Table 1.

Epigenetic changes determined by KD.

Epigenetic Modifications	Effect of Ketosis	Possible Mechanisms	Subject of Investigation	Refs
DNA methylation	Global DNA hypomethylation	Increased brain adenosine	Rats	[47]
			Human	[52,54,55]
		Modulation of genes regulating DNA methylation	Rats	[50]
			Human	[57]
		Downregulation of DNMT1, DNMT3a, and DNMT3b	Human (subjects with obesity)	[62]
Histone modifications	Covalent modifications to key histones	Lysine acetylation, methylation, and β-hydroxybutyrylation	Cell lines	[79]
			HEK293 cell, mice	[4,40,80]
		βOHB inhibits class I histone deacetylases	Cell lines	[40]
		βOHB increases histone acetylation	HEK293 cell line	[2,82]
		Sirtuins-mediated histone deacetylation	Cell lines	[40]
		Global increase in protein acetylation	Mice	[60]
		Increased the levels of histone acetylation	Rats	[87]
miRNAs	Elevation of miR-16-5p, miR-196b-5p, and miR-218-5p	Unknown. Changes in these miRNAs are determined by caloric restriction.	Mice	[96]
	Modifications in hsa-let-7b-5p, hsa-miR-143-3p, and hsa-miR-504-5p	Unknown. The target genes of the miRNAs are associated with obesity and metabolism-related pathways.	Human	[97]