There is a lot of confusion about the term ketosis among medical professionals as well as laypeople. It is important to understand when and why nutritional ketosis occurs, and why it should not be confused with the metabolic disorder we call ketoacidosis.
Ketosis is a metabolic state where the liver produces small organic molecules called ketone bodies.
Most cells in the body can use ketone bodies as a source of energy. When there is a limited supply of external energy sources, such as during prolonged fasting or carbohydrate restriction, ketone bodies can provide energy for most organs.
In this situation, ketosis can be regarded as a reasonable, adaptive physiologic response that is essential for life, enabling us to survive periods of famine.
Nutritional ketosis should not be confused with ketoacidosis, a metabolic condition where the blood becomes acidic as a result of the accumulation of ketone bodies.
Ketoacidosis can have serious consequences and may need urgent medical treatment. The most common forms are diabetic ketoacidosis and alcoholic ketoacidosis.
What Is Ketosis?
The human body can be regarded as a biologic machine. Machines need energy to operate. Some use gasoline, others use electricity, and some use other power resources.
Glucose is the primary fuel for most cells and organs in the body. To obtain energy, cells must take up glucose from the blood. Once glucose enters the cells, a series of metabolic reactions break it down into carbon dioxide and water, releasing energy in the process.
The body has an ability to store excess glucose in the form of glycogen. In this way, energy can be stored for later use. Glycogen consists of long chains of glucose molecules and is primarily found in the liver and skeletal muscle. Liver glycogen stores are used to maintain normal levels of glucose in the blood while muscle glycogen stores are mainly used to fuel muscle activity.
Carbohydrates are the body’s primary source of glucose and other sugar molecules such as fructose and galactose. During carbohydrate restriction, both proteins and fats can be used for energy. In fact, most cells can use fatty acids for energy, but brain cells and developing red cells are more dependent on glucose for energy supply. However, brain cells can adapt and use ketones from fat breakdown for its energy needs.
When no carbohydrate is available, the liver will not break down fat completely. Instead, it produces ketone bodies that are used by most cells to provide energy. When ketone bodies are produced more quickly than the body needs, ketone levels build up in the blood, resulting in a condition known as ketosis. Ketosis is most commonly caused by very low carbohydrate consumption or prolonged fasting.
When the body’s glycogen stores become depleted, the breakdown of body fat (mainly triglycerides) results in increased availability of fatty acids. Most cells can use fatty acids for energy production. However, many fatty acids can not pass the blood-brain barrier. Therefore, the brain becomes dependent on ketone bodies produced by the liver.
The breakdown of fatty acids results in the production of an important substance called acetyl CoA. When fat and carbohydrate metabolism is in the balance, most acetyl CoA enters the so-called citric acid cycle (Krebs cycle) where it is used for energy production. When acetyl CoA cannot enter the citric acid cycle, it is shunted to form ketone bodies. This process is called ketogenesis.
Ketone bodies include three compounds: acetone, acetoacetate, and beta-hydroxybutyrate. Acetone can sometimes be smelled from the breaths of people with high levels of ketone bodies in the blood. You may be acquainted with the smell because some nail polish removers contain acetone.
Ketone bodies are not only produced when the glycogen stores become depleted. In fact, ketone bodies are produced by the liver all the time. Research indicates that the heart and kidneys prefer to use ketone bodies rather than glucose as a fuel resource. To dispose of excess ketone bodies, the body uses the kidneys to excrete them in urine, and they are exhaled from the lungs. During ketosis, ketones can easily be detected in the urine.
When daily carbohydrate consumption is restricted to below 60 grams per day, the body usually shifts into ketosis and blood levels of ketone bodies start to rise. At this level of consumption, blood levels of ketone bodies may rise above 0.5 mmol/L, which is ten times higher than among individuals who consume 300 grams of carbohydrate per day. With lower consumption blood levels of ketone bodies rise further, and may reach 3 mmol/L.
The hepatic generation of ketone bodies is the normal physiologic response to fasting. Mild ketosis (ketone body concentration of about 1 mmol/L) develops after a 12- to 14-hour fast. If fasting continues, ketone body concentration continues to rise and peaks at a concentration of 8 to 10 mmol/L. Beta-hydroxybutyrate is the major ketone body that accumulates.
This normal physiological response to varying degree of carbohydrate restriction or fasting is termed nutritional ketosis.
This process is dependent on the ability of the pancreas to produce insulin. If insulin production is limited, the acid-base balance of the body may become interrupted.
It is important to differentiate between ketoacidosis and ketosis.
When ketoacidosis is present, the blood becomes acidic (pH level drops). Increased blood acidity can have serious consequences, cause coma and eventually death if untreated. However, although ketone bodies are acidic, the body usually manages to keep the acidity of the blood within normal limits during carbohydrate restriction or prolonged fasting.
Unlike ketoacidosis, nutritional ketosis is by definition a benign metabolic state, enabling our body to react to a shortage of dietary fuels.
The most common causes of ketoacidosis are diabetic ketoacidosis and alcoholic ketoacidosis. The former is primarily associated with type 1 diabetes, due to a shortage of insulin. The latter occurs primarily among alcoholics.
Although nutritional ketosis is considered safe, it is important to realize that people who are unable to secrete basal insulin, such as type 1 diabetics and some type 2 diabetics, are at more risk of entering unsafe levels of ketosis that may require emergency medical treatment.
Ketogenic diets emphasize foods rich in natural fats and adequate in protein and restrict foods high in carbohydrate. While the standard American diet contains 45-65% of calories from carbohydrate, ketogenic diets usually restrict carbohydrate intake to about 2-4% of calories.
A typical ketogenic meal includes a small amount of protein, a source of natural fats (for example, butter, beef tallow, lard, duck fat, cream, olive oil, or coconut oil) and some green leafy vegetables.
For many of us, a ketogenic diet defies everything we’ve learned about diet and nutrition through the years. That’s why it may be a bit hard for many to accept. Coffee with butter, bacon, steak, cream and fat cheese. Very little fruit. Many will say that such a diet defies common sense. But the fact is that ketogenic diets have been tried and tested, and there is no clear evidence of harm.
Ketogenic diets have been used to treat epilepsy in children. There is some evidence that adults with epilepsy may benefit from such a diet as well. In the 1920’s ketogenic diets were popular due to their efficacy in childhood epilepsy. However, anti-epileptic drugs have largely replaced ketogenic diets as a treatment for epilepsy.
Ketogenic diets usually induce weight loss. Insulin sensitivity is improved, and there may be some other metabolic advances as well. Therefore, low-carbohydrate diets and periodic fasting have become very popular worldwide. Studies indicate that low-carbohydrate diets induce more weight loss, lower triglycerides and raise HDL-cholesterol (the good cholesterol), compared with low-fat diets.
There is some evidence that ketogenic diets may affect the growth of cancer cells and improve the quality of life in cancer patients. However, it is premature to make any recommendations based on current research.
Although nutritional ketosis is an adaptive response triggered by lack of external energy resources, it may initially be associated with unpleasant physical symptoms.
Fasting and carbohydrate restriction leading to ketosis can cause headache, nausea, fatigue, dry mouth, bad breath, upset stomach, nausea, frequent urination, and lack of mental clarity.
The symptoms associated with ketosis are most often temporary and will usually pass in a couple of days. Therefore, they are sometimes called “ketosis flu.” Some of these symptoms are caused by dehydration, and therefore intake of salt and water may be helpful.