Ketones, Cancer, and the NLRP3 Inflammasome

“Check ‘em all. Do the work. There’s no room for cherry-picking here.

LOOK THE GIFT HORSE IN THE MOUTH”

A few years back, researchers discovered the pseudo-ketone beta-hydroxybutyrate suppressed the NLRP3 inflammasome (Youm et al., 2015). NLRP3 is notorious for aggravating gout symptoms, so it was like: “Yay! A potentially clinically relevant use for ketone supps!” (I think there might be other applications as well, but that’s for another blog post).

Ketones, NLRP3, and IL-1b

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It’s thought that NLRP3 is around during active flares, so gout sufferers would stay on their regular meds and take ketone supps as needed – this is important because from what I understand, gout flares really suck, some people get them frequently, and ketone supps aren’t covered by insurance [yet?].

 

Besides certain aspects of the ketogenic diet, I’m also interested in “Ketone bodies as signaling metabolites.” From this perspective, ketones are quite interesting, interacting with circadian biology, HDACs, ChREBP, epigenetics, inflammatory pathways, etc., etc.

 

However, there may be a dark side, or rather a very large confusing gray area when it comes to ketones, cancer, and the NLRP3 inflammasome…

Remember that whole “keto-for-cancer-because-everything-is-Warburg” thing? …it’s not really a thing (more on this below).

 

 

 

This paper showed NLRP3 is upregulated in a model of squamous cell carcinoma (ie, cancer), and an inhibitor of NLRP3 was effective. Cool, all pre-clinical & in vitro stuff, but maybe these researchers could test beta-hydroxybutyrate in their model. I say this because there are many different types of cancers, any potential therapeutic avenue should be tested in as many models as possible. In addition to beta-hydroxybutyrate, there are even a couple other NLRP3 inhibitors… which ones might work for which cancers, if any?

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I’m also open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

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