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.

 

calories proper

 

 

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  • It tastes like some horrible cough syrup. But you have elevated ketones for like eight hours, which is far better than the ketone salts.
    The big thing I noticed was that my sleep was deeper and reminded my of teenage sleep. Probably worth having around just for that.

    • TechnoTriticale

      Are there any ketone ester products available yet, other than research materials? I know people are working on it.

      There are a number of BHB salt products, of course, but only two of those will tell you how much BHB you’re actually paying for, and most have excess calcium.

      • No esters commercially available yet, but the one I tried tasted like poison.

        Not commercially viable, either.

    • WHAT tastes like horrible cough syrup ???

      • I believe it is “(R)-3-hydroxybutyrate-R-1 ,3-butanediol monoester” from here: http://www.ketoneaid.com/
        …and “horrible cough syrup” is putting it kindly

        • Eric – Golden, CO

          You can get 1,3 Butanediol CAS#: 107-88-0 fo cheap here: http://www.ketoresearchchem.com/mobile/Product.aspx?ProductCode=BD
          I got some back in 2013. This company is Patrick Arnold. It is the worst tasting keto product I’ve ever tried. And as Dom said to me, ” This stuff is nasty tasting. It’s a great way to increase ketones, but not ideal for performance”

          • oh, cool, thanks.

            How much did you take and how high did your ketones go? (just curious)

          • Eric – Golden, CO

            1 Tbsp 0.4->0.7, 3 Tbsp 0.6->1.3:
            I’ve also mixed it 1:1:1 with MCT, KetoForce and 1:1:1:1 with MCT, KetoForce, annd KetoCaNa.
            With 1Tbsp for each of the 1:1:1 0.4 ->1.4
            Those were all the measurements I did. I don’t seem to get extremely high ketones even with multiple day fasts or after hours of running my peak is 1.5-1.7. Only after 50-100+ mile bike rides have I gotten numbers in 3,4,5,6. (endogenous).

          • interesting. Thanks!

        • Thanks…

        • I just went the research chemical route. They appear to be out of stock right now at Amazon. I don’t like the taste, but I’d rather it get cheaper instead of being really expensive and taste better.

  • Charles Richardson

    Ya know what else raises BHB? Probiotics/prebiotics.