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Review
. 2022 Aug 8;14(15):3245.
doi: 10.3390/nu14153245.

Epigenome Modulation Induced by Ketogenic Diets

Paola Ungaro  1   2 , Immacolata Cristina Nettore  3 , Fabiana Franchini  3 , Giuseppe Palatucci  3 , Giovanna Muscogiuri  2   3 , Annamaria Colao  2   3 , Paolo Emidio Macchia  2   3
Affiliations
Review

Epigenome Modulation Induced by Ketogenic Diets

Paola Ungaro et al. Nutrients. .

Abstract

Ketogenic diets (KD) are dietary strategies low in carbohydrates, normal in protein, and high, normal, or reduced in fat with or without (Very Low-Calories Ketogenic Diet, VLCKD) a reduced caloric intake. KDs have been shown to be useful in the treatment of obesity, metabolic diseases and related disorders, neurological diseases, and various pathological conditions such as cancer, nonalcoholic liver disease, and chronic pain. Several studies have investigated the intracellular metabolic pathways that contribute to the beneficial effects of these diets. Although epigenetic changes are among the most important determinants of an organism's ability to adapt to environmental changes, data on the epigenetic changes associated with these dietary pathways are still limited. This review provides an overview of the major epigenetic changes associated with KDs.

Keywords: DNA methylation; Very Low-Calories Ketogenic Diet; histone modifications; ketogenic diet; miRNAs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Epigenetic changes induced by KD. KD leads to an increase in circulating ketone bodies (β-hydroxybutyrate [β-HB]). In the brain, higher concentrations of β-HB have inhibitory effects on DNA methyltransferases (DNMT) via an increase in adenosine, which in turn leads to global DNA hypomethylation. Ketone bodies also act as epigenetic modifiers that determine covalent modifications at key histones such as lysine acetylation (Ac), methylation, and β-hydroxybutyrylation (Kbhb). Finally, β-HB is less efficient than glucose as a substrate for NADH production. The increase in the NAD + level promotes histone demethylation via the modulation of sirtuin activity.
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