Ketosis and insulin synthesis: what is normal?

At the heart of the debate about most low carbohydrate diets are fundamental questions about what is a normal diet and how the human body is supposed to operate. These questions can be summarized as follows. Nutritive carbohydrates (primarily starches and sugars, in particular, glucose) are relatively easily digested and are absorbed in the intestines and become blood sugar. Blood glucose is used by cells in the body for the energy needed for their basic functions; about 2/3 of body cells require insulin in order to take glucose into the cell. Excessive amounts of blood glucose are thought to be a primary cause of the complications of diabetes; when glucose reacts with body proteins (resulting in glycosolated proteins) and change their behavior. Perhaps for this reason, the amount of glucose tightly maintained in the blood is quite low. In general, unless a meal is very low in starches and sugars, blood glucose will rise for a period of an hour or two after a meal. When this occurs, beta cells in the pancreas automatically release insulin to cause uptake of glucose into cells. In liver and muscle cells, more glucose is taken in than is needed and stored as glycogen (once called 'animal starch'). Diets with a high starch/sugar content, therefore, cause release of more insulin and so more cell absorption. In non-diabetics, glucose levels vary in time with meals and vary a little more as a result of high carbohydrate content meals. In non-diabetics, blood sugar levels are restored to normal levels within an hour or two, regardless of the content of a meal.

Starvation, or a diet very low in starches and sugars (ie, low-carbohydrate diets), can cause blood sugar levels to fall so low that there is insufficient glucose to fuel the cells in the body. This state causes the pancreas to produce glucagon. Glucagon then stimulates the liver into converting stored glycogen into glucose and then the liver releases it into the blood. Muscle glycogen is never released back into the blood as muscles cells lack the necessary enzymatic machinery to do so. Once liver glycogen stores are exhausted, the liver then begins to burn (metabolize) fatty acids, and releases them into the blood as an alternative fuel source. During fat metabolism, three kinds of ketone bodies are produced as intermediate byproducts. In addition, the liver begins to break down certain proteins into their constituent amino acids to make glucose (gluconeogenesis). Since most cells in the body can use ketone bodies for energy if glucose is unavailable, non-starvation diets low in carbohydrates seldom result in dangerously low levels of blood sugar (hypoglycemia), or dangerously high levels of ketones also know as ketoacidosis. People who eschew low carbohydrate diets cite hypoglycemia and ketoacidosis as a risk factor, but these issues are only problematic for people who already have gluconeogenesis and ketone body regulation impairments.

The diets of most people in modern western nations, perhaps most especially the United States, contain large amounts of starches and frequently significant amounts of sugars, including fructose). As such, the metabolisms of most westerners do not exhaust stored glycogen supplies and so are less likely than people eating other diets to regularly go into ketosis, that is, to convert to using fat for fuel. This has been regarded by medical science in the last century as normal for humans. Ketosis has been thought somewhat dangerous and potentially life-threatening, unnecessarily stressing the liver and causing destruction of muscle tissues. Certainly, ketoacidosis, an extreme ketoic condition, is quite dangerous. A perception has developed that getting energy from protein rather than carbohydrates causes liver damage and that getting energy from fats rather than carbohydrates causes heart disease and other health problems. This view is still held by the majority of those in the medical and nutritional science communities.[59][60][61] However, the common opinion in modern times is that periodic ketosis is in fact normal and sometimes necessary.

Most advocates of low-carbohydrate diets, specifically those that recommend diets similar to the Atkins Diet, argue that maintaining a metabolic state where glucose is the primary energy source in the body is not normal at all and that the human body is in fact supposed to function primarily in ketosis. They argue that high insulin levels can cause many health problems, most significantly fat storage and weight gain. They argue that the purported dangers of ketosis are unsubstantiated (some of the arguments against ketosis result from confusion between ketosis and ketoacidosis which is a related and very dangerous condition). They also argue that fat in the diet only contributes to heart disease in the presence of high insulin levels and that if the diet is instead adjusted to induce ketosis, fat and cholesterol in the diet are not a major concern (although most do not advocate unrestricted fat intake and do advocate avoiding trans fat). Further, it is argued that whereas insulin in the bloodstream causes storage of food energy, excess ketones which contain excess energy are excreted in the urine and the breath when the body is in ketosis.