http://www.fasebj.org/content/29/1_...nt/715.17.short

Very interesting, but I cannot seem to figure out what ketone esters are and how they relate to metabolism. Is it possible to get ketone esters from any food products? Or are they a by-product of any digestive process? This one sounds like it was manufactured for the purpose.

Basically, what I want to know is--If I'm a butter snacker, is it rotoring out my veins or do I need to add some coconut oil?

Neither. Once it's a ketone, the liver won't metabolize it. With coconut oil or butter--the ketones won't be produced unless the liver metabolizes the fat--leaving the potential for cholesterol production, etc., in the process of breaking down the fat while producing the ketones. Of course that depends on whether their explanation for the decrease is correct--that it's caused by decreased substrate availability in the liver--rather than there being some sort of signalling cascade that reduces cholesterol production in the liver, responsive to ketones.

There might be trace amounts of ketone in food, but nothing like supplementation.

One potentially nice thing here is that while the ketones might be decreasing cholesterol production in the liver itself, they have the potential to provide substrate for cholesterol production in other parts of the body, like the brain.

It will be interesting to see, when the group later releases a longer paper, what happened to people's insulin levels in the study.

I understand the concept of ketones, I'm just trying to figure out what a ketone ester is and how it fits into the equation. Apparently it is an artificially produced chemical that is rapidly broken down into ketones? The whole point being to get the benis without actually eating a ketogenic diet it seems. This article provided a bit of insight:

http://high-fat-nutrition.blogspot....-dangerous.html

So are they investigating the use of these ketone esters as a possible supplement (to SAD?) or the possible benefits of a ketogenic diet? Seems like the former.

I think though, in the same way that early studies showing an advantage to lowering cholesterol through drugs lead people to jump to the conclusion that lowering cholesterol through diet was a good idea--if supplemental ketones catch on as a treatment, that might give dietary ways of entering ketosis a boost in popularity--whether for the right reason or not. Even if part of the purpose of the studies is to find a way to put people in ketosis without risking a high fat diet.

In the case of type II diabetics--it might just take a bit more to get into ketosis. Or take somebody like Jimmy Moore, he just did a 17 day fast, while his wife was doing a low-carb autoimmune diet--and her ketones and blood glucose were around the same level as his.

Some of the therapeutic ketogenic diets are very aggressive. If a person needs to eat 90 percent of calories as fat--and even then, still has to watch their calories, to get the level of ketosis/suppression of glucose metabolism desired--there's a case where being able to eat a bit less stringent diet would be nice, and maybe compliance more likely. In the extreme, a person might be forced to choose between optimizing for ketosis, and getting in enough protein to sustain lean mass.

And I guess if somebody can eat a high carb diet, and still get some benefits from exogenous ketones, that's something worth knowing. There will always be people willing to take the supplement, but not willing to change their diet. I know people who think a low carb diet would improve their cholesterol--but they take statins, they think it's "instead," that it will protect them from their diet choice. It'd be nice if ketone esters actually provided some of the protection they hope for from statins.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821009/

This is a paper on ketone esters by Veech, and yeah, there is some prejudice against a ketogenic diet there;



It would be interesting to see, in people who do get elevated cholesterol and triglycerides on a ketogenic diet (I think the second is rarer than the first), what happens with ketone esters being added in.

So, if we eat ketones, and the liver responds, then the liver has the ability to see ketones coming in. Did they measure insulin?

Injecting ketones drops BG and insulin. Eating ketones should have the same effect. It has the same effect on BG in this experiment. Insulin regulates triglycerides metabolism, so it should have the same effect on insulin too.

If I'm not mistaken, ketones can't be metabolized into cholesterol. So their idea of substrate-driven regulation is obviously wrong. So it must be all about signaling. So the liver must have the ability to see ketones coming in.

https://en.wikipedia.org/wiki/Meval...hi_def_tiff.tif

https://en.wikipedia.org/wiki/Ketog...Ketogenesis.svg

Check out the ketogenesis and mevalonate pathways. Up to the point of HMG CoA, it's identical. At that point, HMG CoA lyase can produce an acetoacetate and an Acetyl-CoA, or HMG reductase produces mevalonate.

I first found the Hyperlipid blog when Peter commented on a Dr. Davis post about using niacin to reduce ldl and triglycerides, and raise hdl. Peter was commenting that beta-hydroxybutyrate was also a ligand for certain nicotinic acid receptors (and maybe they should have been named ketone receptors in the first place, for all we know).



One thing nicotinic acid signalling does is reduce lipolysis, and this makes sense when ketones are high, usually--since, if they weren't already at an adequate level, then where did all those ketones come from?

That GPR109A receptor is found in the liver (at least in mouse livers), at much lower levels than in adipocytes. So there's at least one way for the liver to directly sense the ketones. But reduced lipolysis, leading to reduced beta oxidation and reduction in the Acetyl-CoA needed for cholesterol production in the liver also makes sense.

Okay, here's some full text, more detail on reduction of lipolysis through this receptor;

http://www.jbc.org/content/280/29/26649.full



Lowered triglycerides could be secondary to a reduction in lipolysis. Not necessarily as bad as it sounds, this might make for a more rapid depletion of glycogen stores between meals and especially during the longer fast of sleep. That might reduce blood glucose and insulin, but I might be stringing together too many mights here.

If both nicotinic acid and ketones act on the same receptor, and if nicotinic acid has the ability to inhibit lipolysis, then ketones also have this ability, which gives credence to my paradigm, which says blood ketones level regulates ketogenesis in the liver through a negative feedback loop, i.e. more ketones, less ketogenesis, and vice versa.

Since eating ketones drops BG in this experiment, it must also act on glycogen/glycogenolysis in the liver as well. There must be a pathway. If insulin is involved anywhere in that pathway, it opens the door to insulin degradation, we get lower insulin.

Glucose likely has the ability to inhibit ketogenesis too, likely by using insulin too. But then, it could also have the ability to inhibit insulin degradation, we get the typical profile of low ketones high BG and high insulin. As glucose drops, there's less inhibition of insulin degradation, insulin drops, ketogenesis picks up, negative feedback loop, all things are now regulated. Inject/eat ketones, ketones force the feedback loop.

As for cholesterol, if insulin is involved anywhere in that pathway, and since excess glucose raises insulin, it follows that merely eating carbs will disrupt cholesterol metabolism.