Ketosis is a metabolic process which provides an alternative fuel source for the cells in the body during a low intake of carbohydrates. The hormonal changes associated with a low carbohydrate diet involve the reduction in the circulating levels of insulin, together with an increase glucagon levels. These adaptations form a cornerstone of ketogenic diet which gained a lot of popularity over recent years.

Ketogenic diets are characterized by a reduction in carbohydrates (usually to the amount less than 50 grams per day) and a relative increase in the proportions of protein and fat. The pioneering work of Cahill and colleagues in the 1960s demonstrated exact metabolic effects in classic ketogenic diets, but this approach was already successfully used in the treatment of epilepsy in the early 1920s.

Principles of ketogenic diet

Low-carbohydrate diets are considered to contain less than 100 grams or less than 30% of energy from carbohydrate per day. Such diet usually contains an increased proportion of the other macronutrients (i.e. protein and fat); hence the name “high-protein” or “high-fat” diet. Dietary fat can serve as caloric ballast and add to the taste.

The macronutrient composition of the diet is an important determinant of ketosis. The restriction of carbohydrate represents a more significant element of ketosis than restriction of total calories. Ketosis is thought to occur when fat intake in ketogenic diet exceeds twice the carbohydrate intake plus half the protein intake.

Several mechanisms are proposed by which ketogenic low-carbohydrate diets may influence weight loss. Some of the intial weight loss is a result of diuresis, which encompasses both glycogen depletion and ketonuria – in turn, renal sodium and water loss are increased. Although it has been often stated that ketogenic diets suppress hunger, more research is needed on that issue.

Ketone bodies also suppress appetite and create a metabolic advantage by increasing gluconeogenesis and up-regulating mitochondrial biogenesis. The latter denotes the formation of new mitochondria and subsequent production of extra energy. Other mechanisms include limitation of food choices, the satiating effect of high-protein intake, increased adipose tissue lipolysis, increased fatty acid oxidation and reduced palatability of low-carbohydrate diets.

As with any other fat-loss diet, exercise improves the success of the ketogenic diet. Still, high-intensity physical activity is unsustainable in a diet devoid of carbohydrates; therefore carbohydrates must be incorporated into the dietary regimen without disrupting the effects of ketosis. Modified approaches for such cases are known as the targeted ketogenic diet and the cyclical ketogenic diet.

Therapeutic roles

A long-term ketogenic diet can significantly reduce the body weight and body mass index without any significant side effects. In addition, it can also reverse the risk of heart disease, primarily due to the improvement of lipid profiles. It lowers blood pressure, LDL cholesterol (colloquially known as the “bad” cholesterol) and increases HDL cholesterol (also known as the “good” cholesterol).

Since 1920, the ketogenic diet has been used as an effective approach in the treatment of severe childhood epilepsy, but the interest waned following the introduction of anticonvulsant drugs. Today it can be considered as an option for children with intractable epilepsy who use multiple antiepileptic drugs. It is also a treatment of choice for seizures associated with glucose transporter type 1 deficiency syndrome (i.e. De Vivo disease).

Individuals with insulin resistance, type 2 diabetes and metabolic syndrome are likely to see symptomatic and objective improvements in biomarkers of disease risk after introducing well-formulated ketogenic diet. Glucose control improves not only as a result of less glucose coming in, but also due to the increased sensitivity of cells to insulin.

The metabolic effects of a ketogenic diet lead to a higher-than-usual oxidation of fats, which suggest reduced respiratory exchange ratio values. This can lead to potential useful effects of this diet in patients with increased carbon dioxide as a consequence of respiratory failure. More research is needed to evaluate the effectiveness and safety of ketogenic diet in other conditions.