Ketogenic diet: what it is and what it is used for

By Cristiano Antonino On Jan 20, 2023

The ketogenic diet (KD) is a diet high in fatty acids and low in carbohydrates, with an adequate protein content

This type of diet, which results in a drastic reduction in carbohydrate intake, causes a change in metabolism by mimicking fasting, making immediate changes in lipid and fatty acid metabolism.

The ketone bodies produced, especially β-hydroxybutyrate, acetoacetate and acetone become the body’s main substrates for energy production.

This process, known as ketosis, is generally accompanied by metabolic acidosis

In addition, the change in the main energy substrate causes a simultaneous change in the microbiota, increasing the Bacteroidetes:Firmicutes ratio.

It is possible that the introduction of such a new diet may initially lead to the onset of different side effects such as nausea, constipation, asthenia and rarely difficulty breathing.

There are different versions of the ketogenic diet based on the ratio of fats, proteins and carbohydrates

The macronutrient that differentiates the different variants of ketogenic diets is the amount of lipids, as opposed to carbohydrates:

The classic ketogenic diet (cKD), the first ketogenic diet to be created, is the one with the tightest fat to carbohydrate ratio (4:1);
The traditional medium chain triglyceride ketogenic diet (tMCTKD) within which medium chain fatty acids (MCT) are introduced;
The modified medium chain triglyceride ketogenic diet (mMCTKD);
The modified Atkins ketogenic diet (MAD).

When creating a customised ketogenic diet it is necessary to know the level of ketosis you want to achieve.

This level is called the ‘ketogenic ratio’ and represents the ratio of grams of lipids to the sum of grams of protein and carbohydrates.

The higher the ketogenic ratio, ranging from 4:1 to 1:1, the higher the level of circulating ketone bodies.

Over time, the uses of the ketogenic diet have expanded to include not only epileptic diseases in children, but also treatment schemes for obesity and diabetes or, in recent times, adjuvant treatments for obesity and cancer diseases.

With regard to the treatment of epilepsies, the ketogenic diet is reserved for drug-resistant forms

In patients suffering from epilepsy, the ketogenic diet induces changes in serum levels of fatty acids, ketone bodies, glucose and insulin by increasing circulating levels of GABA (amino-butyric acid), mitochondrial activation, oxidative phosphorylation and simultaneously reducing neuronal excitability and activation, with the final effect of bringing about neuronal stabilisation and thus a reduction in the excitability of epileptogenic areas.

The ketogenic diet was introduced for the treatment of drug-resistant epilepsies in paediatrics around 1920, but only in the last twenty years has the use of such diets become an integral and central part of therapy.

There is much data on nutritional status, growth and bone health in these patients, where frequent monitoring is necessary to maintain diet optimisation.

If the efficacy on seizure frequency is indisputable (reduction of about 70% of episodes since the introduction of the diet), the metabolic effects on growth and bone metabolism are more controversial.

There appears to be literature data showing a reduction in bone mineral density and a parallel increase in the risk of fractures, but these results do not seem unequivocally confirmed.

Likewise, discrepant data are present regarding the linear growth in height and weight of these patients, but the present data are based on short follow-ups with a maximum of two years.

Finally, with regard to micronutrient deficits, and in particular selenium deficiency, which is responsible for cardiomyopathy and ST-tract elongation, it is necessary to monitor plasma levels, as specific supplementation is possible.

Supplements containing carnitine have also been suggested among the micronutrients to be supplemented.

In addition, specific attention should be paid to the lipid profile of these patients, as hypercholesterolaemia (in particular an increase in LDL-cholesterol), hypertriglyceridaemia and an increase in apolipoprotein B levels have been observed.

Ketogenic diet in paediatrics

Further indications for treatment with a ketogenic diet in paediatrics are currently limited, although steadily increasing.

A recent application with good clinical results is as a therapy for certain metabolic diseases such as glucose transporter type 1 deficiency (GLUT1 deficiency), certain glycogenoses or pyruvate dehydrogenase defect (PHD).

In these three diseases, the ketogenic diet is a real cure for the underlying disease, while in other metabolic diseases it can alleviate the progression of some of the symptoms of the disease itself, particularly seizures.

Regarding the treatment of paediatric obesity, few data are yet available. Recent data, published in 2021, showed encouraging results regarding the use of such treatment.

Childhood obesity is mainly linked to an excessive consumption of carbohydrates and therefore, the introduction of a dietary regimen with a fixed and established ratio of fat and a very low carbohydrate intake could lead to visible effects in a relatively short time.

Metabolic effects, in addition to weight reduction, are a reduction in triglyceride levels, cholesterol and blood pressure, with a parallel increase in ‘good’ cholesterol (high-density lipoprotein, HDL).

Finally, the presence of circulating ketones and its metabolic effects described above regulate and inhibit the sense of satiety.

The latest application of the ketogenic diet is its use as an adjuvant therapy in cancer diseases

The ketogenic diet should starve neoplastic cells, reducing their ability to utilise glucose, while normal cells would be able to adapt and use ketone bodies as an energy substrate.

Another benefit of the ketogenic diet could be related to the reduction in circulating insulin, which secondarily leads to a reduction in the insulin-like factor responsible for the proliferation of neoplastic cells.

In the light of this evidence, the role assumed by the ketogenic diet is that of a true pharmaconutrition, representing a central role in the patient’s therapeutic approach and, therefore, it must be customised and modified throughout the therapeutic course according to the child’s needs and growth requirements.

In fact, regular weight and body growth, even in these subjects on a ketogenic diet, represents the target to be reached as an index of good control of the basic disease.

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Like all nutrition, the ketogenic diet can be composed of natural foods or pre-constituted formulas and can be administered orally or by means of artificial nutrition supports (nasogastric tube, gastrostomy, jejunostomy).

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