In
persistent hyperinsulinemic hypoglycemia of infancy,
ketone body concentrations are abnormally low at times of
hypoglycemia, depriving the brain of its most important alternative fuel. The
neuroprotective effect of endogenous
ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous
ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented DL
sodium beta-hydroxybutyrate (beta-OHB) in two 6-mo-old infants with
persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with
octreotide. Near total (95%)
pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of beta-OHB increased to levels comparable to a 16- to 24-h fast while on DL
sodium beta-OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of beta-OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of beta-OHB to
acetoacetate indicated exogenous origin of beta-OHB. An increase of intracerebral concentrations of beta-OHB could be demonstrated by repetitive single-voxel
proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral DL
sodium beta-OHB was tolerated without side effects. This first report on oral supplementation of DL
sodium beta-OHB in two patients with
persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood-brain barrier and could provide the basis for further evaluation of the
neuroprotective effect of beta-OHB in conditions with hypoketotic
hypoglycemia.