The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate food plan that mimics fasting metabolism to increase ketone body generation. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy, and it has rapidly gained research attention in the last decade, owing to emerging evidence of the KD's promising therapeutic potential for a variety of diseases other than epilepsy, ranging from obesity to malignancies. In this review, we outline the experimental and/or clinical evidence of the KD's effectiveness and safety in various disorders, and we address putative mechanisms of action based on recent breakthroughs in understanding the KD's effects at the cellular and molecular levels.
We underline that the KD may work through a variety of pathways that need to be investigated further. The difficulties and future opportunities for the therapeutic use of the KD in the treatment of a wide range of disorders have been highlighted. We propose that, given encouraging evidence of therapeutic efficacy and a growing understanding of the mechanisms of action, randomized controlled trials be done to lay the groundwork for clinical usage of the KD.
Introduction
The exact meaning of the Chinese phrase "(bng cóng Ku rù), originally documented in the Tsin/Jin () Dynasty, was once supposed to communicate the notion of dietetic cleanliness; nonetheless, the idiom now accurately underlines the reality that dietary variables are strongly related to numerous illnesses.
1. Dietary planning is becoming increasingly popular, not just as a health-maintenance intervention but also as an essential non-pharmaceutical alternative for illness prevention. A healthy diet may have a significant impact on one's health and may even have therapeutic benefits.
There are numerous types of diets available today, including low-carbohydrate diets (LCDs; e.g., ketogenic diet [KD]), paleo-type diets, plant-forward diets, intermittent fasting, clean eating, traditional regional diets (e.g., Mediterranean diet), and other specifically designed diets that diversify food patterns or fulfill specific purposes (e.g., dietary approaches to stop hypertension diet, Mayo Clinic diet). As experimental and clinical research on microbiota has exploded in the last decade, the importance of microbiota in health and illness has become well-known.
2. Recently, it was shown that microbiota-directed food creation, which was designed to exert therapeutic effects through the modulation of gut microbiota components, is a successful dietary supplementation therapy for malnourished infants.
.3,4 The KD, one of the diets on the growing list, has a long history of therapeutic usage and has lately attracted substantial interest due to its intriguing prospective benefits on a wide range of disorders.
The KD contains a high fat component, extremely low carbs, and enough proteins (Fig. 1),5,6,7 and has been therapeutically utilized to manage seizures in patients with epilepsy since the early 1920s, particularly those who do not react satisfactorily to antiepileptic drugs.
7,8,9 Fasting has been acknowledged as an effective therapeutic against epilepsy and has even been described in the Hippocratic Collection, but dietary therapies employed as "cures" for epilepsy may date back to 500 BC.
8. Fasting was first used as an antiepileptic treatment in 19118, when it was discovered that a diet high in fat but low in carbohydrates could produce acetone and beta-hydroxybutyric acid (-HB), similar to starvation and that alternative ketonemia-producing approaches could produce effects similar to fasting. 5. In 1921, Russel Wilder coined the term "ketogenic diet" after proposing that a ketone-producing diet could be as effective as fasting in the treatment of epilepsy.8 The KD, in particular, can mimic the metabolic consequences of fasting without causing considerable calorie loss. For about a decade before the development of antiepileptic drugs like diphenylhydantoin, the KD was widely used as a medicinal strategy for treating epilepsy. 8
The composition and metabolic effects of the ketogenic diet, which have increasingly generated interest. The compositional features of the classic KD and its variants are shown.
b The number of publications obtained for the search term “ketogenic diet” in PubMed is shown by the year of publication. Articles published before 1931 were not included due to the unavailability of PubMed records predating this timepoint
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