The Metabolic Classroom with Dr. Ben Bikman

Episode Title: Ketones and Your Heart – How Ketones Protect the Cardiovascular System
Release Date: November 24, 2025
Host: Dr. Ben Bikman

Episode Overview

In this science-driven episode, Dr. Ben Bikman breaks down the multifaceted relationship between ketones—specifically beta-hydroxybutyrate (BHB)—and cardiovascular health. He explains how ketones are not merely an alternative fuel source, but metabolic signals that protect the heart. Drawing from the latest research, Dr. Bikman explores how ketones enhance energy efficiency, promote vasodilation, dampen inflammation, encourage antioxidant defenses, and improve heart resilience, especially in the context of heart failure.

Key Discussion Points & Insights

1. The Heart’s Metabolic Demands & Fuel Use

[02:02]

• The heart is “a metabolic powerhouse,” producing about 6 kg of ATP daily, more than its own weight.
• Normal fuel use: 40–70% fatty acids, 20–30% glucose, with some lactate and ketones.
• Ketones are not just a ‘backup’ fuel; they become adaptive, especially under stress.

“Ketones are far more than just a fuel for the heart. They're metabolically active molecules that reduce cardiac workload, relax blood vessels, dampen inflammation, and modulate gene expression in ways that promote cardiovascular resilience.”
—Dr. Ben Bikman [01:54]

2. Ketones’ Bioenergetic Advantages

[04:45]

• Thrifty Fuel Hypothesis: Ketones (BHB) are more oxygen-efficient than fats.
  • ATP per oxygen atom (P/O ratio): BHB ≈ 2.5 vs. Fatty acids ≈ 2.33.
  • BHB generates more ATP per gram than glucose (10,500g vs. 8,500g per 100g substrate).
• Clinical Relevance: When the heart’s ability to use fats/glucose falters (e.g., heart failure), ketones step in to supply ATP efficiently.

“If you can produce more ATP for every unit of oxygen, then you have an advantage. Ketones do that.”
—Dr. Ben Bikman [05:47]

3. The Failing Heart & Ketone Adaptation

[07:05]

• Research highlights:
  • Failing hearts increase expression of the enzyme BDH1 for ketone oxidation (Daniel Kelly’s group).
  • Human and animal studies confirm hearts increase ketone use as their preferred fuels dwindle.
  • Boosting ketone supply improves heart contractility (Gary Lopaschuk’s lab, University of Alberta).

“The heart is essentially reprogramming its fuel preference, shifting toward ketone utilization...”
—Dr. Ben Bikman [07:59]

4. Hemodynamic Effects: Ketones Make the Heart’s Job Easier

[09:16]

• Landmark Study (2019, Circulation): Infusing BHB into patients with heart failure improved cardiac output by 2L/min (~40%) and ejection fraction by 8 points.
• **Improvement is dose-dependent and achieved with physiological BHB.
• Effect is achieved by reducing afterload (the resistance the heart pumps against)—not by making the heart beat harder.

“Ketones make the heart's job easier. They reduce the resistance the heart pumps against, allowing it to generate more output with less strain.”
—Dr. Ben Bikman [11:58]

• Further Study: L-BHB enantiomer (form of BHB) increased cardiac output even more (2.7 L/min) primarily through afterload reduction, not increased effort.

5. Mechanisms: Direct Blood Vessel Effects

[13:41]

• Vasorelaxation: BHB causes arterial dilation (~32% increase in diameter), lowering vascular resistance.
• Mechanisms:
  • Alters potassium ion channels in smooth muscle.
  • Increases nitric oxide production (similar but milder than drugs like Cialis).
• Endothelial Effects: Encourages proliferation of microvessels (important for heart’s own blood supply), helping prevent microvascular loss in heart failure.

“BHB increased arterial diameter by about 32%. The bigger that gets, the lower the vascular resistance is.”
—Dr. Ben Bikman [13:57]

6. Ketones as Signaling Molecules

[16:00]

• HDAC Inhibition: BHB acts as a histone deacetylase inhibitor, promoting expression of genes involved in antioxidant defense (FoxO3a, thioredoxin).
• Protein modification: BHB can directly modify proteins, regulating stress/adaptation pathways, adding a whole new layer of cellular resilience.

“BHB functions as an endogenous histone deacetylase inhibitor... opening up the chromatin structure and thereby enhancing the transcription of specific genes.”
—Dr. Ben Bikman [16:39]

7. Anti-Inflammatory Effects

[18:10]

• BHB specifically inhibits the NLRP3 inflammasome, a key driver in heart failure and atherosclerosis.
• Clinical significance: Reduces inflammation that can cause damaging cardiac remodeling.

“If BHB is up, it keeps things turned down. And this was a specific effect to BHB. Other ketones like acetoacetate or acetone did not have this effect.”
—Dr. Ben Bikman [18:57]

• SGLT2 inhibitors (heart/diabetes drugs) may partially work by increasing ketone production and suppressing this inflammasome.

8. Antioxidant Defense & Oxidative Stress

[20:00]

• BHB ups production of antioxidant genes.
• Ketone oxidation produces fewer reactive oxygen species (ROS) than fatty acids.
• Directly upregulates thioredoxin 1, key for neutralizing oxidative stress.

9. Cardiac Remodeling: Protection & Prevention

[24:25]

• Chronic BHB infusions in animal models prevent or reverse heart failure markers:
  • Stabilizes heart pressure and heart rate.
  • Maintains ejection fraction and cardiac output.
  • Prevents hypertrophic thickening (muscle growing too thick/small chambers).

“BHB prevented all of this in heart failure with compromised ejection fraction... Again, a pretty remarkable finding.”
—Dr. Ben Bikman [25:10]

10. Practical Takeaways & Recommendations

[26:16]

• Ketogenic Diet: Can help reprogram enzymes for better energy production. Effects are nuanced; long-term ketogenic diets may have side effects like increased uric acid, but BHB can counteract inflammation.
• Exogenous Ketones: Especially L-BHB, may be practical for raising ketones without strict diet adherence. “If you’re interested in L-BHB, you’ve really got to focus on exogenous ketones. Your own production... is very modest.” [27:22]
• Summary of Ketone Benefits:
  • Efficient fuel, especially when heart can’t use other fuels.
  • Reduces cardiac workload (afterload), increases output without strain.
  • Dampens harmful inflammation.
  • Increases endogenous antioxidant defenses.
  • Protects microvasculature, supports healthy remodeling.

“Ketones, most especially BHB, serve the heart in multifaceted ways that extend far beyond simple fuel provision. As anti-inflammatory agents, they specifically inhibit the inflammasome, reducing inflammation that can drive adverse cardiac remodeling, not to mention atherosclerosis. As antioxidant promoters, they upregulate myriad antioxidant genes, which just helps... reduce oxidative stress.”
—Dr. Ben Bikman [28:12]

11. Addressing Ketone Skepticism

• Many reject ketones due to nutritional ideology or lack of knowledge.
• The science supports their adaptive, protective value for both failing hearts and brains.

“People’s general wariness of ketones, I would say born primarily from ignorance, causes them to... overlook many of the benefits from these very well conducted studies that I’ve outlined.”
—Dr. Ben Bikman [29:35]

Notable Quotes & Memorable Moments

• “The fact that the failing heart actively upregulates its ketone oxidation machinery tells us something important about the adaptive value of these molecules.”—Dr. Ben Bikman [29:01]
• “Ketones represent what we might call a metabolic signal of fasting, a signal that paradoxically can improve cardiovascular resilience.”—Dr. Ben Bikman [29:07]

Important Timestamps

• [01:54] — Episode theme statement
• [04:45] — Thrifty fuel hypothesis explained
• [09:16] — Landmark clinical study on ketones in heart failure
• [13:41] — How ketones relax blood vessels
• [16:00] — Ketones as gene regulators/signaling molecules
• [18:10] — Ketones and inflammation suppression (NLRP3 inflammasome)
• [24:25] — Cardiac remodeling and ketone protection
• [26:16] — Practical applications: ketogenic diet and exogenous ketones
• [28:12] — Multi-pronged summary of ketone benefits

Final Thoughts

Dr. Bikman demonstrates, with clear scientific rationale and citations, that ketones, especially BHB, are powerful allies for cardiovascular health. Their benefits extend well beyond fuel provision: they reprogram heart metabolism, lower cardiac strain, restrain inflammation, foster antioxidant defenses, and preserve heart structure and microvasculature. For heart failure and cardiovascular risk, properly harnessed ketones may become a cornerstone of metabolic therapy.

Host Sign Off:
“Class dismissed. Until next time. More knowledge, Better Health.”