Vanderbilt researchers are rethinking delirium, the acute condition that affects up to 80% of ICU patients. A new review out of the Vanderbilt University Medical Center points to an emerging idea in critical care and cognitive health: delirium is a brain energy crisis.
And ketones offer one of the most rapid ways to close that energy gap.
This article breaks down how ketones work in the brain, what the evidence shows, and how these insights may matter both inside and outside the ICU.
And ketones offer one of the most rapid ways to close that energy gap.
This article breaks down how ketones work in the brain, what the evidence shows, and how these insights may matter both inside and outside the ICU.
Understanding ICU Delirium: A Brain Metabolism Problem
Delirium is more than disorientation. It’s a deterioration in cognitive function driven by a combination of systemic inflammation, neurotransmitter imbalance, and impaired brain energy metabolism. It’s tied to longer hospital stays, higher complication rates, sharply increased mortality, and massive health care costs. In fact, an estimated $164 billion in annual healthcare costs is due to delirium’s lasting impact on recovery and cognitive health.
During severe illness, trauma, or infection, inflammatory cytokines flood the bloodstream. The blood–brain barrier becomes leaky. Microglia (the brain’s immune cells) switch into glycolysis, a glucose-hungry energy system.
The result? Microglia start competing with neurons for the same limited glucose supply, creating what the review calls a brain energy gap. This metabolic mismatch is increasingly recognized as a core driver of ICU delirium.
How Ketones Change the Equation
Ketones, especially β-hydroxybutyrate (BHB), bypass the glucose bottleneck entirely, regardless of age or health status.
They cross the blood–brain barrier via monocarboxylate transporters (MCTs) and enter mitochondria directly, producing ATP at a lower oxygen cost than glucose.
That means more usable brain energy under hypoxic or inflamed conditions. But ketones do more than just fuel neurons; they act as a cellular signal that reprograms the whole system by:
- Activating mitochondrial biogenesis (via PGC-1α and sirtuins)
- Boosting antioxidant defenses (glutathione, superoxide dismutase)
- Inhibiting neuroinflammation by blocking the NLRP3 inflammasome, reducing IL-1β and IL-18
- Restoring balance in neurotransmitters by increasing GABA and moderating glutamate excitotoxicity
Together, these effects may stabilize the brain’s internal environment, even as the rest of the body fights to recover.
What the Evidence Shows So Far
From Bench to Bedside
Across models of critical illness, neurodegeneration, and injury, the story is remarkably consistent: when glucose metabolism falters, ketones keep the brain online.
In sepsis-associated encephalopathy, a close analog of ICU delirium, ketone supplementation reduces neuroinflammation, restores mitochondrial efficiency, and limits the metabolic tug-of-war between microglia and neurons.
In traumatic brain injury, ketone esters have been shown to shrink lesion size, dampen inflammation, and accelerate functional recovery.
And in neurodegenerative diseases like Alzheimer’s, clinical trials using ketogenic drinks or medium-chain triglyceride (MCT) formulations have improved cognitive performance within weeks—enhancing memory, focus, and executive function.
In sepsis-associated encephalopathy, a close analog of ICU delirium, ketone supplementation reduces neuroinflammation, restores mitochondrial efficiency, and limits the metabolic tug-of-war between microglia and neurons.
In traumatic brain injury, ketone esters have been shown to shrink lesion size, dampen inflammation, and accelerate functional recovery.
And in neurodegenerative diseases like Alzheimer’s, clinical trials using ketogenic drinks or medium-chain triglyceride (MCT) formulations have improved cognitive performance within weeks—enhancing memory, focus, and executive function.
Human Studies Outside the ICU
Early-stage clinical research mirrors these effects. In adults with mild cognitive impairment or Alzheimer’s disease, daily ketogenic interventions have consistently led to better memory recall, faster processing, clearer language function, and improved day-to-day cognition.
Importantly, multiple safety trials have confirmed that ketone monoesters can raise blood β-hydroxybutyrate (BHB) to 1.5–4.0 mM—levels also found with 1-2 servings of Kenetik’s bioidentical ketone blends—without causing acidosis, instability, or metabolic stress in healthy or at-risk populations.
Evidence in the critically ill is still emerging, but the groundwork is strong. That’s why Kenetik is partnering with Vanderbilt researchers next year to help expand this body of data—bridging lab findings and real-world recovery.
The Brain Energy Gap Beyond the ICU
The metabolic mechanisms described in delirium also occur in other brain states where energy use is impaired. In aging, mild cognitive impairment, and early Alzheimer’s disease, brain glucose uptake can fall by ~20–25%, forcing neurons to rely more heavily on alternative fuel sources like ketones.
Although the Vanderbilt review doesn’t discuss heat stress or mental-load performance states, the core principle is the same: when glucose becomes limited, ketones provide an alternate fuel source.
- Cognitive aging and mild cognitive impairment (where glucose uptake drops up to 25%).
- High-stress performance states like prolonged mental load, heat stress, or hypoxia can all create localized energy deficits.
In every case, ketones offer an alternate route to keep neurons healthy, protecting cognition when energy demand spikes and glucose supply dips.
Practical Takeaways: Using Ketones to Support Mental Performance
While the review focuses on ICU patients, the same metabolic logic helps explain why ketones may support cognitive performance in healthy individuals facing demanding conditions.
For those outside the ICU but inside high-performance domains—athletes, operators, knowledge workers—the parallels are clear: protecting focus under duress means fueling the brain as deliberately as the body.
- Target moderate ketosis. Studies achieving cognitive benefits hit ~1–2 mM BHB, equivalent to one serving of Kenetik’s bioidentical ketone blend of D-BHB Acid and R-1,3BDO.
- Monitor clarity, not intensity. The marker of successful ketone use isn’t a jolt of energy; it’s steadiness: clearer thinking, reduced fog, and more composure under pressure.
- Respect biology. Ketones stabilize systems because they’re a nutrient, not a stimulant. Stack them with hydration, not caffeine for the best effects.
Performance Starts in the Brain
The Vanderbilt review suggests that delirium may be an extreme version of a broader issue: the brain struggling to produce enough energy when it matters most.
Exogenous ketones offer a metabolic bridge. A way to keep the brain running when its primary fuel system fails. In the ICU, that might mean protecting neurons from injury. In everyday life, it could mean preserving clarity, resilience, and cognitive function during the most demanding periods.
Either way, the lesson is the same: Don’t just fuel harder. Fuel smarter. Ketones help the brain stay balanced, focused, and resilient, whether you’re in an ICU, deep in competition, or navigating high-stakes work.
