The Keto HDAC Myth — How One Paper Misled Millions for a Decade

Story at-a-glance

• A 2013 Science paper claimed beta-hydroxybutyrate (BHB), the primary ketone body produced during ketosis, was a potent histone deacetylase (HDAC) inhibitor with powerful epigenetic benefits — this claim became the foundation of the keto movement's health narrative
• A devastating 2019 head-to-head comparison in Scientific Reports found that BHB shows no detectable HDAC inhibition in vitro or in vivo, while butyrate (a different molecule produced by gut bacteria) demonstrates robust HDAC-inhibiting activity
• The bitter irony: ketogenic diets actually reduce colonic butyrate production by depleting fiber intake and diminishing butyrate-producing gut bacteria — the very diet designed to boost the "HDAC-inhibiting ketone" may be depleting the actual HDAC inhibitor
• While BHB has legitimate benefits as an alternative fuel source and GPR109A receptor activator, the widespread claim that ketosis provides "epigenetic therapy" through HDAC inhibition appears to be scientifically unfounded
• Oral butyrate supplements are largely ineffective because butyrate is absorbed in the small intestine before reaching the colon where it's needed — currently, no commercially available product effectively delivers butyrate to the colon

For the past decade, the ketogenic diet community has promoted a compelling narrative: that entering ketosis produces beta-hydroxybutyrate (BHB), which acts as a powerful histone deacetylase (HDAC) inhibitor, unlocking profound epigenetic benefits that explain many of the diet's purported health advantages.

Analysis by Dr. Joseph Mercola