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The Role of Beta-Hydroxybutyrate (BHB) in Neurological Health

BHB's Neuroprotective Effects

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The brain relies heavily on glucose as its primary energy source, but it can also utilize alternative fuels like ketone bodies, especially during times of glucose scarcity.[1] Ketones, including beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone (ACE), are produced in the liver through ketogenesis from acetyl-CoA, which is derived from fatty acid β-oxidation.[1] BHB is the most abundant ketone body in the blood.[1]

BHB has demonstrated neuroprotective effects through various mechanisms. It can serve as an alternative energy source for the brain, particularly in conditions of glucose deficit.[1] This is crucial because many neurological disorders are associated with impaired brain energy metabolism.[1]

BHB can also improve mitochondrial function. It can be converted to acetyl-CoA in mitochondria, producing NADH, which is essential for energy production.[1] BHB administration has been shown to improve mitochondrial respiration, particularly in complexes I and II, which are critical for ATP production.[1]

Exogenous Ketones and Therapeutic Potential

Furthermore, BHB exhibits antioxidant and anti-apoptotic properties. It can reduce oxidative stress and protect neurons from cell death.[1] This is achieved through various pathways, including the activation of signaling proteins and the upregulation of endogenous antioxidants.[1]

Given the benefits of BHB, exogenous ketone supplementation has emerged as a promising therapeutic strategy for neurological disorders.[1] Exogenous ketones (EKs) can induce ketosis regardless of dietary macronutrient intake.[1]

Potential Applications in Neurological Disorders

There are different types of EKs, including medium-chain triglycerides (MCTs), ketone salts, and ketone esters.[1] Ketone esters, such as (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (KME), are more potent and can elevate blood ketones to higher levels.[1]

BHB plays a crucial role in brain energy metabolism and exhibits neuroprotective effects. Exogenous ketone supplementation, particularly with ketone esters, holds promise as a therapeutic approach for various neurological disorders.

Conclusion

Ketosis induced by exogenous ketones may attenuate damage or improve cognitive and motor performance in neurological conditions such as seizure disorders, mild cognitive impairment, Alzheimer's disease, and neurotrauma.[1]

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