Our Brain Runs on Energy, Not Willpower

How Astrocytes and Mitochondria Shape Cognitive Health

A fascinating new review published in Reviews in Neuroscience by Coronado-Monroy & Massieu (2025) shines a spotlight on an often-overlooked truth: the brain’s ability to think, remember, and adapt is governed not just by neurons, but by the energy factories that power them and the glial cells that support them.

The review, titled “The versatile and multifacetic role of astrocytes in response to ketogenic interventions,” pulls together emerging evidence that metabolic therapies—like ketogenic diets, fasting, ketone supplements, medium-chain fats, and even exercise—work because they change how astrocytes and mitochondria behave. And these changes ripple across the entire brain network.

Most people still imagine the brain as a wiring diagram of neurons. But modern neuroscience tells a very different story:

The brain is a living energy network, and its performance depends on how well that network manages fuel.

A Bigger Picture: The Brain as a Metabolic Ecosystem

Neurons do the talking, but astrocytes do the managing.

Astrocytes are star-shaped support cells that wrap around blood vessels, clear neurotransmitters, recycle nutrients, protect neurons from stress, and even help shape memory formation. They are the metabolic planners of the brain—deciding which neuron gets fuel, when, and how much.

The new review shows that when ketone levels rise—whether from fasting, diet, MCT oils, or exercise—astrocytes:

• Remodel their shape to better support neurons

• Increase their ability to clear glutamate (reducing excitotoxic stress)

• Strengthen their antioxidant defenses

• Shift their internal metabolism toward greater efficiency

• Produce or consume ketone bodies depending on demand

• Communicate more effectively with neurons through calcium signals

• Support plasticity, learning, and cognitive resilience

In other words: astrocytes thrive under metabolic challenge.

And when astrocytes thrive, neurons can finally do their job with clarity and stability.

Mitochondria: The Real Engines of Thought

If astrocytes are the planners, mitochondria are the engines.

Every mental event—every thought, memory, emotion, sensation—depends on a burst of ATP produced by mitochondria.

What this review highlights, and what decades of research now support, is that ketone bodies enhance mitochondrial function across brain cells:

• Mitochondria burn ketones more efficiently than glucose

• They produce fewer damaging free radicals

• They enter a state of “metabolic calmness” that protects them during stress

• They repair themselves more effectively

• They stabilize the TCA cycle, the biochemical core of energy production

• They communicate danger or sufficiency through metabolites like α-ketoglutarate and succinate

• They regulate the epigenetic signals needed for learning and memory

This means that ketones don’t just “feed the brain”—they tune the entire energy orchestra.

Why This Matters: Metabolic Therapy Is Brain Therapy

From depression and anxiety to brain fog, Alzheimer’s, epilepsy, and long-COVID fatigue, many brain-based symptoms share one underlying theme:

A mismatch between demand and fuel.

When life is stressful, sleep is poor, diet is unstable, inflammation rises, or energy intake is inconsistent, the brain enters a state of bioenergetic strain.

Astrocytes struggle.

Mitochondria become inefficient.

Neurons lose resilience.

Microglia become inflamed.

Cognitive performance drops—not because of “weakness” or “lack of motivation,” but because the brain’s cells simply don’t have enough energy to support optimal function.

This is where metabolic therapies come in.

Ketogenic diets, intermittent fasting, MCT oils, ketone esters, and structured exercise offer alternative fuel routes that bypass metabolic bottlenecks. They give the brain a cleaner, more efficient energy source—and this review demonstrates that astrocytes are key to transforming that fuel into resilience.

A New Way to Think About Brain Health

Instead of viewing the brain as a circuit board, we can now understand it as a bioenergetic ecosystem.Its performance depends on:

• Astrocytes that allocate resources

• Mitochondria that convert fuel into ATP

• Neurons that perform computation

• Microglia that adjust inflammation based on metabolic cues

• TCA cycle metabolites that act like biochemical messages across the network

This gives us a better roadmap for prevention and healing.

When you support your metabolic system, you support your brain.

And this is why ketogenic strategies—whether applied fully, partially, or intermittently—have shown benefits in:

• Cognitive clarity

• Mood stability

• Neuroprotection

• Aging resilience

• Stress tolerance

• Seizure control

• Metabolic disorders

Not because ketones are magic, but because they upgrade the energy network that makes thought itself possible.

The Takeaway

This new review reminds us of something simple yet profound:

A healthy brain isn’t just a neuron-rich brain—it’s an energy-efficient brain.

Astrocytes set the rules. Mitochondria power the action. Metabolic therapies change the game.

By shifting how your brain fuels itself, you can improve how it adapts, learns, and repairs.And in a world full of constant demands, that may be one of the most powerful tools we have for protecting long-term cognitive and emotional health.

Coronado-Monroy, P., & Massieu, L. (2025). The versatile and multifacetic role of astrocytes in response to ketogenic interventions. Reviews in Neuroscience. Advance online publication. https://doi.org/10.1515/revneuro-2025-0096