The value of targeting ketone body metabolism in inflammatory and autoimmune diseases.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms and early clinical data without systematic review methodology.
PubMed 41782033 · doi:10.1186/s12967-026-07884-x
What was done
The authors synthesized literature on the molecular, cellular, and immunometabolic mechanisms of ketone body metabolism, specifically focusing on how beta-hydroxybutyrate modulates immune cells such as macrophages and T cells. They reviewed therapeutic strategies to modulate ketone levels—including the ketogenic diet, exogenous ketone supplements, SGLT2 inhibitors, and metabolic enzyme regulators—and their reported effects in diseases such as multiple sclerosis, inflammatory bowel disease, gout, metabolic dysfunction–associated steatohepatitis, and atherosclerosis.
What was found
No quantitative data or effect sizes were reported in the abstract. The authors report that beta-hydroxybutyrate regulates immune responses by inhibiting the NLRP3 inflammasome, activating the HCAR2 receptor, and inducing epigenetic reprogramming via histone beta-hydroxybutyrylation, resulting in immunomodulatory and anti-inflammatory effects in preclinical models and early clinical evidence.
Why it matters
This review highlights ketone bodies as active signaling metabolites rather than mere energy substrates, outlining an immunometabolic framework for dietary and pharmacological interventions in chronic inflammatory diseases.
Limits
This is a narrative review with no systematic search criteria, quality appraisal, or quantitative pooling. The findings derive largely from preclinical models, and human data are limited to early clinical evidence without reported sample sizes, effect magnitudes, or long-term safety data in the abstract.
Cited by
- supports Beta-hydroxybutyrate acts as a signaling molecule through cell-surface G-protein coupled receptors to produce anti-inflammatory and antioxidant effects.