Ketones: The Fourth Fuel

STORY AT-A-GLANCE

• Your body can use four types of fuel: carbohydrates, fats, proteins and ketones. Of these, ketones burn the cleanest. They create far fewer harmful free radicals when burned and do not rely on insulin

• When you're generating ketones and your blood ketone levels go up, the ketone enters the cell through a monocarboxylic acid transport protein. Even without a rise in insulin, the cells are efficiently fueled

• With today's standard American diet, most people never reach a state of fat burning and ketosis. They’re constantly feeding their bodies carbohydrates, and in this high-insulin state, they simply cannot burn fat. Over time, it wears out your metabolic machinery, resulting in insulin resistance and weight gain

• Nutritional ketosis is a powerful way to improve your body’s natural antioxidant capacity

• Optimizing your metabolic health appears to be an effective way to mitigate the severity of a COVID-19 infection. The reason for this is because when you're metabolically flexible, you're not insulin resistant, and insulin resistance is a significant risk factor

Travis Christofferson has written three books on metabolic health optimization. His third one was "Ketones, The Fourth Fuel: Warburg to Krebs to Veech, the 250 Year Journey to Find the Fountain of Youth."

Interestingly, optimizing your metabolic health appears to be an effective way to mitigate the severity of a COVID-19 infection. The reason for this is because when you're metabolically flexible, you're not insulin resistant, and insulin resistance and diabetes are significant risk factors.

The ketogenic diet was a standard of care in the 1920s for pediatric epilepsy, but once antiseizure drugs came out in the '30s, it was shelved and eventually forgotten. Fasting encountered the same fate. As noted by Christofferson, therapeutic fasting was huge in the '60s, yet the benefits of this strategy eventually fell by the wayside of medical history as the low-fat movement took hold.

Today, as we face epidemic levels of insulin resistance and its associated health effects, including diabetes, heart disease and increased vulnerability to viral infections, nutritional ketosis could not be more pertinent.

The Four Fuels

The four fuels are carbohydrates, fats, proteins and ketones. Carbs and fats are the two primary ones. Proteins are primarily used as building blocks, but they can also be broken down and be burned as fuel. They just cannot be stored for anything other than emergency starvation fuel.

Protein can also be converted back into glucose through gluconeogenic pathways. When you fast, protein can be used as an alternative fuel, but the ideal fuel is ketones. Christofferson explains the metabolic difference between carbohydrates, fats and ketones as follows:

High-Carb Diets Damage Your Metabolic Machinery

The problem is that with today's standard American diet, most people never reach this state of fat burning and ketosis. They're constantly feeding their bodies carbohydrates, and in this high-insulin state, they simply cannot burn fat. Over time, it wears out your metabolic machinery, resulting in insulin resistance and weight gain.

As explained by Christofferson, glucose is a very rigid planar molecule, and when in your blood, it damages your epithelial cells, nerves and just about everything else. For this reason, your body has to get rid of it quickly. The insulin tells your cells to take up the glucose to lower the glucose level in your blood.

It then tells the cells to process it by turning on the last step of glycolysis, the pyruvate dehydrogenase complex, so that the glucose can be processed. When those two "machineries" wear out, you develop insulin resistance. What this means is your cells no longer respond well to insulin, and as a consequence your blood glucose remains elevated.

You're also burning less fuel, which diminishes all metabolic processes. This is in context to a state of insulin resistance: Less glucose is able to enter the Krebs cycle and ATP production slows. For example, the efficiency by which your body makes antioxidants and neurotransmitters decreases. The beautiful thing about ketone metabolism is it completely bypasses all this pathology. It doesn't depend on insulin pathways.

So, when you're generating ketones and your blood ketone levels go up, the ketone enters the cell through a model carboxylic acid transport protein. Even without a rise in insulin, the cells are efficiently fueled.

Ketones also do not need pyruvate dehydrogenase complex. Instead, ketones go directly into the Krebs cycle. So, all of a sudden, diminished metabolic pathways spring back to life and you're able to generate energy, antioxidants and all the rest. Your brain also gets the fuel it needs for optimal function.

Metabolic Benefits of Ketones

Ketones have a number of specific benefits. For starters, they're thermodynamically and metabolically efficient, meaning they burn cleaner than glucose, thus creating far less free radical damage and inflammation in your body. Christofferson explains:

Ketosis Dramatically Improves Antioxidant Production

The concept of NADPH is profoundly important and not widely appreciated. It's probably every bit as important as NAD+, especially with respect to recharging endogenous intracellular antioxidants. As explained by Christofferson, the only thing that determines the antioxidant status of a cell is the redox ratio of NADPH, and the only known way to change that redox ratio is through burning beta-hydroxybutyrate.

There's a pervasive belief that you can diminish free radicals simply by consuming antioxidants, but that has never actually been proven. As noted by Christofferson:

Radiation and Antiaging Benefits

Christofferson cites research showing that when you give mice ketone esters after dosing them with radiation, the chromosomal damage incurred is reduced by 50%, compared to mice fed a normal carbohydrate diet. He believes taking ketone esters is therefore advisable when getting X-rays or when flying, for example. Ketone esters may also help counteract the normal ravages of aging.

Beta-hydroxybutyrate also activates FOXO3a, which is perhaps one of the most important pathways for antiaging. FOXO3a in turn changes the expression of hundreds of other genes.

Some of those genes regulate internal antioxidant production such as catalase and superoxide dismutase. These are not like traditional antioxidants that have to be recycled by NADPH. They operate by traditional ketolysis, where superoxide is changed into hydrogen peroxide and then water.

Ketone Esters Improve Athletic Performance

Christofferson also reviews how ketone esters can improve athletic performance and recovery:

Other Benefits of Ketone Esters

There's also some data suggesting ketone esters can be beneficial for certain health conditions.

MCT Oil Is One Alternative

Another therapeutic option is to use MCT oil, as this type of fat lends itself readily to ketone production. I consume about 6 ounces of caprylic acid a day, as I require many calories due to my daily exercise. I need at least 3,500 to 4,000 calories a day. I get more than 1,000 calories a day from MCT oils, which works out well for me as I obtain the metabolic benefits discussed here.

MCT oil is also far less expensive than ketone esters. That said, 6 ounces is far more than most people would be able to tolerate. To start, begin taking 1 teaspoon and work your way up from there. Be careful to take them with loads of other fats and don't take more than 4 tablespoons at once — otherwise you will likely get nauseous.

Why Cyclical Ketosis Is so Important

While many believe it's best to remain in nutritional ketosis continuously and indefinitely, I strongly disagree with such advice. I believe it can be highly counterproductive to remain on a continuously low-carb diet.

While it's important to remain on a low-carb diet until you are metabolically flexible and insulin sensitive, which can take months or even years for some really heavy people, once you reach that state, you'll want to increase your carbohydrate level (depending on your exercise level) to 100 or 150 grams once or twice a week, especially around the times you're exercising.

Doing so will actually further improve your metabolic flexibility, as you want to have the ability to seamlessly switch between burning fat and glucose. As mentioned, glucose is the universal fuel, so we have to be able to use that. We just don't want to use it all the time. Christofferson agrees, saying:

Improving Metabolic Health Is Key in Post-COVID World

Lastly, optimizing your metabolic health through nutritional ketosis, which is best done through time-restricted eating and a cyclical ketogenic diet, will help you move forward with greater confidence and less fear in this post-COVID world. As noted by Christofferson:

To learn more, be sure to pick up a copy of Christofferson's book "Ketones, The Fourth Fuel: Warburg to Krebs to Veech, the 250 Year Journey to Find the Fountain of Youth." This really is the information you need right now, so the timing of the publication of this book couldn't be more appropriate.

In the interview, Christofferson also reviews some of the history of the key doctors and scientists responsible for identifying and understanding ketone metabolism — including Otto Warburg, Hans Adolf Krebs, George Cahill and Richard Veech — so for more details, be sure to listen to the interview.

Analysis by 

Dr. Joseph Mercola