Ketones


Ketones are a beneficial product of fat metabolism in the body. When carbohydrate intake is restricted, it lowers blood sugar and insulin levels. As insulin is lowered, the body can access stored fat from the fat cells and send it into the bloodstream. These fatty acids flow to the liver where they are metabolized in liver cell mitochondria in a process called beta-oxidation.  As the amounts of fatty acids being metabolized increases, a molecule called acetyl-CoA starts to build up and this molecule is shunted into a process called ketogenesis. Ketogenesis results in the creation of ketone bodies, which are then sent out into the blood stream (as interestingly, the liver cells can't use ketones). As blood levels of ketones rise above 0.5 mM, the skeletal and cardiac muscles and eventually the brain take up the ketones, break them back down into acetoacetate and then back to Acetyl-CoA and metabolizes them in the cellular respiration process.

There are three major types of ketone bodies present in the human blood stream when the metabolic process of ketosis is dominant:

  1. Acetoacetate (AcAc) is created first
  2. β-hydroxybutyrate (BHB) is created from acetoacetate
  3. Acetone is a spontaneously created side product of acetoacetate

In times of starvation, or a low carbohydrate intake resulting in low insulin levels, ketone bodies supply up to 50% of the energy requirements for most body tissues, and up to 70% of the energy required by the brain.

Glucose is the main source of fuel for neurons when the diet is high in carbohydrates. But when carbs are restricted, these fatty acid fragments are used preferentially by brain cells.

During fasting or low carbohydrate intake, levels of ketone bodies in the blood stream can rise to levels between 0.5mM and 5 mM, depending on the amount of protein and carbohydrates consumed.  This state is called nutritional ketosis.

In contrast, Type 1 diabetics who don't inject enough insulin, or Type 2 diabetics whose pancreatic output of insulin is very low, may experience diabetic ketoacidosis.

Ketoacidosis is a wildly out of control ketotic state in which blood levels of ketone bodies may rise above 10-25mM.  This type of metabolic derangement happens because there is no insulin to put the brakes on fat burning, and this results in a flood of fatty acids flowing out of fat cells, which are then converted to ketone bodies in the liver and dumped into the blood stream. These much higher levels of ketone bodies result in the blood pH becoming too acidic and causing the health issues associated with ketoacidosis.


Measuring Ketones

After a few weeks of adapting to a ketogenic diet, most people's blood ketone levels go above the 1 mM level. As the levels of ketone bodies rise, the brain begins to use more than half of them for fuel.

In addition, the muscles of the body use all of the ketone body types. But after a few weeks of keto-adaptation, the muscles start converting the acetoacetate into β-hydroxybutyrate (BhoB) and returning it to circulation.  Although BoHB is the more stable molecule, when it is taken up by muscle tissues, it has to be converted back to acetoacetate so that cells can metabolize it.  The conversion between BHoB and Acetoacetate goes back and forth depending on where in the metabolism it is being used.  The third type of ketone, acetone is very volatile and released in the breath and urine.  However it also has some effects on brain signaling and it prevents neuron hyperexcitability, which may explain why being in ketosis can calm neurological conditions such as epilepsy.

So as time goes on and more acetoacetate is converted, the levels of β-hydroxybutyrate ketones increase, and the acetoacetate levels decrease.  This is important to know because the urine Ketone test strips that you buy in the drugstore only test for acetoacetate, not β-hydroxybutyrate ketones.

So the longer you are eating low carb, the less MEASURABLE ketone bodies will show up in your urine and on the Ketostix. In other words, it will seem like ketosis is slowing. However, at this point, your brain will be happily burning the β-hydroxybutyrate ketones for fuel, and as long as you stay under your carb sensitivity levels, you will be burning stored fat as your main energy source.

The good news is that just recently, several companies have developed a blood meter to check for blood levels of BHoB at home. I've included links to these new products in the side bar at right.


Staying in Ketosis

For most people, eating more than 100 grams of protein along with more than 60-100 grams of carbohydrate on a daily basis will stop the process of ketogenesis and halt nutritional ketosis.  Blood levels of ketone bodies will fall below levels which can be used efficiently by the brain.

This is because protein in excess of body requirements is metabolized into glucose in the blood stream. About 56% of excess protein is metabolized into glucose, and this impacts ketosis as well.

For others who are super sensitive to carbohydrate, eating  more than 20 carbs and 80 grams of protein per day may interfere with ketosis as well.

Here's a great video of Dr. Peter Attia talking about his experience with manipulating nutritional ketosis and his ketone levels.  It's long but very informative, especially as the effect of exercise on ketosis.


For more information about the chemical process of ketogenesis, this website is useful.

Much of the information for this page was adapted from the book The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-Saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable by Dr. Jeff Volek and Dr. Stephen Phinney. I highly recommend buying and reading it.

Done with Ketones, back to Ketosis

How Do I Check for Ketosis?

If you have started a ketogenic diet and want to be able to check your ketone levels, there are several ways to do this.

You can buy ketone stix, and check the levels of ketones in your urine. This method has been the most common method for years, but recently, several companies have developed a blood ketone meter for home use.

This method of checking ketones in the blood is much more accurate, but is also much more expensive. Jimmy Moore has a nice post on using the blood meters here.

Below are links to the Keto-Stix for urine checks, and the various brands of ketone meters for blood checks.

If you would like to read more, Jeff Volek and Steve Phinney discuss the new method of checking blood ketones in their book "The Art and Science of Low Carbohydrate Performance".

and this Volek and Phinney book is a good introduction the science of ketogenic diets.