Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy.
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.
Plecko
Barbara
B
Division of Metabolism and Pediatric Neurology, Department of Pediatrics, University Hospital of Graz, Austria.
Stoeckler-Ipsiroglu
Sylvia
S
Schober
Edith
E
Harrer
Georg
G
Mlynarik
Vladimir
V
Gruber
Stephan
S
Moser
Ewald
E
Moeslinger
Dorothea
D
Silgoner
Heinz
H
Ipsiroglu
Osman
O
D020155:3-Hydroxybutyric Acid / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D000284:Administration, Oral; D001786:Blood Glucose; D001923:Brain Chemistry; D019587:Dietary Supplements; D004562:Electrocardiography; D004569:Electroencephalography; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy*; D007003:Hypoglycemia / Q000188:drug therapy*; D007231:Infant, Newborn; D007657:Ketone Bodies / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D009682:Magnetic Resonance Spectroscopy; D018696:Neuroprotective Agents / Q000008:administration & dosage; D012008:Recurrence
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D018696:Neuroprotective Agents; D020155:3-Hydroxybutyric Acid