The Metabolic Classroom with Dr. Ben Bikman

The Hidden Power of Ketones: Fueling + Signaling

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Jan 5, 2026

Discover the incredible power of beta-hydroxybutyrate (BHB) beyond just fuel. It plays a key role in reducing inflammation and enhancing gene expression, acting almost like a hormone. Learn how BHB activates receptors that shift immune responses and even inhibits the NLRP3 inflammasome linked to chronic diseases. The discussion delves into its potential in treating neurodegeneration and autoimmune diseases, showcasing BHB's importance in mitochondrial health and overall metabolic resilience.

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INSIGHT

Ketones Are Fuel And Signals

Beta-hydroxybutyrate (BHB) is both a fuel and a signaling molecule that alters gene expression and inflammation.
Ben Bikman says this dual role is rare and links metabolic state to broad cellular responses.

INSIGHT

D Versus L BHB And Physiological Levels

D-BHB is the predominant endogenous form while L-BHB is a smaller fraction and less understood.
Ben Bikman notes physiological ketone levels (1–2 mM) are where many signaling effects occur.

INSIGHT

GPR109A Is A Key Ketone Receptor

BHB activates GPR109A (HCAR2), a niacin receptor expressed on immune cells and retina cells.
Ben Bikman explains GPR109A activation reduces cAMP and protein kinase A activity, mediating anti-inflammatory effects.

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Topic Today:

Ketones, particularly BHB, aren’t just backup fuel—they’re powerful signals that affect inflammation, gene expression, and mitochondrial function. This episode shows how BHB acts like a hormone to enhance metabolic health and cellular resilience.

Summary:

In this episode of the Metabolic Classroom, Dr. Bikman explores the remarkable role of beta-hydroxybutyrate (BHB), the most abundant ketone body, as both a metabolic fuel and a cellular signaling molecule. While traditionally seen as mere backup energy, BHB is now recognized as a potent agent that influences gene expression, reduces inflammation, and protects mitochondrial function.

Ben unpacks the dual nature of BHB, describing how it activates specific receptors like GPR109A and FFAR3, modulates immune responses, and directly inhibits the NLRP3 inflammasome, a key player in chronic inflammation. He also highlights how BHB affects epigenetic regulation through HDAC inhibition, enhancing cellular resilience and antioxidant defenses.

The lecture concludes by tying these pathways together to show how ketones—whether produced endogenously or taken as supplements—convey a coordinated biological signal of adaptation and protection. This shift in understanding elevates ketones from mere “backup fuel” to central players in metabolic health.

NOTE: The information presented is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Dr. Bikman is not a clinician—and, he is not your doctor. Always seek the advice of your own qualified health providers with questions you may have regarding medical conditions.

Ben’s favorite yerba mate and fiber: https://ufeelgreat.com/usa/en/c/1BA884

Exogenous ketones: A high-quality option is the NSF-certified goBHB from Clean Form Nutrition, where you can use the code BEN10 for a 10% discount: https://cleanformnutrition.com/products/go-bhb

Ben’s favorite meal-replacement shake: https://gethlth.com (discount: BEN10)

Ben’s favorite health check-up for men: https://blokes.co/drben15 (discount: DRBEN15)

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