Ketones, NLRP3, and IL-1 beta

Interleukin-1 beta: produced by activated M1 macrophages, classical fever-inducing cytokine, mediates cellular inflammation, and induces COX-2 (target of NSAIDs).  Also involved in autoimmunity.  You don’t want none of it but you certainly don’t want a lot of it.

The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasone-mediated inflammatory disease (Youm et al., 2015)

This is a very specific effect: 1) many structurally similar compounds don’t block NLRP3; and 2) beta-hydroxybutyrate doesn’t block activation of other inflammasomes.



“In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1b secretion in mouse models of NLRP3-mediated diseases such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome and urate crystal-induced peritonitis. Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.”




Activation of the NLRP3 inflammasome is responsible for IL-1b secretion by activated macrophages.


If you have gout, certain autoimmune conditions, or maybe even Alzheimer’s, this may be a viable #context for ketone supps.  The authors used 1,3-butanediol diesters:



^not commercially available yet, but mustn’t taste too bad because the mice actually ate it…



Postprandial macrophage-derived IL-1b stimulates insulin, and both synergistically promote glucose disposal and inflammation (Dror et al., 2017)

Another downside to chronically elevated IL-1b is type 2 diabetes.  This study showed that hyperglycemia induced NLRP3 and IL-1b secretion which enhanced insulin secretion and glucose uptake into macrophages, which caused more pro-inflammatory effects.  A vicious feed-forward cycle.


“Postprandial inflammation might be limited by normalization of glycemia, since it was prevented by inhibition of the sodium-glucose cotransporter SGLT2.”

Eat during the day, SLEEP at nightSunlightNo junk food.  Exercising after meals can be an effective band-aid because contracting muscles take up glucose independently from insulin, so it works even in insulin resistance.

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calories proper


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