Can someone very generally describe how the brain consumes ketoacids/ketone bodies when blood glucose has been completely depleted?


2 Answers 2


Human body is a glucose driven machine which intake carbohydrates and converts to glucose. Energy is yielded from the glucose and glucose is stored as glycogen. When the carbohydrate intake is somehow reduced then body will shift its mechanism and uses the fatty acids to produce energy. Liver synthesis ketones from fatty acids in our diet or from body fat. Ketones(acetoacetate and acetone) are released into the blood, which is absorbed by the brain and synthesis energy from it through their mitochondria.

The brain gets a portion of its energy from ketone bodies when glucose is less available (e.g., during fasting, strenuous exercise, low carbohydrate, ketogenic diet and in neonates). In the event of low blood glucose, most other tissues have additional energy sources besides ketone bodies (such as fatty acids), but the brain has an obligatory requirement for some glucose. After the diet has been changed to lower blood glucose for 3 days, the brain gets 25% of its energy from ketone bodies.After about 4 days, this goes up to 70% (during the initial stages the brain does not burn ketones, since they are an important substrate for lipid synthesis in the brain). Furthermore, ketones produced from omega-3 fatty acids may reduce cognitive deterioration in old age. Reference

When the body starts using the fatty acids for energy production, one problem arises in the brain and that is the blood-brain barrier( barrier that separates the circulating blood from the brain extracellular fluid in the central nervous system )Brain cannot use long chain fatty acids because they cannot cross the blood-brain barrier due to their bondage with albumin. As ketones are medium chain fatty acids which can effectively cross the barrier. So brain uses the ketones for energy production by a process called as ketosis. The ketone bodies are then incorporated into acetyl-CoA and used in the citric acid cycle.

The citric acid cycle – also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle – is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetate derived from carbohydrates, fats and proteins into carbon dioxide and chemical energy in the form of adenosine triphosphate (ATP). Reference

Metabolic pathways to produce energy

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  • $\begingroup$ I've linked to your answer in this question. $\endgroup$
    – uhoh
    Commented Jun 11, 2017 at 5:50

Actually there is fatty acid transport through the BBB. Maybe the rate of this transport is not enough, I don't know, I think it does not really matter.

What really happens here, that the liver prepares the fatty acids, so the brain can use them more easily in the form of ketoacids to produce energy.

fatty acid catabolism shared between the liver and the brain

  • fatty acid catabolism shared between the liver and the brain - ref
  • $\begingroup$ What you tell is astonishing: you learn about fatty acids being prohibited from being turned into glucose. With this that doesn't seem to be true: fatty acids to Acetyl-CoA and then clockwise through the TCA cycle, left hand, to Oxaloacetate, then pyruvate, then: glucose. It looks as if it is a matter of plentitude of carbon to burn, as by being shuffled through the TCA cycle CO2 two times is being set free. - Should be written in all the textbooks! $\endgroup$ Commented Feb 17, 2022 at 17:45
  • $\begingroup$ @PeterBernhard Yes, in the human body there is no fatty acid -> carbohydrate biochemical pathway or it is very slow (note that this is not true for all animals). Same is true for fructose and ethanol, that's why they cause oxidative stress, fatty liver and diabetes. I think many times you can prevent diabetes by avoiding fructose (pratically most of the sweet foods and drinks) and alcohol. I think this information about carbs and fatty acids is already in textbooks, at least I learned it in the university 10+ years ago. The fructose part is a lot more recent. $\endgroup$
    – inf3rno
    Commented Feb 18, 2022 at 2:50
  • $\begingroup$ Pun on "prohibition"? I mean alcohol and fructose sound icy to me, take my excuses for my strange English, by the way; the graphic has a link but the ref does not tell about which book that the graphic is from. As it occurs to me...even in wording that question could have been me. Maybe my comment truly tells - not the whole "stuory fur" sure, as you mention fructose - so how does prohibition of fructose from being turned to sweet work? Can you e-"leber"ate? $\endgroup$ Commented Feb 23, 2022 at 21:23
  • $\begingroup$ @PeterBernhard Last time I read about fructose, it was something new and very logical. Now according to new reviews it is not as certain as it was. mdpi.com/2072-6643/9/2/96/htm mdpi.com/2072-6643/9/9/981 sciencedirect.com/science/article/abs/pii/S0168827818300667 academic.oup.com/ajcn/article/100/3/833/4576481?login=false scholar.google.hu/… $\endgroup$
    – inf3rno
    Commented Feb 23, 2022 at 23:23
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    $\begingroup$ Again, thank you for clarifying what maybe is some common non having understood: e.g. medscape.com: "High levels of acetoacetate in blood may result from the following: Diabetic ketoacidosis and alcoholic ketoacidosis". As for me, I needed advice on that being the other dark side of the medal (no German) of ketose being needed. So, your shed new light on some, literally, half-knowledge. Diabetes, alcohol seem to imitate the need that must be: of calories, to starve is exhilarating. To sum up: with your answer "ketoacidose" becomes understood, it's good, not bad, it's regular. $\endgroup$ Commented Feb 24, 2022 at 6:14

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