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Review
. 2011 Apr 6;15(2):219.
doi: 10.1186/cc10020.

Clinical review: ketones and brain injury

Affiliations
Review

Clinical review: ketones and brain injury

Hayden White et al. Crit Care. .

Abstract

Although much feared by clinicians, the ability to produce ketones has allowed humans to withstand prolonged periods of starvation. At such times, ketones can supply up to 50% of basal energy requirements. More interesting, however, is the fact that ketones can provide as much as 70% of the brain's energy needs, more efficiently than glucose. Studies suggest that during times of acute brain injury, cerebral uptake of ketones increases significantly. Researchers have thus attempted to attenuate the effects of cerebral injury by administering ketones exogenously. Hypertonic saline is commonly utilized for management of intracranial hypertension following cerebral injury. A solution containing both hypertonic saline and ketones may prove ideal for managing the dual problems of refractory intracranial hypertension and low cerebral energy levels. The purpose of the present review is to explore the physiology of ketone body utilization by the brain in health and in a variety of neurological conditions, and to discuss the potential for ketone supplementation as a therapeutic option in traumatic brain injury.

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Figures

Figure 1
Figure 1
Potential neuroprotective mechanisms of ketones. Ketones (1) require only three enzymatic steps to enter the tricarboxylic acid (TCA) cycle, (2) reduce the NAD couple, (3) decrease free radical formation, (4) increase production of ATP, (5) increase mitochondrial uncoupling, (6) increase glutathione peroxidase activity, and (7) inhibit pyruvate entry into the TCA cycle. CoA, coenzyme A; GSH, reduced glutathione; GSSG, oxidized glutathione; NAD+, nicotinamide adenine dinucleotide; NADH, nicotinamide adenine dinucleotide hydrogenase; NADP, nicotinamide adenine dinucleotide phosphate; NADPH, nicotinamide adenine dinucleotide phosphate hydrogenase; OHB, hydroxybutyrate; PPP, pentose phosphate pathway; UCP, uncoupling protein. Reprinted with permission from [43].

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