Can the human body create glucose out of fat?

Can the human body create glucose out of fat?

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I read conflicting views about whether or not the human body can create glucose out of fat. Can it?

Only about 5-6% of triglyceride (fat) can be converted to glucose in humans.

This is because triglyceride is made up of one 3-carbon glycerol molecule and three 16- or 18-carbon fatty acids. The glycerol (3/51-to-57 = 5.2-5.9%) can be converted to glucose in the liver by gluconeogenesis (after conversion to dihydroxyacetone phosphate).

The fatty acid chains, however, are oxidized to acetyl-CoA, which cannot be converted to glucose in humans. Acetyl-CoA is a source of ATP when oxidized in the tricarboxylic acid cycle, but the carbon goes to carbon dioxide. (The molecule of oxaloacetate produced in the cycle only balances the one acetyl-CoA condenses with to enter the cycle, and so cannot be tapped off to gluconeogenesis.)

So triglyceride is a poor source of glucose in starvation, and that is not its primary function. Some Acetyl-CoA is converted to ketone bodies (acetoacetate and β-hydroxybutyrate) in starvation, which can replace part - but not all - of the brain's requirement for glucose.

Plants and some bacteria can convert fatty acids to glucose because they possess the glyoxylate shunt enzymes that allow two molecules of Acetyl-CoA to be converted into malate and then oxaloacetate. This is generally lacking in mammals, although it has been reported in hibernating animals (thanks to @Roland for the last piece of info).

To be more detailed it is the irreversibly of the reaction carried by Pyruvate dehydrogenase that makes the conversion of the fatty acid chains to glucose impossible. The fatty acids chains are converted to acetyl-CoA.

Acetyl-CoA to be converted into pyruvate need an enzyme that can do the Pyruvate Dehydrogenase's inverse reaction (in humans there is no such enzyme). Than the pyruvete inside the mitochondria is converted into glucose(gluconeogenesis).

Blood Sugar Regulation

Most cells in the human body use the sugar called glucose as their major source of energy. Glucose molecules are broken down within cells in order to produce adenosine triphosphate (ATP) molecules, energy-rich molecules that power numerous cellular processes. Glucose molecules are delivered to cells by the circulating blood and therefore, to ensure a constant supply of glucose to cells, it is essential that blood glucose levels be maintained at relatively constant levels. Level constancy is accomplished primarily through negative feedback systems, which ensure that blood glucose concentration is maintained within the normal range of 70 to 110 milligrams (0.0024 to 0.0038 ounces) of glucose per deciliter (approximately one-fifth of a pint) of blood.

Negative feedback systems are processes that sense changes in the body and activate mechanisms that reverse the changes in order to restore conditions to their normal levels. Negative feedback systems are critically important in homeostasis, the maintenance of relatively constant internal conditions. Disruptions in homeostasis lead to potentially life-threatening situations. The maintenance of relatively constant blood glucose levels is essential for the health of cells and thus the health of the entire body.

Major factors that can increase blood glucose levels include glucose absorption by the small intestine (after ingesting a meal) and the production of new glucose molecules by liver cells. Major factors that can decrease blood

Energy Storage

If the body already has enough energy to support its functions, the excess glucose is stored as glycogen (the majority of which is stored in the muscle and liver). A molecule of glycogen may contain in excess of fifty thousand single glucose units and is highly branched, allowing for the rapid dissemination of glucose when it is needed to make cellular energy (Figure 3.4.2).

Figure 3.4.2: The structure of glycogen enables its rapid mobilization into free glucose to power cells.

The amount of glycogen in the body at any one time is equivalent to about 4,000 kilocalories&mdash3,000 in muscle tissue and 1,000 in the liver. Prolonged muscle use (such as exercise for longer than a few hours) can deplete the glycogen energy reserve. This is referred to as &ldquohitting the wall&rdquo or &ldquobonking&rdquo and is characterized by fatigue and a decrease in exercise performance. The weakening of muscles sets in because it takes longer to transform the chemical energy in fatty acids and proteins to usable energy than glucose. After prolonged exercise, glycogen is gone and muscles must rely more on lipids and proteins as an energy source. Athletes can increase their glycogen reserve modestly by reducing training intensity and increasing their carbohydrate intake to between 60 and 70 percent of total calories three to five days prior to an event. People who are not hardcore training and choose to run a 5-kilometer race for fun do not need to consume a big plate of pasta prior to a race since without long-term intense training the adaptation of increased muscle glycogen will not happen.

The liver, like muscle, can store glucose energy as a glycogen, but in contrast to muscle tissue it will sacrifice its stored glucose energy to other tissues in the body when blood glucose is low. Approximately one-quarter of total body glycogen content is in the liver (which is equivalent to about a four-hour supply of glucose) but this is highly dependent on activity level. The liver uses this glycogen reserve as a way to keep blood-glucose levels within a narrow range between meal times. When the liver&rsquos glycogen supply is exhausted, glucose is made from amino acids obtained from the destruction of proteins in order to maintain metabolic homeostasis.

What fat can do

Obesity researchers dream of finding ways to turn white fat into energy-burning brown fat. But white fat is pretty neat stuff, too.

Beyond playing a role in providing energy storage, white adipocytes help regulate blood sugar levels. They take up sugar, or glucose, in response to insulin secreted by the pancreas, pulling excess sugar out of the bloodstream. That's one of the big problems with excess body fat, according to the 2006 Nature paper: Too much fat throws off the glucose-regulating function of adipocytes (as does too little fat), and blood sugar levels can be thrown out of whack. [Can You Turn Fat Into Muscle?]

Adipocytes also secrete multiple proteins that influence blood sugar, according to the same paper. Some — such as leptin, adiponectin and visfatin — decrease the levels of glucose in the bloodstream. Others, such as resistin and retinol-binding protein 4, increase blood sugar.

Fatty tissue also plays a role in the immune system. Adipocytes release inflammatory compounds called cytokines, which promote inflammation. (Inflammation can be damaging when it's chronic, but it's crucially important for activating the immune cells in case of infection.) The omentum, an apron-like sheet of fat that hangs in front of the abdominal organs, is dotted with clumps of immune cells that act as hall monitors for the abdominal cavity, sampling the fluid between the organs for potential invaders, according to 2017 research.

How Sweet is it

You have probably been told more than once that eating too much sugar is not good for you. But do you know why too much sugar is bad for your body?

What’s so bad about sugar

The answer to that question is: It depends on what kind of sugar you are talking about.

Our bodies need some sugar—the kind of sugar called glucose. Glucose is a carbohydrate simple sugar and is one of the most important nutrients we feed our bodies. Glucose is found in whole wheat, vegetables, pasta, some dairy food, and honey.

Glucose helps the body break down fats and sends the signal to our brain that we are full.

NATURAL fructose found in fruits is the other simple sugar our body needs. Natural fructose gives the body some of the energy it needs to function. The fiber in fruit balances the fructose so that the fructose doesn’t have a negative effect on our bodies.

The bad sugars are dextrose, high fructose corn syrup, sucrose, white sugar (refined sugar), fructose (other than natural), and artificial sweeteners.

The reason these sugars are bad for you to include:

Most of the processing of sugar takes place in the liver. Fructose (and some of the others) can only be processed in the liver. A lot of sugar sends the liver into a panic. When this happens, the liver holds on to the sugar and stores it as fat PLUS it won’t accept messages from the brain that says we are full. This means we eat more than we need and the sugar is making more and more fat (that we don’t need).

How much sugar do you put into your body?

Studies show that the average person consumes 47 teaspoons of sugar EVERY DAY! That is like filling a 1 cup measuring cup with sugar and eating it. YUK!

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What Happens to Muscles When Glucose Is Not Available?

Glucose is to your muscles what gas is to your car -- it's the fuel that makes it go. While your body has a backup system when it comes to muscle fuel, if you're in the middle of a workout or sporting event and your muscles run out of glucose, your body may not be able to respond quick enough. This can lead to weakness and poor performance. If you think your muscles are running low on glucose often, consult a dietitian to help you design a diet that keeps them fueled.

When Does Carbohydrate Get Stored As Fat?

If carbohydrates usually get stored as glycogen, then in what situation would carbohydrates be stored as fat?

This scenario can occur when glycogen stores are fully saturated.

In this scenario, the further consumption of carbohydrates would lead to some of these carbs being converted to fatty acids. The process of converting carbohydrates into fat is known as ‘de novo lipogenesis’ (6, 7).

However, rather than being actually converted to fat, excessive carbohydrate intake usually leads to fat storage via different means.

How this fat storage occurs is explained by daily energy intake, energy expenditure, and oxidative priority.

The Oxidative Priority of Fuels and Overall Energy Intake

Oxidative priority refers to the preferential sequence in which the human body burns available fuels.

Dietary fat has the lowest oxidative priority, which means that the body will use carbohydrates and protein (and alcohol) before it oxidizes—or “burns”—dietary fat.

A high-carbohydrate diet that features excessive energy will lead to fat storage not because the carbs are turned into fat. Instead, the dietary fat itself isn’t being oxidized and is thus stored as fat (8).

In other words: since carbohydrates have oxidative priority over fat, the carbohydrates in the diet will be burned before the dietary fat.

  • Carbs get preferentially burned at the expense of dietary fat.
  • Thus, a higher intake of dietary carbohydrates slows the rate of fat oxidation.
  • In an energy surplus (excessive calorie diet), this means that not all of the dietary fat being consumed will be oxidized.
  • The unoxidized fat will be stored as body fat because carbohydrate oxidation displaced fat oxidation.

Carbohydrate Oxidation Displaces Fat Oxidation, But Energy Intake Is Key

As explained above, higher carbohydrate intake can result in more body fat being stored. However, the dietary fat portion of the diet is usually stored rather than the carbohydrate itself.

It is also important to note that this does not say anything negative about carbohydrates themselves.

Excessive intake of carbohydrates and/or fat will both lead to fat storage. Likewise, a reduced energy intake diet would mean both carbohydrates and fat can be fully oxidized, and hence the body will not store fat (9).

All in all, excessive energy intake rather than a particular macronutrient is the main driver of fat storage:

  • Excessive carbohydrate intake slows/displaces fat oxidation, leading to fat storage.
  • Excessive fat intake increases fat needing to be oxidized, leading to fat storage.


This assessment can be taken in a number of ways but more than likely you will be looking at how the humans body keeps a consistent environment in terms or physical exertion, being in an extreme environment or diet. This most likely will not be open book so it is very important that you understand this topic very well. Usually I tell my students if you can explain it to another person without referencing notes you have the level of understanding required.

The following 3 sentences must be understood before you walk into your test (:

  1. The main purpose and components of the homeostatic control system. What it does and what structures it uses and why.
  2. The mechanism of this control system, i.e. how and why it responds to the normal range of environmental fluctuations, the interaction and feedback mechanisms between parts of the system
  3. How balance is re-established following the potential effect of one specific disruption - you will not see this before the assessment. What occurs in the system to return the fluctuation back to the normal internal physiological state.
  4. For Excellence you need to explain an example of a negative feedback being broken (this is important).

Homeostasis in a general sense refers to stability, balance or equilibrium. It is the body's attempt to maintain a constant internal environment. Maintaining a stable internal environment requires constant monitoring and adjustments as conditions change. This adjusting of physiological systems within the body is called homeostatic regulation

As you can see in the picture (click on it to see a bigger version) there are a lot of systems working together. Don't stress though as you assessment will only be looking at one of these.

Homeostatic regulation involves three parts or mechanisms:

The receptor receives information that something in the environment is changing. The control center or integration center receives and processes information from the receptor. And lastly, the effector responds to the commands of the control center by either opposing or enhancing the stimulus. This is an ongoing process that continually works to restore and maintain homeostasis. For example, in regulating body temperature there are temperature receptors in the skin, which communicate information to the brain, which is the control center, and the effector is our blood vessels and sweat glands in our brain. Because the internal and external environment of the body are constantly changing and adjustments must be made continuously to stay at or near the set point, homeostasis can be thought of as a synthetic equilibrium.

From a student of Mrs Drysdale (thanks)

Overview of homeostasis in the human body homeostasis

A link to work through notes on how the body maintains homeostasis and then try the homeostasis_quiz

Animation that gives an overview of homeostasis and blood sugar levels

The hypothalamus and it's role in temperature regulation

Use this interactive animation to try to maintain homeostasis

This link gives you an overview of homeostasis and the different homeostatic systems in humans

This link is an overview of the two systems along with great diagrams and quizzes homeostatic_systems

This is a great website that overviews all of components and their interactions in thermoregulation & Blood glucose management

The homeostatic control systems in Animals have three components:

1. Some sort of receptor (sense organ) to detect a change. In the case of thermoregulation this would be skin receptors (click on image below to see the skins layers in detail.)

2. A centre of control (usually a brain or a section of the brain)

3. An effector (muscle cells, organs) to produce a response that is appropriate to the change.

These all work together in what is called a feedback system. The regulation of this is called homeostasis. This may be + or - depending on the example.

There will be a method of communication between these layers.

Here is a good video explaining the Endocrine System, and below that is a table covering all the communication pathways.

  • By far the most common found in the human body.
  • They form a looped feedback system that restores the condition to a steady state.
  • The main idea is that the stimulus from one part of the body produces a response that will stop or reduce (make smaller) the original stimulus.

Picture above is from Peter Shepard (Maurice Wilkins)

  • Rare in the human body. They form a looped system that changes the body from its original position. Normally one part of the body enhances another parts effect which can cause a escalation of the condition. This can be bad as it is not controlled that well. Some examples are human shock which can reduce blood pressure.
  • Maintaining your homeostatic environment
  • Hormone and nevous systems work together to create a homeostatic environment.

As above, your teacher will run this as an internal assessment and the standard requires the following to be covered. Each part below will link to relevant resources.

· a discussion of the significance of the control system in terms of its adaptive advantage

· an explanation of the biochemical and/or biophysical processes underpinning the mechanism (such as equilibrium reactions, changes in membrane permeability, metabolic pathways)

· an analysis of a specific example of how external and/or internal environmental influences result in a breakdown of the control system.

A control system that maintains a stable internal environment (homeostatic system) refers to those that regulate:

Humans have control systems that regulate: (possible question subjects)

body temperature (thermoregulation)

As an intro to think about thermoregualtion

Homeostasis is the control of internal body conditions so that body processes can work efficiently.

Control of body temperature is called thermoregulation.

Normal body temperature is 37ºC. This is the temperature at which enzymes work best.

The thermoregulatory centre in the brain has receptors to monitor the temperature of the blood flowing through it. Receptors in the skin send impulses to the centre about skin temperature.

If body temperature is too high:

  • Blood vessels in the skin dilate (get wider) so more blood flows to the surface of the skin.
  • Sweat is produced, which cools the body as it evaporates.

If body temperature is too low:

More water and salts, in the form of ions, are lost by sweating when it is hot. These have to be replaced by taking drinks and food.

Homeostasis of body temperature involves many types of effector systems including physiological (changes in skin blood flow, cooling mechanisms = sweating, heating mechanisms = shivering) and behavioural (sun basking, retreating to shade, changes in posture) – all controlled by the set-point of temperature sensing nerve cells in the hypothalamus (the thermometer).

Click the image below to see the larger version

The thermoregulatory centre normally maintains a set point of 37.5 ± 0.5 °C in most mammals. However the set point can be altered in special circumstances:

• Fever. Chemicals called pyrogens released by white blood cells raise the set point of the thermoregulatory centre causing the whole body temperature to increase by 2-3 °C. This helps to kill bacteria, inhibits viruses, and explains why you shiver even though you are hot.

A mild fever is an immune response to stop a bacteria based infection, although remember a fever that stays too high can damage the cell activity permanently. This link gives just a bit more information about how homeostasis works to protect the body and how sometimes a fever can be helpful.

level of blood glucose (modified from Peter Shepard's excellent PowerPoint).

One simple example of hormonal homeostatic control is the control of blood sugar level by insulin and glucagon produced by endocrine cells in the pancreas. Insulin stimulaes uptake of glucose from the blood by tissues for use or storage. This lowers blood glucose concentration. Glucagon stimulates the release of glucose from glycogen stored in the liver. This raises blood glucose concentration.Why regulate it?

  • Some tissues can use a range of energy sources such as fats and even amino acids but several important tissues in the body can only really use glucose so these tissues have a need for a constant supply of glucose to function properly. •These tissues includes red blood cells and immune cells
  • Brain and the nervous system also rely on glucose which explains why when blood glucose levels fall below about 2.5 mMthat people get seizures and can go into a coma as the brain doesn’t function properly. •Therefore maintaining a certain level of glucose is a matter of life and death.

How it gets into the cells?

  • Glucose can’t get across the membrane of cells unless specific transporters are in the membrane to provide a channel for the glucose to move through.
  • These are specific for glucose and so are called glucose transporters. They do not use energy so will only transport glucose from areas of high glucose concentration to areas of low glucose concentration (i.e down a concentration gradient). •Therefore if a cell is using glucose then levels in the cell drop and the glucose will move from the outside of the cell to the inside.•In liver cells stimulated by glucagon there will be lots of glucose produced inside the cells from glycogen therefore the flow of glucose will be from inside the cell to the outside.
  • In brain and liver there are always glucose transporters in the plasma membrane

What happens between meals?

  • Glucose levels fall and glucagon is released
  • Glucagon binds to receptors that are found on cells in the liver
  • This stimulates the release of glucose from the liver where it has been stored as long polymeric chains of glucose called glycogen.

What happens if glucose gets too low?

  • Because the brain and blood cells need glucose the body has developed emergency measures when blood glucose get dangerously low (known as a “hypo”) as might happen if a Type-1 diabetic administers to much insulin.
  • Symptoms appear (called “hypoglycemic awareness”) including fatigue, irritability, nervousness, depression, flushing, memory loss, loss of concentration, headaches, dizziness, fainting, blurring of vision, ringing in the ears, numbness, tremors, sweating and heart palpitations.
  • These are stimulated by signals from the brain that is sensing the low glucose and part of this response is to increase adrenaline levels in an attempt to increase blood glucose levels
  • The warning signs are very useful for a Type-1 diabetic as the hypoglycemia can easily be overcome by taking in some glucose.
  • Unfortunately the ability to detect hypoglycemia sometimes get lost by diabetics (a condition termed “hypoglycemic unawareness”).

After a meal?

  • Glucose levels rise and insulin is released
  • Insulin binds to receptors that are found on cells in the liver, in muscle and in fat cells
  • This stimulates the uptake of glucose into these tissues so blood glucose levels go down
  • Glucose taken up by liver is mostly stored as glycogen
  • Some of the glucose going into fat cells contribute to the accumulation of fat in these cells

What happens when insulin binds to its receptor?

  • Insulin moves through the blood stream until it finds its specific receptor on the surface of the liver cells, muscle cells and fat cells.
  • The receptor is a protein that spans the membrane
  • The binding of insulin causes an allosterically induced change in the shape of the intracellular portion of the receptor which activates an enzymatic activity.
  • The receptor is now said to be activated and as shown in later slides this brings about changes inside the cell.
  • This is in effect allowing the hormone on the outside of the cell to regulate functions inside the cell even though the hormone has not entered the cell. This is called “transduction” and the whole process is often called signal transduction.

Work thorough the following animation here

The biological ideas related to the control system includes the:

  • purpose of the system
  • components of the system
  • mechanism of the system (how it responds to the normal range of environmental fluctuations, interaction and feedback mechanisms between parts of the system)
  • potential effect of disruption to the system by internal or external influences.

Environmental influences that result in a breakdown of the control system may be external influences such as extreme environment conditions, disease or infection, drugs or toxins, or internal influences such as genetic conditions or metabolic disorders.

At all stages of the life of a mammal the cells of the body are provided with a constant supply of the things they need.

There is a buffering of the fluctuation of the environment so that the cells in a mammal may live even though the conditions outside the body are not good.

A control system (i.e. a homeostatic system) that maintains a stable internal environment refers to those that regulate one of:

  1. body temperature
  2. blood pressure
  3. osmotic balance
  4. level of blood glucose
  5. levels and balance of respiratory gases in tissues.

Because the cells have a fluid bathing them whose chemical composition and temperature is VERY CONSTANT these cells are able to function equally well in the tropics or the arctic, in the ocean, in fresh water or in the desert.

Environmental influences that result in a breakdown of the control system may be:

  1. external influences such as extreme environment conditions, disease or infection, drugs or toxins
  2. internal influences such as genetic conditions or metabolic disorders.

HOMEOSTASIS = maintenance of constancy of the INTERNAL ENVIRONMENT

where the `internal environment' = the INTERCELLULAR FLUID (the medium in which body cells are bathed) - also known as INTERSTITIAL or TISSUE FLUID.


1. Whenever a condition (e.g.. temp glucose level in blood etc.) deviate from a set point or NORM (e.g.. 37 C 90mg glucose per 100cm blood) the corrective mechanism is triggered by the very entity which is to be regulated, ie. homeostasis involves a self-adjusting mechanism of the control process being built into the system.

2. In the case of e.g.. glucose regulation an increase in the amount of glucose triggers a process to decrease it. Conversely, a decrease in the glucose level triggers a process to increase it. In both cases the result is a reasonably constant level of glucose. When a change in an entity brings about the OPPOSITE EFFECT this is known as a NEGATIVE FEEDBACK mechanism.

Sometimes the corrective mechanism leading to NEGATIVE feedback breaks down with the result that a deviation from the norm initiates FURTHER deviation. This is known as POSITIVE FEEDBACK.

e.g.. Once the temperature regulating mechanisms fail ,the metabolic rate goes on climbing even if the environmental temp. is no longer increased. This is because every time the metabolic rate increases it generates more heat which increases the metabolic rate a bit more, and so on.

It is difficult to think of any household situation in which positive feedback systems operate. When a baby is born, contractions of the womb become progressively stronger as the head is pressed down into the vagina (birth canal) this is a positive feedback system that results in the expulsion of the baby from the mother's womb.

Another physiological example can be seen in the generatic of a nerve impulse where Na+ (sodium ions) crossing the nerve cell membranes stimulate further Na+ to cross. (see later) This process only lasts for a brief moment.

It is clear from the examples of POSITIVE FEEDBACK (above) that (i) under normal conditions it is UNCOMMON since (ii) the end result is a further increase or further decrease in the entity concerned and hence CONSTANCY IS AVOIDED.

3. Homeostasis must necessarily involve FLUCTUATIONS, small though these may be.

Only by deviating form the NORM can the mechanism be brought into play.

4. The feedback system must have:

· RECEPTORS (or SENSORS) capable of detecting the change

· a CONTROL MECHANISM (or MONITOR) capable of initiating the appropriate corrective measure

· EFFECTORS which can carry out these corrective measures.

As a simplified example, consider the movement of fluid through a pump - to make this a physiological system, assume that the fluid is blood and the pump is a heart. The function to be controlled homeostatically is the rate of outflow of blood from the heart, so this is the output and there must be a sensor that measures the rate of outflow. This sensor transmits its measurements to the monitor, which compares the actual with the required output the monitor sends signals to the pump - the heart muscle - and so adjusts the rate of pumping when the output is different from the set level.

Dear Mark: How Much Glucose Does Your Brain Really Need?

We now know that the oft-repeated “your brain only runs on glucose!” is wrong. I’ve mentioned it before, and anyone who’s taken the time to get fat-adapted on a low-carb Primal eating plan intuitively knows that your brain doesn’t need piles of glucose to work, because, well, they’re using their brain to read this sentence. Obviously, you eventually adapt and find you have sufficient (if not much improved) cognition without all those carbs. That said, some glucose is required, and that’s where people get tripped up. “Glucose is required” sounds an awful lot like “your brain only uses glucose” which usually leads to “you need lots of carbs to provide that glucose.” And that’s the question today’s edition of “Dear Mark” finds itself attempting to answer: how much glucose is required?

Hi Mark,

I have a little problem. Even though I’m able to function at work, maintain conversations, and go about my daily life without having segments of my brain suddenly stop working while eating Primal, my friends are worried about my brain. All they know is that the brain needs glucose. What can I tell them? How much glucose does my brain actually require to keep working?



I wouldn’t be too hard on your friends. They mean well and it’s a common misconception. Instead of chiding them, rubbing their faces in the knowledge that you can function quite adequately on a high-fat diet, educate them.

How much glucose the brain requires depends on the context. There’s not one single answer.

If you’re on a very high fat, very low carb diet – like a traditional Inuit diet – your brain will eventually be able to use fat-derived ketones for about 50-75% of its energy requirements. Most ketones are produced in the liver, but astrocytes in the brain also generate ketones themselves for use by neurons. You think we’d have that kind of set up in our brains if ketones weren’t useful to have around? If all we could do was burn glucose up there, what would be the point of even having localized ketone factories? Anyway, since the brain can use about 120 grams of glucose a day (PDF), that means you’d still need at least 30 grams of glucose while running on max ketones.

If you’re involved in strenuous exercise, your brain will be running primarily on lactate. Yep, lactate – that unwanted metabolic byproduct of muscle metabolism. During exercise, when the muscles are using up most of the available glucose to lift things and move a bunch of intelligent primate flesh through three dimensional space, and where inadequate oxygen (hence breathing hard) leads to incomplete glucose and pyruvate breakdown and increased lactate levels, the brain will draw upon lactate as a direct energy source. Not only that, but lactate appeared to make the brain run more efficiently, more snappily, and when both are available, the brain prefers lactate over glucose. Other research has found that the brain also prefers lactate in the hours and days immediately following a traumatic brain injury. I’m not sure how much glucose the brain requires when it’s accessing lactate, but it’s definitely fewer than 120 grams.

Of course, even when you need some glucose, that glucose needn’t necessarily come from dietary carbohydrate. It can famously come from gluconeogenesis, the process by which the liver converts amino acids into glucose. It can also come from glycerol, a byproduct of fat metabolism. In deep fasting situations, glycerol can contribute up to 21.6% of glucose production, with the rest presumably coming from gluconeogenesis. The glycerol can come from both dietary fat and adipose tissue (the authors of that glycerol fasting study even suggest that fasting burns body fat in order to provide glycerol for glucose production), while the amino acids can come from dietary protein (if you’re eating) or muscle (if you’re starving).

Overall, recent research into the metabolic demands of brain slices (“living” pieces of brains isolated and used for research) shows that incorporating other energy substrates – ketones, lactate, or even pyruvate – into the glucose solution improves oxidative metabolism and neuronal efficiency. Before you say “but this was in vitro, my brain’s not sliced up and submerged in a weird syrupy solution,” know that the whole point of the study was to better replicate the conditions of the kind of real, actual, living, thinking brains we find in human heads. The authors note that the glucose-only solution normally used to fuel brain slices in other studies is limited, because “in the intact brain, complex machinery exists that coordinates energy substrates delivery and adjusts energy substrate pool composition to the needs of neuronal energy metabolism.” In other words, glucose solution is an easy, dependable way to fuel brain slices, but it’s an incomplete representation of how brains work in heads. The authors conclude that “in slices as well as in vivo, the ability of glucose to maintain energy metabolism is limited and neuronal energy supply should be supported by other oxidative substrates.”

So, a healthy, efficient brain is one that draws on several different fuels. A healthy, efficient brain is one that uses ketones (and perhaps lactate and other fuels) to spare some glucose. A complete reliance on glucose indicates an underachieving brain, a brain that could do so much better, a brain that could really use a coconut milk curry and some intense exercise every now and again. As far as we can tell, then, the absolute physiological minimum is 30 grams of glucose. I wish I could provide hard numbers for some of the other contexts beyond near carnivory (like basic 150 grams carbs Primal eating with coconut or maybe figuring out how to rely on lactate fueling), but the numbers don’t really matter in practice. What matters is that our brains don’t need the full 120 grams of glucose, especially if we’re following a Primal Blueprint eating plan.

Questions? Comments? Concerns? Leave them here. Thanks for reading!

The all-out, 6-minute stationary bike workout

  • 2 minutes — Warm up, pedaling at an easy pace.
  • 20 seconds — Pedal as fast and hard as you can while maintaining control and good form. Don’t hold anything back. At the end, you should be huffing and puffing to catch your breath.
  • 90 seconds — Recovery movement. Slow to a very easy pace. Don’t stop. Keep pedaling slowly until your breathing returns to a comfortable rate. As you near the 90-second mark, start to ramp up your intensity again.
  • 20 seconds — High-intensity exercise.
  • 90 seconds — Recovery pace.
  • 20 seconds — High-intensity exercise.

That’s 6 minutes. You’re done!

For access to exclusive gear videos, celebrity interviews, and more, subscribe on YouTube!

NIH study shows how insulin stimulates fat cells to take in glucose

Findings could aid in understanding diabetes, related conditions.

Using high-resolution microscopy, researchers at the National Institutes of Health have shown how insulin prompts fat cells to take in glucose in a rat model. The findings were reported in the Sept. 8 issue of the journal Cell Metabolism.

By studying the surface of healthy, live fat cells in rats, researchers were able to understand the process by which cells take in glucose. Next, they plan to observe the fat cells of people with varying degrees of insulin sensitivity, including insulin resistance — considered a precursor to type 2 diabetes ( These observations may help identify the interval when someone becomes at risk for developing diabetes.

"What we're doing here is actually trying to understand how glucose transporter proteins called GLUT4 work in normal, insulin-sensitive cells," said Karin G. Stenkula, Ph.D., a researcher at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and a lead author of the paper. "With an understanding of how these transporters in fat cells respond to insulin, we could detect the differences between an insulin-sensitive cell and an insulin-resistant cell, to learn how the response becomes impaired. We hope to identify when a person becomes pre-diabetic, before they go on to develop diabetes."

Glucose, a simple sugar, provides energy for cell functions. After food is digested, glucose is released into the bloodstream. In response, the pancreas secretes insulin, which directs the muscle and fat cells to take in glucose. Cells obtain energy from glucose or convert it to fat for long-term storage.

Like a key fits into a lock, insulin binds to receptors on the cell's surface, causing GLUT4 molecules to come to the cell's surface. As their name implies, glucose transporter proteins act as vehicles to ferry glucose inside the cell.

To get detailed images of how GLUT4 is transported and moves through the cell membrane, the researchers used high-resolution imaging to observe GLUT4 that had been tagged with a fluorescent dye.

The researchers then observed fat cells suspended in a neutral liquid and later soaked the cells in an insulin solution, to determine the activity of GLUT4 in the absence of insulin and in its presence.

In the neutral liquid, the researchers found that individual molecules of GLUT4 as well as GLUT4 clusters were distributed across the cell membrane in equal numbers. Inside the cell, GLUT4 was contained in balloon-like structures known as vesicles. The vesicles transported GLUT4 to the cell membrane and merged with the membrane, a process known as fusion.

After fusion, the individual molecules of GLUT4 are the first to enter the cell membrane, moving at a continuous but relatively infrequent rate. The researchers termed this process fusion with release.

When exposed to insulin, however, the rate of total GLUT4 entry into the cell membrane peaked, quadrupling within three minutes. The researchers saw a dramatic rise in fusion with release — 60 times more often on cells exposed to insulin than on cells not exposed to insulin.

After exposure to insulin, a complex sequence occurred, with GLUT4 shifting from clusters to individual GLUT4 molecules. Based on the total amount of glucose the cells took in, the researchers deduced that glucose was taken into the cell by individual GLUT4 molecules as well as by clustered GLUT4. The researchers also noted that after four minutes, entry of GLUT4 into the cell membrane started to decrease, dropping to levels observed in the neutral liquid in 10 to 15 minutes.

"The magnitude of this change shows just how important the regulation of this process is for the survival of the cell and for the normal function of the whole body," said Joshua Zimmerberg, Ph.D., M.D., the paper's senior author and director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program in Physical Biology.

The research team next plans to examine the activity of glucose transporters in human fat cells, Zimmerberg said. "Understanding how insulin prepares the cell for glucose uptake may lead to ideas for stimulating this activity when the cells become resistant to insulin."