The conditions under which the liver delivers optimal fuel on demand may be the conditions under which it evolved.

When you are on a ketogenic diet, the mitochondria in your cells — the parts of the cells that produce energy — actually switch from primarily using sugar for fuel to primarily using fat for fuel. They use fat mostly in a form called ketone bodies (or, commonly, ketones), thus a ketogenic diet.

(See Keto-adaptation: what it is and how to adjust for more on this process of switching fuels.)

Sugar-based living (from a diet with more than about 5% calories from carbohydrate)

When you are using the sugar-based system, all of the cells in your body constantly take sugar out of your bloodstream. It’s hard for your body to keep up, and you need to frequently refuel by eating carbohydrate-containing food.

Getting sugar out of the carbohydrates that you eat is a blunt tool. Unless you eat in a trickling stream, you will consume more sugar than is safe to hold in the bloodstream at once. That sugar has to be quickly removed, because high blood sugar damages your cells. So a flood of insulin comes in to initiate the process of sugar removal. There is some limited storage space in the liver, but when that is full, the rest basically gets stored as fat.

Soon however, the job is done. Your blood sugar is back in a safe range. Your body cells are still demanding sugar, though, and your blood sugar starts to drop too low. Your liver can release some sugar back into the bloodstream, but not fast enough to keep up with demand, so you get tired and hungry, and the process starts all over.

  • People on carbohydrate-based diets typically have to “snack” every couple of hours.
  • Endurance athletes have to stop and eat sugar just to get through their events.

On a sugar-based metabolism, you swing between too little blood sugar and too much, and you have to constantly adjust it “manually” by eating.

Fat/ketone-based living

On the other hand, when you are using the fat/ketone-based system, there is relatively little demand on your blood sugar. There are only a few kinds of cells that don’t have the ability to use ketones (or fat) for fuel, and have to use sugar. That amount can easily be supplied by the liver, which actually manufactures sugar out of protein on demand in response to changes in blood sugar.

The liver can do this at a rate that is more than adequate for normal energy requirements, when the cells that can use fat/ketones are doing so, and thus not putting extra demand on blood sugar.Your body makes significant ketones only when sugar levels are consistently low.

  • It is not uncommon for ketogenic adults to comfortably eat one meal a day.Even my children, when they are ketogenic, can go for several hours at a time without eating.
  • Endurance athletes on ketogenic diets don’t “hit the wall”. They have the ability to tap into fat stores for fuel; a supply that could last even a lean person for weeks.

On a fat/ketone-based metabolism, demand on sugar from the blood is gentle, and your liver refills it smoothly on demand as it is used, keeping it remarkably steady.

An argument for ketogenic metabolism as the default human state

Think about the role of the liver here. When you are not consuming sugar in food (from carbohydrates), your liver orchestrates fuel management precisely.

The liver makes ketones out of fat, thereby supplying almost all tissues with all the energy they need. At the same time, it makes a moderate amount of sugar out of protein. That sugar is stored right in the liver in the form of glycogen. Not much is stored, but it is plenty for the purposes of keeping blood sugar steady, because the blood sugar is depleted slowly: only a few tissues draw sugar from the blood. The rest are using fat or ketones.

This system is efficient and effective.

By contrast, on a carbohydrate-based diet, the storage capacity of the liver overflows. The excess sugar can be stored as fat, but that fat is not used efficiently as fuel. For fat to be used efficiently as fuel, the liver would have to be turning it into ketones at a high rate [1]. But ketones aren’t produced much in a high sugar condition. It takes several days of low sugar intake to start producing significant ketones.

Considering how well the liver manages energy when you don’t eat carbohydrates, and the disruption caused to this system by eating them, I would suggest:

The conditions under which the liver delivers optimal fuel on demand may be the conditions under which it evolved.



As pointed out by Valerie and Ash in the comments, and by Carol Loffelmann on Twitter, fat remains an important fuel in its own right, increasingly so after keto-adaptation. I oversimplified here, but the point about efficient fat/ketone-based metabolism under low sugar conditions still stands.


Consider a popular alternative explanation:

Noticing that excess sugar can be stored as fat, and yet knowing that excess fat storage is not healthy in humans, some people have argued that excess fat storage in humans represents an adaptation gone awry:

The thrifty gene hypothesis supposes that we used to go through periods of feast and famine, getting fat, and then using it up. People who were well adapted got fat easily, and thus survived the famines better. Here and now, where famines are rare, those people would simply get fatter and fatter.

There are at least two problems with this idea. First, the evidence doesn’t seem to bear it: famines may not have been particularly common in Paleolithic times, they don’t appear to have occured at all in some populations that we know later developed obesity on modern diets, and modern hunter-gathers don’t get fat in times of plenty. Second, even if this were essentially correct, that would mean that humans were adapted to go through regular periods of using up the fat. In other words, it would mean humans were adapted to regular periods of ketogenic metabolism! So, at best, this theory supports ketogenic metabolism being a regular part of life in some kind of alternation with carbohydrate-based metabolism.

There are animals that use this kind of strategy. Those animals hibernate. Humans can’t hibernate. Even very fat humans need some level of protein to survive, to make into sugar for the few tissues that need it. If they don’t get it, they will start tearing down essential muscle tissues such as heart, and they will die.

40 replies
  1. Avatar
    Misko says:

    "The conditions under which the liver delivers optimal fuel on demand may be the conditions under which it evolved."

    I've been thinking the same thing.

  2. Avatar
    valerie says:


    you state a few times that most of the energy used by cells under a ketogenic diet comes from ketones. I was under the impression that fatty acids provided most of the energy, with only some of them being turned into ketones by the liver. Do you have any reference on that?



  3. Avatar
    Ash Simmonds says:

    After weeks (months) of an uninterrupted ketotic state most of the body down-regulates ketone usage and becomes more efficient at higher fat usage, with ketones apparently mostly spared for the brain, CNS, and possibly heart. There's a graph of this I've drawn in my head which I should scribble down sometime.

    I don't have a single concise source that I can point to, it's just my elevator pitch take from the variety of literature ranging from old-school epilepsy diets, bodybuilder cutting diets, mostly carnivorous hunter/gatherers (you know, the ones "not in ketosis"), modern keto/paleo stuff, "default" fasting metabolism, and starvation. It's covered pretty approachably by Lyle McDonald, Phinney/Volek, Cahill/Veech, and various current/recent prominent bloggers.

  4. Avatar
    L. Amber Wilcox-O'Hearn says:

    Good point. I'll fix that. I was specifically thinking of the brain when I wrote it. However, the basic argument still stands: that efficient use of fat/ketones doesn't kick in under a condition of high sugar intake.

  5. Avatar
    N Matheson says:

    Nice post, I wonder what state other primates are in.
    Would ketosis as a primary state for hominids have been more important for more evolved hominids more able hunters, erectus? Personally I suspect that like our cousins the chimps early hominids were probably quite capable hunters.

  6. Avatar
    Michael Frederik says:

    I'm not sure if I would quite see it like that. Modern humans might have been big game hunters, or on a more coastally-derived diet, or indeed on a high carb and high tobacco diet (Kitavans), but really, in the scheme of things it is all rather recent. In the long run, despite the constant talk about starches and tubers, aren't we really just evolved from a line of predominantly frugivores? And wouldn't the way our metabolism deals with carbs simply be a preserved adaptation? Not sure what exactly is optimal, but there appear to be 3 ways that work well (i.e., unimpaired glucose regulation): carb restriction, IF, or calorie restriction (or a combination of those). None of those options are even remotely approached under the standard western diet.

    As Richard Feinman has stated, the reaction coming upon a patch of berries (or honey) wouldn't have been moderation. Prior to the agricultural 'revolution' I wouldn't see that as sub-optimal. It might be, but I haven't seen much evidence for that. Of course the agricultural 'revolution', and even more so our modern environment, has shown this preserved adaptation to be a profound handicap. But what is default and what is optimal? For many of us, living in the modern world with our mitochondrial and metabolic disease (pre-diabetes or worse), cutting carbs virtually entirely is both most practical and optimal, albeit not necessarily evolutionary default.

    Anyway, I love your blog. There are so few keto-friendly paleo blogs left, it would be depressing if I weren't on a ketogenic diet.

  7. Avatar
    Michael Frederik says:

    "So, at best, this theory supports ketogenic metabolism being a regular part of life in some kind of alternation with carbohydrate-based metabolism."

    Sorry, I see you sort of stated my position already. I didn't read very well! Yes, I don't buy the thrifty gene hyp. I believe most humans must have had plenty during the last several hundred thousand years, and plenty of meat and fat at that. That is, prior to agriculture. It was Cohen's "The Food Crisis in Prehistory" that made me realise that agiculture was a necessity and last resort, not an invention. An answer to overpopulation. And so in my view a relatively harmless preserved adaptation became a liability.

  8. Avatar
    mommymd says:

    Hi Amber,

    I think it's important to remember that peripheral cells can use FFA as a direct fuel via Beta oxidation. One can be a fat burner without going into ketosis.

    I do think the liver is the sensor of available fuels, supplying/controlling release of substrate and production of alternatives (ketones/lactate clearance rate/Cori cycle) dependent on changing whole body requirements.

    Plus the liver tries to protect the body against glucose toxicity (glycation). Glucose flows through it as it is absorbed, this is in contrast to lipids (chylomicrons).


  9. Avatar
    Esmée La Fleur says:

    I have done many water-only fasts over the past twenty years. My longest was 26 days. I have resorted to water-only fasting from time to time because all the foods I was eating (Vegan plant-based diet) made me feel terrible and I just could not figure out what to eat. The only time I felt good was when I ate nothing at all, and I often joked that if I did not have to eat to live everything would be fine. I came across meat-based and Ketogenic diet information here and there throughout the years, but I had a hard time letting go of my ideology about veganism, and the versions I read about always seemed prohibitively expensive for my financial resources. However, there has been an explosion of information about LCHF eating in recent years, and I feel like I am now coming full circle. Find blogs like yours, Amber, is making all the difference for me being able to pursue this type of diet. I think an all meat diet may be the answer I have been seeking about how to feel as good as I feel on a fast without actually having to fast. The benefits I experience during fasting are likely due in part to ketosis, but also to simply not putting any plant food poisons into my body. I am so eager to begin a meat-only version of the Ketogenic diet a try.

  10. Avatar
    Unknown says:

    I would have to say a low ketogenic diet foods! It is a fast way to lose some weight! I am on it and am very pleased with the results I only wanted to lose ten pounds and I lost more in about a 21/2 week period and you can definitely tell! For low carb you start out by eating 20g of carbs a day for 2 weeks. By just doing this it will shock your body and after three days you will be in a state of contoses. The state of contoses is where your body will run off the 20g of carbs and the already exsisting fat/carbs and burn them away! After 2 weeks of 20g you should go to 30g for another 2 weeks, 40g-2 weeks,50g 2 weeks.. Then drop back down to 20. It is a quick way I lost.I suggest you ketogenic diet foods through this you get more results about the ketogenic diet .

  11. Avatar
    Unknown says:

    For weight loss and strictly weight loss, there is no "American diet." The "American diet" is the one you can stick to. For some people this will be to simply eat less without changing the makeup of the foods they eat, for others it may be low carbohydrate, low fat, etc. As a rule of thumb, though, radical dietary change tends to fail because it is too hard to stick to. Portion control works for some people, as does cutting out certain types of "food" – like calorie-containing beverages or foods high in added sugar.

  12. Avatar
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