124: How Ketones Help the Brain Recover From Concussions with Dr. Ben Bikman

Bikman builds the case that the metabolic crisis begins within minutes of impact, so waiting until after injury to provide ketones may miss the earliest window of vulnerability. He argues that 'metabolic preparedness'—having ketones already on board—is a logical preventative measure. He acknowledges that a ketogenic diet could achieve this, but many athletes resist such restrictions, making exogenous ketones the practical choice. He emphasizes that the brain is opportunistic and will use whichever fuel is present; if ketones are available, the brain will prioritize them, deriving over two-thirds of its ATP from ketones when both fuels are present. This protocol is about ensuring that at the moment of injury, the brain isn't solely reliant on a fuel it suddenly can't use.

Bikman explains that in the acute phase after injury, there is a marked increase in energy demand, but glucose transport and glycolysis are compromised, leaving neurons vulnerable. Animal models show that ketones can reduce lesion volume by approximately 50% compared to glucose-fed controls. Human microdialysis data confirm that blood ketones readily reach the injured brain. He stresses that the metabolic dysfunction can persist for days even in mild cases, so sustained ketone availability is important. This protocol is about immediate intervention to limit the primary energy failure and the downstream oxidative and inflammatory cascades. He also notes that ketones promote BDNF and neuroplasticity, aiding longer-term repair.

Bikman references George Cahill's classic fasting studies, which demonstrated that the human brain will derive the majority of its energy from ketones when both glucose and ketones are available, exceeding a 2:1 ratio. He laments that for most modern individuals, frequent eating and high-carbohydrate diets keep insulin elevated, suppressing ketone production and leaving the brain metabolically reliant on glucose. This creates a state of vulnerability where any disruption to glucose metabolism—like a concussion—leaves the brain without a backup. By adopting a low-carb or fasting lifestyle, one builds metabolic flexibility into the brain, so it is never caught without an alternative fuel. He notes that this is a form of 'metabolic preparedness' that doesn't require exogenous supplements, though exogenous ketones can complement or substitute for diet.

Bikman highlights a practical barrier: even if the science supports ketone use, universities and professional organizations cannot openly recommend or supply supplements that haven't passed rigorous third-party testing. He announces that the first NSF-certified ketone supplement is now available (Cleanform Nutrition), solving this problem. He notes that this certification is crucial for widespread adoption in athletics, as it removes the liability and regulatory hurdles. He provides a direct link and discount code for this product, indicating a personal relationship with the company.

Bikman warns that the supplement market includes products labeled as 'ketone' that are not based on BHB. He explains that these alternatives must be converted to BHB in the liver, and in the process may create harm. He specifically recommends looking for 'goBHB' on the label, a patented form that ensures the product contains actual BHB. This is a practical shopping tip to avoid ineffective or potentially harmful products. He ties this back to the concussion context: when the brain urgently needs fuel, you want the most direct, bioavailable form, not something that requires metabolic processing.

Bikman explains that the brain, despite being only 2% of body mass, consumes 20% of total energy. After a concussion, glucose transporter expression (GLUT1 at the blood-brain barrier, GLUT3 on neurons) drops within hours, limiting glucose entry even when blood glucose is abundant. Inside cells, key glycolytic enzymes like hexokinase, phosphofructokinase, and pyruvate dehydrogenase are inhibited due to calcium influx and oxidative stress. This creates a bottleneck that sharply reduces ATP production. The energy demand actually spikes acutely after injury, but the glucose-dependent brain cannot meet it, leaving neurons vulnerable to 'going hungry.' This metabolic dysfunction can persist for days even in mild cases, contributing to symptoms like brain fog, fatigue, and slow thinking. The concept of an 'energy crisis' provides a unifying explanation for why the brain struggles and why alternative fuels could be therapeutic.

Bikman details that ketones (BHB and acetoacetate) are produced in the liver during fasting or carbohydrate restriction. They cross the blood-brain barrier via MCTs, which are distinct from glucose transporters. Critically, after a traumatic brain injury, the expression of these MCTs increases within hours, enhancing the brain's capacity to take up ketones. Once inside neurons, BHB is converted to acetyl-CoA and enters the citrate cycle directly, bypassing glycolysis entirely. This means the compromised glucose transport and inhibited glycolytic enzymes become irrelevant. He cites classic fasting studies by George Cahill showing that when both glucose and ketones are available, the human brain derives over two-thirds of its ATP from ketones, demonstrating that the brain is 'opportunistic' and will use whichever fuel is most available and metabolizable. In animal models of TBI, ketogenic diets or infused BHB increased brain ketone uptake by up to 50%, restored ATP, and reduced lesion volume by approximately 50% compared to glucose-fed controls. A human microdialysis study (Bernini et al., 2018) confirmed that blood ketones readily track into the injured brain, rising with fasting and falling with carbohydrate feeding, validating the translational potential.

Bikman argues that because the metabolic crisis begins immediately upon impact, having ketones already circulating could provide instant metabolic support, preventing the ATP depletion that drives neuronal damage. He acknowledges that a ketogenic diet can achieve this, but many athletes are unwilling to adopt such strict dietary restrictions, and metabolically they may not need it for performance. Therefore, exogenous ketones become the obvious practical solution. He suggests that providing BHB before and during activity ensures the brain has access to an alternative energy source even if injury occurs. This concept of 'metabolic preparedness' extends beyond athletes to anyone at higher risk of head injury, such as military personnel or construction workers. He also notes that post-injury, exogenous ketones can bridge the metabolic gap while glucose metabolism remains impaired for days.

Bikman explains that after a concussion, reactive oxygen species (ROS) generation increases rapidly due to mitochondrial electron leak, causing oxidative damage to lipids and proteins. Ketones counteract this via BHB's inhibition of class I histone deacetylases, which promotes the expression of endogenous antioxidant genes. In rodent TBI models, a ketogenic diet attenuated oxidative stress by upregulating these defenses. On the inflammation side, concussion triggers a surge in pro-inflammatory cytokines like TNF-alpha, and microglia can amplify the response, extending neuronal injury. BHB inhibits the NLRP3 inflammasome, a master switch that controls the production of multiple pro-inflammatory molecules, thereby promoting a shift toward an anti-inflammatory state. This dual action—energy provision plus signaling—makes ketones uniquely suited to address the multifaceted damage of a concussion.

Bikman notes that BHB has been shown to enhance BDNF, a key growth factor that supports neuron survival, neurogenesis, and synaptic plasticity. This means ketones may actively facilitate the brain's own repair processes after injury, not just keep cells alive. He cites adolescent animal models where prior ketogenic adaptation improved motor recovery and even preserved telomere length, a marker of cellular health and longevity. This suggests that metabolic interventions could influence not only immediate outcomes but also long-term brain resilience, potentially reducing the risk of lingering effects seen in post-concussion syndrome, which affects up to 30% of individuals.