I just responded in my journal, I guess it makes sense to throw this into the general discussion here.


Fat adapted vs being in ketosis...

Okay, I'll bring Arctic mammals into this. If you look at seals and other sea mammals in the far north, these are very fat adapted animals. Some whales will basically be fasted for months every year, due to the changing seasons. These animals will get the vast majority of their energy from body fat.

Due to a large metabolism vs. brain size, these animals can pretty much run their brains strictly on glucose, even when fasting, sourcing the glucose solely from the glycerol contained in their on triglyceride stores, all this without resorting to ketosis. Our much larger relative brain metabolism means we can't do this, so we much more readily enter ketosis. But ketones aren't a prerequisite for fat adaptation as such.

Phinney and Volek have looked at ketoadaptation. Take some cyclists, put them on a ketogenic diet, at first they're going to suck because their bodies aren't used to the diet, after some weeks performance will recover. This is probably a case of combined fat and ketoadaptation--most calories will come from fat, if there's not enough glucose coming in to feed the brain, some portion of brain metabolism will come from ketones.

Muscle and heart can get their energy from mitochondria primarily through oxidation of fat or glucose. Adaptation to fat can spare both glucose and ketones for brain and other tissue that needs it more. So you've got this thing where, if muscle becomes fat adapted and spares glucose, becoming fat adapted could actually decrease ketone production.

So I'd say--while what Phinney and Volek advocate is both keto adaptation and fat adaptation, you do have to separate the two, and there's no reason you couldn't be fat adapted without being very ketotic. Could you be keto adapted without being fat adapted? Probably not in the usual course of events. Old fasting studies showed ketone production at maximum on day three of a fast. Blood ketones didn't reach a steady state maximum until day ten or so, the explanation was that early in the fast, muscle used ketones for energy. There's an adaptation away from ketone use by muscle--further into a fast, or further into adaptation to a ketogenic diet, muscle starts converting the acetoacetate that's a more direct fuel source for mitochondria into beta-hydroxybutyrate. That takes an extra enzyme to metabolize, this is something that can be upregulated in the brain, and the whole process allows those ketones to be spared for the brain.

The Nad+/Nadh ratio affects the tendency in muscle to convert acetoacetate into beta-hydroxybutyrate, and fatty acid oxidation affects this ratio--when muscle is getting lots of energy from fat, the more readily metabolized acetoacetate is pushed towards beta-hydroxybutyrate. So part of ketoadaptation is actually a consequence of fat adaptation that keeps the ketones from being wasted. But again, this also spares glucose.

Some made up numbers as an illustration. Somebody eats 70 grams of carb a day, otherwise a very high fat diet. At first they are not fat adapted--they may enter ketosis more readily, because their body isn't sparing that glucose yet. As they become more fat adapted, ketones may actually decrease.

Or they eat 20 grams a day. How do things go? Suppose they're in ketosis at first. What happens later on, if they keep eating exactly the same way? Okay, they become fat adapted. Less wasting of glucose and ketones. Do ketones go up or down? I think either direction makes sense, a person able to produce enough glucose for their brain, once it's not being wasted by other organs, may reduce ketone production. On the other hand--like a starving person, another person's ketones might go up with time, if the ketones are spared for the brain and they're really not capable of coming up with enough glucose, even with fat adaptation. This is more the situation you hope for if you're doing a high ratio 3:1 or 4:1 etc. therapeutic diet for epilepsy or cancer, there are some anecdotes for bipolar at a higher ratio, I'm one of them.

Sometimes people will say that measured ketones go down because they're being more "efficiently" used for energy. This is doubly untrue, first, entry of ketones into various cells depends on there being a chemical gradient, a significant difference in concentration between the exterior and the interior of the cell. The second problem is what I've outlined above, keto-adaptation doesn't involve increased use of ketones across the whole body, it involves a sparing of ketones just about everywhere but the brain.