Raising blood ketone levels with an oral supplement improves metabolic health in a rat model, mimicking effects commonly linked to fasting or ketogenic diets. Digest
Metabolic syndrome, a cluster of conditions including high blood pressure, high blood sugar, and excess body fat, is a major risk factor for heart disease and diabetes, and may be improved by raising blood ketone levels. However, achieving this often requires strict dietary interventions like fasting or ketogenic diets, which many people find difficult to sustain. That's why scientists tested whether raising ketones with a simple oral supplement could reproduce some of these protective effects without requiring major lifestyle changes.
The team studied a strain of rats prone to metabolic health problems. One group received drinking water with 20 percent 1,3-butanediol, a compound converted by the body into the ketone β-hydroxybutyrate. Another group was given plain water. To see how the compound affected the animals, the researchers measured outcomes related to metabolism, fat storage, cardiovascular function, and gene regulation.
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The supplemented rats showed broad improvements compared with controls:
- Blood levels of β-hydroxybutyrate rose, confirming the compound increased ketones.
- Body weight and fasting glucose decreased.
- Average systolic blood pressure over 24 hours dropped in both sexes.
- A specific chemical tag on DNA-packaging proteins increased in kidney, liver, and heart in both sexes, and in skeletal muscle in males.
- Increases in this chemical tag correlated with higher expression of lipid‑metabolism genes in female kidney and male heart.
- Measures of fuel use showed a shift toward greater reliance on fat for energy.
- Inflammation signals in the kidney fell in females, and blood chemistry suggested healthier liver function in males.
These findings suggest that β-hydroxybutyrate does more than just provide fuel. By attaching to histones, it changes how DNA is packaged, making fat metabolism genes more active. This epigenetic mechanism, meaning a change in gene activity without altering DNA itself, appears to help the body burn more fat and improve metabolic health. Importantly, some of the effects differed between organs and between males and females, indicating that the response is not uniform across the body.
Conclusion:
The work suggests a shortcut to some of the benefits often linked to fasting or ketogenic diets. Because the results come from a small animal study, it's uncertain how much they apply to humans, but they provide a compelling starting point for testing ketone-based therapies in metabolic diseases. Learn more about ketone supplements and the ketogenic diet in episode #74 featuring Dr. Dominic D'Agostino.