Ketosis: Metabolic Flexibility in Action

Ketosis is an energy state that your body uses to provide an alternative fuel when glucose availability is low.  It happens to all humans when fasting or when carbohydrate intake is lowered.  The process of creating ketones is a normal metabolic alternative designed to keep us alive if we go without food for long periods of time. Eating a diet low in carb and higher in fat enhances this process without the gnawing hunger of fasting.

Let’s talk about why ketones are better than glucose for most cellular fuel needs.

Body Fuel Basics

Butterfat for Ketosis

Normal body cells are able to create energy by using the food we eat and the oxygen we inhale to complete normal cellular “respiration” and make ATP (adenosine triphosphate), our main cellular energy source. Most of this energy production happens in the mitochondria, tiny organelles which act as cell fueling stations. There are two primary types of food-based fuel that our cells can use to produce energy:

  • The first cellular fuel is glucose, which is commonly known as blood sugar. Glucose is a product of the starches and sugars (carbohydrates) in our diet. This fuel system is necessary, but it has a limitation.  The human body can only store about 1000-1600 calories this way. The amounts stored depend on how much muscle mass is available.  Men will be able to store more because they have larger muscles.  Since most people use up about 2000 calories a day just being and doing normal stuff, you can see that if food weren’t available for more than a day, the body would run out of energy. Not good for continuing life.
  • The second type of cellular fuel are ketone bodies, which come from the breakdown of fatty acids. These come from fats we eat or from the metabolism of stored fat from our fat cells.  The human body can store hundreds of thousands of calories in the form of fat, so we could say that this system of energy is almost unlimited, depending on how long one goes without food.  Eventually, it would get used up, but people have been known to fast for months and live through it.

When glucose levels are low, especially over time, most cells will switch to using ketone bodies for fuel. Ketones allow cells to be metabolically flexible, so to speak. Even the brain and nerve cells, which are heavily dependent on glucose can utilize ketone bodies for fuel. This ability of most normal cells to use ketones when glucose is unavailable indicates that their cellular mitochondria are healthy and functioning properly. 

In addition, ketones have some unique properties which make them a “cleaner” fuel for your cells to use.  Burning fat for fuel causes less oxidative damage (think “free radicals”) to the cell, and actually makes it possible for the cell to create much more energy than it can from glucose.

Ketosis and Ketones To the Rescue

So how does our body make ketones out of the stored fat?  When stored fat (in the form of triglyceride) is called upon to be metabolized for fuel, a substance called hormone sensitive lipase (HSL) breaks the triglyceride compound down into one glycerol molecule and 3 fatty acid molecules. These fatty acid molecules come in various lengths of carbon based chains.

The fatty acids then flow into either liver or muscle cells and are transported into the mitochondria of the cell to be metabolized carbon by carbon in a process called beta-oxidation. As glucose levels fall and fatty acid levels in the blood rise, the liver cells ramp up beta-oxidation which increases the amounts of a molecule called Acetyl-CoA. As the level of Acetyl-CoA rises, it is shunted to a process called ketogenesis. Ketogenesis generates a ketone body called acetoacetate first, and this ketone is then converted into the two other types of ketones: beta-hydroxybutyrate, and acetone.  Meanwhile, the glycerol part of the fat molecule gets converted into glucose in a process called gluconeogenesis, which means "make new sugar".

As ketones levels rise in the body, the cells of heart, brain and muscles can use them for fuel. And once the body is using ketones as a main fuel source, there are some profound and positive health effects.  Ketogenic diets are very effective for correcting cellular metabolic dysfunction. The high blood sugar of diabetes gets reversed, the seizures of epilepsy can be calmed, Alzheimers and Parkinsons symptoms are alleviated, extra weight can be lost, joint pain is diminished and so on.  In other words, the ketogenic diet is not a “fad.” It is a potent regulator of metabolic derangement, and when formulated and implemented correctly, it can be extremely effective at reversing all kinds of health problems. (See this paper.)

Carbohydrates are Not Essential, But..

Although ketones are beneficial, the body must still have some glucose, mostly for the brain and red blood cells.  If a person goes without food for a long period of time, the body will breakdown fat and muscle to create glucose for the brain, because without some glucose, the brain will die and take you with it.
This brain glucose need is the main reason that registered dietitians insist on keeping alive the myth that carbohydrates are essential nutrients (meaning we have to eat them or we will die). This is incorrect, biochemically speaking. RDs teaching that carbs are essential neglect to take into account that the brain can use ketones for over half of its fuel requirements once carbohydrate intake is lowered and ketone production ramps up. The process of gluconeogenesis can make all the glucose the brain needs, once the body is keto-adapted (good at burning ketones for fuel). So although glucose is essential for the brain, eating carbohydrates to make glucose is NOT essential, especially if you are in ketosis.

Most Diet Researchers Don't Get Ketogenic Diets

The thing to remember about ketosis is that it takes a few weeks for the body to become "keto-adapted*" and switch to burning ketones for fuel once carbohydrate consumption is lowered. 
Also, carbohydrate intake levels have to be lowered enough (below 60 grams per day or lower depending on insulin resistance levels) for ketone bodies to be made at a level that the brain can use. If you only lower carbohydrate intake a little, then the ketotic process gets short circuited, and can't do its job of taking over as a fuel source.
Most unfavorable low carb studies which reported the "unhealthy effects" of a low carb diet were actually poorly designed, in that they weren't long enough to account for the "keto-adaptation" period, and they didn't cut carbohydrate intake low enough to ramp up ketosis to the protective amounts needed by the brain.

*Keto-adapted is a term coined by Jeff Volek and Stephen Phinney in their excellent book "The Art and Science of Low Carbohydrate Living."

My Doctor Told Me Ketosis is Dangerous.  Is That True?

Some people, including doctors, get the dangerous condition of ketoacidosis confused with normal benign dietary ketosis but they are different conditions.
Normal nutritional ketosis is NOT dangerous. Every person alive goes into mild ketosis each time they go without eating for 6-8 hours. The effects of ketosis vary with individual experience but ketones in normal amounts are not dangerous.
Unless you are a Type 1 diabetic (meaning your pancreas makes no insulin at all) or a Type 2 diabetic with a really burned out pancreas, ketosis is kept in check by the presence of insulin in the body. Insulin regulates the flow of fatty acids from our fat cells. As long as insulin is circulating within the body, in general, the flow of fatty acids and the production of ketone bodies is highly regulated and limited to a range that is not dangerous.
In fact, ketosis and ketone bodies are actually quite beneficial to the body. In this paper, research scientist Richard Veech (who does understand ketosis) writes:

"Surprisingly, D-beta-hydroxybutyrate...may also provide a more efficient source of energy for brain per unit oxygen, supported by the same phenomenon noted in the isolated working perfused rat heart and in sperm. It has also been shown to decrease cell death in two human neuronal cultures, one a model of Alzheimer's and the other of Parkinson's disease. These observations raise the possibility that a number of neurologic disorders, genetic and acquired, might benefit by ketosis."

This 2013 paper talks about the benefits of ketosis for many varied health conditions. The abstract states:

"Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician’s hand."

And these papers also describe the benefits of ketosis here, here and here. Also, just recently, Dr. Jeff Volek and Dr. Steve Phinney did a great interview on nutritional ketosis. It's long but worth watching.

And here's another great video of Dr. Jeff Volek speaking on keto-adaption.

Done with Ketosis, back to Home

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.