolution -- more like a lucky coincidence for epileptics, migraine sufferers, various inborn errors of metabolism, etc.

What do you think?

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