Unraveling the Translational Relevance of β-Hydroxybutyrate as an Intermediate Metabolite and Signaling Molecule.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic pathways and therapeutic potential without original empirical data or systematic review methodology.
PubMed 40806491 · doi:10.3390/ijms26157362
What was done
This narrative review synthesized existing literature on beta-hydroxybutyrate (BHB), focusing on its signaling mechanisms, including the inhibition of Class I histone deacetylases (HDACs) and activation of G-protein-coupled receptors (specifically HCAR2 and FFAR3). The authors evaluated its translational potential across sarcopenia, metabolic disorders, neurodegenerative conditions, and aging.
What was found
The abstract provides no quantitative data or specific numerical effect sizes. It describes qualitative mechanistic pathways showing that BHB regulates gene expression, lipid metabolism, and inflammatory pathways, leading to enhanced mitochondrial function, decreased oxidative stress, and modulation of adipose tissue lipolysis and immune signaling.
Why it matters
It highlights the conceptual shift from viewing ketone bodies purely as starvation-fuel alternatives to recognizing them as potent signaling metabolites with potential multi-organ therapeutic targets in age-related diseases.
Limits
The paper is a non-systematic narrative review providing no primary human or experimental data. The abstract lacks clinical trial findings, quantitative outcomes, safety profiles, or clear dosing regimens necessary to evaluate therapeutic translation.
Cited by
- supports Beta-hydroxybutyrate induces epigenetic modifications via histone deacetylase inhibition and histone beta-hydroxybutyrylation.