Therapeutic
ketosis is traditionally induced with
dietary modification. However, owing to the time delay involved, this is not a practical approach for treatment of acute conditions such as
traumatic brain injury.
Intravenous administration of
ketones would obviate this problem by rapidly inducing
ketosis. This has been confirmed in a number of small animal and human studies. Currently no such commercially available product exists. The aim of this systematic review is to review the safety and efficacy of intravenous
beta-hydroxybutyrate. The Web of Science, PubMed and EMBASE databases were searched, and a systematic review undertaken. Thirty-five studies were included. The total
beta-hydroxybutyrate dose ranged from 30 to 101 g administered over multiple doses as a short infusion, with most studies using the racemic form. Such dosing achieves a
beta-hydroxybutyrate concentration >1 mmol/L within 15 min. Infusions were well tolerated with few adverse events.
Blood glucose concentrations occasionally were reduced but remained within the normal reference range for all study participants. Few studies have examined the effect of intravenous
beta-hydroxybutyrate in disease states. In patients with
heart failure, intravenous
beta-hydroxybutyrate increased cardiac output by up to 40%. No studies were conducted in patients with neurological disease. Intravenous
beta-hydroxybutyrate has been shown to increase cerebral blood flow and reduce cerebral
glucose oxidation. Moreover,
beta-hydroxybutyrate reduces
protein catabolism and attenuates the production of counter-regulatory
hormones during induced
hypoglycemia. An intravenous
beta-hydroxybutyrate formulation is well tolerated and may provide an alternative treatment option worthy of further research in disease states.